The thalamus as a putative biomarker in neurodegenerative disorders

Objective: This review provides a brief account of the clinically relevant functional neuroanatomy of the thalamus, before considering the utility of various modalities utilised to image the thalamus and technical challenges therein, and going on to provide an overview of studies utilising structural imaging techniques to map thalamic morphology in the spectrum of neurodegenerative disorders. Methods: A systematic search was conducted for peer-reviewed studies involving structural neuroimaging modalities investigating the morphology (shape and/ or size) of the thalamus in the spectrum of neurodegenerative disorders. Results: Whilst the precise role of the thalamus in the healthy brain remains unclear, there is a large body of knowledge accumulating which defines more precisely its functional connectivity within the connectome, and a burgeoning literature implicating its involvement in neurodegenerative disorders. It is proposed that correlation of clinical features with thalamic morphology (as a component of a quantifiable subcortical connectome) will provide a better understanding of neuropsychiatric dysfunction in various neurodegenerative disorders, potentially yielding clinically useful endophenotypes and disease biomarkers. Conclusions: Thalamic biomarkers in the neurodegenerative disorders have great potential to provide clinically meaningful knowledge regarding not only disease onset and progression, but may yield targets of and perhaps a way of gauging response to future disease-modifying modalities

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

Apathy and Impulsivity in Frontotemporal Lobar Degeneration

Apathy and Impulsivity in Frontotemporal Lobar Degeneration Ian Coyle-Gilchrist Frontotemporal Lobar Degeneration (FTLD) is pathologically heterogeneous group of degenerative diseases of the brain. While there are distinct and highly recognisable clinical syndromes associated with FTLD there is also a wider and more diverse spectrum of progressive changes in movement, coordination, language and behaviour. Correlation between clinical syndrome and pathology is variable. Furthermore, over the course of an individual’s illness their syndrome may change, or they may present with features of more than one syndrome at a given time. Apathy and Impulsivity are common, distressing and disabling across the entire spectrum of FTLD and may be particularly prominent compared to other neurodegenerative diseases. In this thesis I outline the current classification of syndromes associated with FTLD and how this has undergone expansion, refinement and fragmentation over time. Despite changes in nosology and advances in understanding of pathological heterogeneity, I argue that the clinical syndrome of FTLD is highly recognisable and has been described for centuries. I suggest that a more unifying transdiagnostic approach to FTLD may provide useful insights into an increasingly fragmented spectrum of disease. Using this approach I conducted a large epidemiological study of FTLD and report prevalence, incidence and lifetime risk estimates. From this cohort of recruits I then surveyed patients and their carers and used a range of assessments of cognition and behaviour. I showed that while reports of apathy and impulsivity are common in FTLD, patient and carer based reports do not correlate well with each other or predict performance on a range of behavioural measures of decision making or goal directed cognition. I conclude that in FTLD, apathy and impulsivity are overlapping and multidimensional constructs and that no single testing modality used in isolation represents them completely, hence a multimodal approach to their assessment is required

Private sector participation in water provision : a reform policy to meet rapid growth and development, with reference to Arriyadh City, Saudi Arabia

