The Department of Energy`s Rocky Flats Plant: A guide to record series useful for health related research. Volume 4: Production and materials handling

This is the fourth in a series of seven volumes which constitute a guide to records of the Rocky Flats Plant useful for conducting health-related research. The primary purpose of Volume 4 is to describe record series pertaining to production and materials handling activities at the Department of Energy`s (DOE) Rocky Flats Plant, now named the Rocky Flats Environmental Technology Site, near Denver, Colorado. History Associates Incorporated (HAI) prepared this guide as part of its work as the support services contractor for DOE`s Epidemiologic Records Inventory Project. This introduction briefly describes the Epidemiologic Records Inventory Project and HAI`s role in the project, provides a history of production and materials handling practices at Rocky Flats, and identifies organizations contributing to production and materials handling policies and activities. Other topics include the scope and arrangement of the guide and the organization to contact for access to these records

Cardiac 123I-MIBG Scintigraphy in Neurodegenerative Parkinson Syndromes: Performance and Pitfalls in Clinical Practice

Purpose: Cardiac [123I]metaiodobenzylguanidine scintigraphy (123I-MIBG), reflecting postganglionic cardiac autonomic denervation, is proposed for early detection of Parkinson's disease (PD; reduced tracer uptake) and separation from Multiple System Atrophy (MSA; preserved tracer uptake). However, several recent studies report on frequent unexpected 123I-MIBG results in PD and MSA. We sought to determine, whether 123I-MIBG is feasible to discriminate PD from MSA in unselected geriatric patients in clinical practice.Materials and Methods: We screened consecutive patients, that underwent 123I-MIBG for diagnostic reasons. Delayed 123I-MIBG uptake (heart/mediastinum ratio; H/M ratio) was verified by clinical diagnosis of PD, MSA, and ET based on a two-stage clinical assessment: comprehensive baseline (including autonomic testing and additional neuroimaging) and confirmatory clinical follow-up.Results: 28 patients with clinical diagnosis of PD (N = 11), MSA (N = 9), and Essential Tremor (ET, N = 8) were identified. In one third (9/28) nuclear medical diagnosis deviated from clinically suspected syndrome. Visual interpretation of 123I-MIBG identified two cases (MSA and ET) with indeed normal 123I-MIBG uptake. Detailed review of clinical phenotypes provided only in two cases (PD and ET) an adequate explanation (correction of initial diagnosis and confounding drug history) for unexpected 123I-MIBG. In conclusion, 123I-MIBG did not match initial clinical phenotype in 27% PD, 44% MSA, and 25% ET patients.Conclusion: 123I-MIBG scintigraphy is a known specific and valuable technique in scientific approaches and well-defined and highly selected samples. However, predictability of 123I-MIBG based nuclear medical diagnosis for individual cases and thus, feasibility in routine clinical practice is limited. Our clinical series emphasize clinical verification of 123I-MIBG results on an individual basis in clinical routine

Pathophysiological mechanisms in Parkinson`s Disease and Dystonia – converging aetiologies

In this thesis I used a range of experimental approaches including genetics, enzyme activity measurements, histology and imaging to explore converging pathophysiological mechanisms of Parkinson`s disease and dystonia, two conditions with frequent clinical overlap. First, based on a combined retro- and prospective cohort of patients, using a combination of lysosomal enzyme activity measurements in peripheral blood and brain samples, as well as a target gene approach, I provide first evidence of reduced levels of enzyme activity in Glucocerebrosidase and the presence of GBA mutations, indicating lysosomal abnormality, in a relevant proportion of patients with dystonia of previously unknown origin. Second, based on a retrospective cohort of patients, I detail that a relevant proportion of genetically confirmed mitochondrial disease patients present with a movement disorder phenotype - predominantly dystonia and parkinsonism. Analysing volumetric MRI data, I describe a patterned cerebellar atrophy in these particular patients. This also includes the first cases of isolated dystonia due to mitochondrial disease, adding the latter as a potential aetiology for dystonia of unknown origin. Third, I used a combination of post-GWAS population genetic approaches and tissue-based experiments to explore in how far the strong association between advancing age and Parkinson ́s disease is mediated via telomere length. Although the initial finding of an association between genetically determined telomere length and PD risk did not replicate in independent cohorts, I provide evidence that telomere length in human putamen physiologically shortens with advancing age and 3 is regulated differently than in other brain regions. This is unique in the human brain, implying a particular age-related vulnerability of the striatum, part of the nigro-striatal network, crucially involved in PD pathophysiology. I conclude by discussing the above findings in light of the current literature, expand on their relevance and possible direction of future experiments

PROPOSED MIDDLEWARE SOLUTION FOR RESOURCE-CONSTRAINED DISTRIBUTED EMBEDDED NETWORKS

The explosion in processing power of embedded systems has enabled distributed embedded networks to perform more complicated tasks. Middleware are sets of encapsulations of common and network/operating system-specific functionality into generic, reusable frameworks to manage such distributed networks. This thesis will survey and categorize popular middleware implementations into three adapted layers: host-infrastructure, distribution, and common services. This thesis will then apply a quantitative approach to grading and proposing a single middleware solution from all layers for two target platforms: CubeSats and autonomous unmanned aerial vehicles (UAVs). CubeSats are 10x10x10cm nanosatellites that are popular university-level space missions, and impose power and volume constraints. Autonomous UAVs are similarly-popular hobbyist-level vehicles that exhibit similar power and volume constraints. The MAVLink middleware from the host-infrastructure layer is proposed as the middleware to manage the distributed embedded networks powering these platforms in future projects. Finally, this thesis presents a performance analysis on MAVLink managing the ARM Cortex-M 32-bit processors that power the target platforms

A Passage to Adulthood: Ethnographic perspectives on transitional care for adolescents with epilepsy and a comorbid learning disability

Transition is the planned and purposeful movement of adolescents with a chronic health condition into adult services. It aims to promote independence and self-management of young patients with regard to their ongoing health and care needs. However, particular challenges (including a reluctance of patients and families to leave the familiar paediatric environment and increased risk of psychological distress during the transitional period) have been identified as young patients move between these services. Consequently, this care practice has been identified as a key area for national improvement. In searching for ways to address these challenges, practitioners, researchers and policy makers have focused upon implementing care interventions that aim to build independence and responsibility amongst young patients. Given that young people who have epilepsy and severe forms of co-morbid learning disabilities [ELD] may not always reach complete independence from their carers, questions remain as to whether the aims of the transitional process are applicable to this population. Therefore, the aim of this thesis is to (re)specify the transition ‘challenge’ by documenting and analysing the institutional practices and lived experiences of ELD through a transitional care service. This study is the first to ethnographically examine the practice of UK transitional care for young people with ELD. Through a multi-sited ethnographic approach, I show that the transitional care between two hospitals in the north of England (and wider ‘social’ domains such as the family home and social care environments), is a highly situated and negotiated practice. Furthermore, narrative and observational methods of data collection with clinicians, care professionals, families and young people with ELD reveal transitional care to be a practice that is bound up with assumptions about what it means to be an adolescent, tensions in cultures of care, expectations regarding rites of passage and normative conceptualisations of the childhood-adulthood dichotomy. Based on these findings, the central argument of this thesis is that, whilst UK adolescent healthcare is a complex and contested care practice that organises and orders patients based on chronological age, it is also a social practice that operates in the context of wider political agendas and social ideals. In situating ELD transition within its institutional context, this study exposes the sociocultural arrangements that shape contemporary understandings and experiences of adolescence and disability. Crucially, it shows how society and culture shape biomedical practices and understandings of the adolescent patient

Clinicopathological characteristics of