PhD ThesisConstant increase in water demand, scarcity of resources, insufficient public finance, and the country's geographical position in one of the most and regions of the world have combined to create considerable problems in the provision of water to Saudi Arabia. This is in addition to the enormous and rapid increase in population growth, which is the main driver of demand and which was accompanied in the past by an increase in urbanisation, placing the country among the most highly urbanised countries. These conditions have instigated new patterns of demand that undermine the principle of sustainability. The high per capita consumption of water coupled with the low tariff levied by the government all represents a challenge for efficient management of water services around the country. As water provision in Saudi Arabia relies greatly upon government financing, any reduction of spending on the sector by the government is likely to mean shortage of supply and under-provision of services. The objective of this study is to increase the understanding of how the initial course of action might be explored, when seeking reform in order to promote private sector investment in the process of water services delivery. This entails potential, practicable reforms in the operation of the urban water system so as to put forward a model for such participation by the private sector, showing alternative long-term policies and institutional frameworks for the water industry and drawing key inferences concerning a new structure that will most benefit the country. Saudi Arabia is the case study, and its capital city Arriyadh is used as an example to show the impact of rapid growth upon water resources and services, and the associated implications. Basically, the case study is an intensive strategy used to access detailed knowledge in certain areas of science. To achieve the aims and objectives of this research, and to address its issues and questions a combination of primary and secondary procedures were employed to obtain the required knowledge, collection, analysis and interpretation of data. These include a literature survey, analysis of relevant documents, and focused interviews, as the objective was related to existing circumstances with a view to proposing new policies. This study finds that in the light of existing conditions, water demand will continue to increase due to projected population growth. This must mean the growing importance of seawater desalination in the future. Meeting demand with desalinated water entails new and significant expansion for the industry, and this will require vast investments which the government might not be able to provide. Given that, private sector involvement appears to offer a viable option for developing and running large-scale projects for water production. This study also indicates the importance of synchronised fundamental changes, with such participation including water tariff restructuring and effective control of network leakage, among others. Not surprisingly such changes in the water sector are both possible and expected, given the trend for this and other governments to increase the private sector's contribution to economic activities. The study offers a range of guiding principles that should be considered in line with the prospective changes in the country's water services. Finally, recommendations are made to support policy-makers in reaching appropriate decisions with respect to this vital resource, together with the intention of achieving greater sustainability in water development and management programmes

Insider Expungement

Like many phases of the criminal justice system, insiders dominate the practice of expungement and there is little to no involvement of the broader community. Recently, scholars in favor of democratization in criminal justice have called for enhanced public involvement during policing, charging, bail determinations, plea-bargaining, and sentencing to improve accountability, transparency, and democratic participation. This Article is the first to extend this critique to decision-making during the expungement process. It conveys how expungement always has been the province of insiders and how recent expungement reforms, while broadening some substantive expungement remedies, double down on this paradigm. Procedures are implemented by judicial staff, prosecutors and defense attorneys filter petitions, the ultimate decision usually rests with a single judge, and bureaucrats are tasked with making expungement efficacious. The move towards tech-based, automatic expungement is merely insider expungement by another name. After documenting insider expungement in its past and present forms, this Article explains why insider expungement adjudication is the norm. First, expungement processes were conceived, designed, and reformed in a system characterized by increased bureaucratization. In this sense, expungement law is a product of its environment. Second, the expungement remedy implicates the maintenance of public criminal records, which are connected to policy preferences for deterrence, incapacitation, and rehabilitation, all of which involve complicated costbenefit analyses. In the same vein, expungement adjudication is about the assignment of risk to individuals, which traditionally has been understood as the province of criminal justice experts. Finally, insider expungement is built on the premise that the public is too punitive. In sum, insider-based expungement is a product of forces for criminal justice professionalization that are larger than the field of expungement, as well as a belief that the public cannot be trusted to address stigma-based harm or foster reentry. Finally, while there is no question that the ability to obtain formal expungement relief has become easier over the past two decades, this Article notes several possible concerns with an exclusively insider-based expungement regime, including how secrecy and insider adjudication might undercut the purpose of expungement in the long run: full reintegration by the community and for more individuals. The absence of the community from expungement adjudication raises procedural justice, democratic, and legitimacy issues

Understanding the role of cholinergic tone in the pedunculopontine tegmental nucleus

Genetically modified mice targeting the vesicular acetylcholine transporter (VAChT) gene have been used as a tool to better understand the role of ACh signaling in specific regions of the brain (Prado et al., 2006; Guzman et al., 2011; de Castro et al., 2009). VAChT stores acetylcholine (ACh) in synaptic vesicles, and changes in this transporter expression directly interferes with ACh release. Here, we use a mouse line with VAChT deletion in the pedunculopontine tegmental nucleus (PPT) to evaluate the consequences of decreased cholinergic signaling from the PPT in vivo. Based on the efferent connectivity from the PPT, our hypothesis is that decreased cholinergic signaling from the PPT will affect specific behavioural outputs such as gait, motor control and sleep. Improving our understanding of cholinergic signaling from the PPT and how it relates to behavioural abnormalities may lead to the development of novel treatments for the symptoms of neurological diseases such as PD and PSP, which show degeneration of PPT neurons (Hirsch et al. 1987)

Minimizing storm water runoff from residential development through land use measures

This thesis is prepared from the perspective that development will continue to occur and that the trend for suburban land development will continue to be a primary housing source. The intent of this thesis is to suggest several land use ordinances that can help mitigate the impact of residential development if put into practice by a community

Amygdala subnuclei are differentially affected in the different genetic and pathological forms of frontotemporal dementia

Introduction Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with multiple genetic and pathological causes. It is characterized by both cortical and subcortical atrophies, with previous studies showing early involvement of the amygdala. However, no prior study has specifically investigated the atrophy of different subnuclei of the amygdala. Methods Using an automated segmentation tool for T1-weighted volumetric magnetic resonance imaging, we investigated amygdalar subnuclei (AS) involvement in a cohort of 132 patients with genetic or pathologically confirmed FTD (age: mean = 61 years (standard deviation = 8); disease duration: 5 (3) years) compared with 107 age-matched controls. Results AS were affected in all genetic and pathological forms of FTD. MAPT mutations/FTDP-17, Pick's disease, and transactive response DNA binding protein 43 kDa type C were the forms with the smallest amygdala (35%–50% smaller than controls in the most affected hemisphere, P < .0005). In most FTD groups, medial subnuclei (particularly the superficial, accessory basal and basal/paralaminar subnuclei) tended to be affected more than the lateral subnuclei, except for the progressive supranuclear palsy group, in which the corticoamygdaloid transition area was the least-affected area. Discussion Differential involvement of the AS was seen in the different genetic and pathological forms of FTD. In general, the most affected subnuclei were the superficial, accessory basal and basal/paralaminar subnuclei, which form part of a network of regions that control reward and emotion regulation, functions known to be particularly affected in FTD

Attracting private investment to the Caribbean water and sanitation sector

The investment needs of the water and sanitation sector and the financing constraints facing many developing countries were important catalysts for the promotion of private investment during the 1990s. Towards the end of the decade however, the flow of private capital began to decline primarily due to the poor performance of some investments and difficulties encountered during these transactions. Regardless, private investment is still considered an important financial resource for the sector which has resulted in considerable attention in addressing governance, economic and socio-political factors which can discourage investment. The aim of the research is to develop a strategic framework for attracting private investment to the Caribbean water and sanitation sector. Using a multiple-case study approach, the research examines the phenomenon of private investment in the water and sanitation sectors in Jamaica, Barbados and Trinidad and Tobago by assessing the environment for private investment and determining the specific drivers and deterrents to this type of investment. The implications of small size in the Caribbean context for institutional requirements to support private investment in the sector are also examined. Primary data for the research are obtained from public officials involved in the management, operation and regulation of the sector, local and international private service providers and local financial institutions through interviews and survey questionnaires. Documents are used to contextualise, corroborate and augment the research. The research found that in addition to traditional strategic and financial criteria in terms of provisions of the operating environment and investment performance, behaviour-related factors such as interest in job security, recognition and comfort were also important to the investment decision in the sector. Investors' perceptions of the utility were also found to be a statistically significant determinant of investment. Besides emphasising the importance of creating a conducive environment for investment, the research highlighted a need to simultaneously focus on generating specific investment opportunities to build investor confidence. The most important consequence of small size to negatively impact on creating conducive conditions for investment was the effect of limited professional capacity on institutional arrangements in the sector. Accordingly, sharing professional expertise to address capacity constraints emerged as the most feasible opportunity for regional cooperation to improve the environment for private investment in the sector

Design Techniques for Energy-Quality Scalable Digital Systems

Energy efficiency is one of the key design goals in modern computing. Increasingly complex tasks are being executed in mobile devices and Internet of Things end-nodes, which are expected to operate for long time intervals, in the orders of months or years, with the limited energy budgets provided by small form-factor batteries. Fortunately, many of such tasks are error resilient, meaning that they can toler- ate some relaxation in the accuracy, precision or reliability of internal operations, without a significant impact on the overall output quality. The error resilience of an application may derive from a number of factors. The processing of analog sensor inputs measuring quantities from the physical world may not always require maximum precision, as the amount of information that can be extracted is limited by the presence of external noise. Outputs destined for human consumption may also contain small or occasional errors, thanks to the limited capabilities of our vision and hearing systems. Finally, some computational patterns commonly found in domains such as statistics, machine learning and operational research, naturally tend to reduce or eliminate errors. Energy-Quality (EQ) scalable digital systems systematically trade off the quality of computations with energy efficiency, by relaxing the precision, the accuracy, or the reliability of internal software and hardware components in exchange for energy reductions. This design paradigm is believed to offer one of the most promising solutions to the impelling need for low-energy computing. Despite these high expectations, the current state-of-the-art in EQ scalable design suffers from important shortcomings. First, the great majority of techniques proposed in literature focus only on processing hardware and software components. Nonetheless, for many real devices, processing contributes only to a small portion of the total energy consumption, which is dominated by other components (e.g. I/O, memory or data transfers). Second, in order to fulfill its promises and become diffused in commercial devices, EQ scalable design needs to achieve industrial level maturity. This involves moving from purely academic research based on high-level models and theoretical assumptions to engineered flows compatible with existing industry standards. Third, the time-varying nature of error tolerance, both among different applications and within a single task, should become more central in the proposed design methods. This involves designing “dynamic” systems in which the precision or reliability of operations (and consequently their energy consumption) can be dynamically tuned at runtime, rather than “static” solutions, in which the output quality is fixed at design-time. This thesis introduces several new EQ scalable design techniques for digital systems that take the previous observations into account. Besides processing, the proposed methods apply the principles of EQ scalable design also to interconnects and peripherals, which are often relevant contributors to the total energy in sensor nodes and mobile systems respectively. Regardless of the target component, the presented techniques pay special attention to the accurate evaluation of benefits and overheads deriving from EQ scalability, using industrial-level models, and on the integration with existing standard tools and protocols. Moreover, all the works presented in this thesis allow the dynamic reconfiguration of output quality and energy consumption. More specifically, the contribution of this thesis is divided in three parts. In a first body of work, the design of EQ scalable modules for processing hardware data paths is considered. Three design flows are presented, targeting different technologies and exploiting different ways to achieve EQ scalability, i.e. timing-induced errors and precision reduction. These works are inspired by previous approaches from the literature, namely Reduced-Precision Redundancy and Dynamic Accuracy Scaling, which are re-thought to make them compatible with standard Electronic Design Automation (EDA) tools and flows, providing solutions to overcome their main limitations. The second part of the thesis investigates the application of EQ scalable design to serial interconnects, which are the de facto standard for data exchanges between processing hardware and sensors. In this context, two novel bus encodings are proposed, called Approximate Differential Encoding and Serial-T0, that exploit the statistical characteristics of data produced by sensors to reduce the energy consumption on the bus at the cost of controlled data approximations. The two techniques achieve different results for data of different origins, but share the common features of allowing runtime reconfiguration of the allowed error and being compatible with standard serial bus protocols. Finally, the last part of the manuscript is devoted to the application of EQ scalable design principles to displays, which are often among the most energy- hungry components in mobile systems. The two proposals in this context leverage the emissive nature of Organic Light-Emitting Diode (OLED) displays to save energy by altering the displayed image, thus inducing an output quality reduction that depends on the amount of such alteration. The first technique implements an image-adaptive form of brightness scaling, whose outputs are optimized in terms of balance between power consumption and similarity with the input. The second approach achieves concurrent power reduction and image enhancement, by means of an adaptive polynomial transformation. Both solutions focus on minimizing the overheads associated with a real-time implementation of the transformations in software or hardware, so that these do not offset the savings in the display. For each of these three topics, results show that the aforementioned goal of building EQ scalable systems compatible with existing best practices and mature for being integrated in commercial devices can be effectively achieved. Moreover, they also show that very simple and similar principles can be applied to design EQ scalable versions of different system components (processing, peripherals and I/O), and to equip these components with knobs for the runtime reconfiguration of the energy versus quality tradeoff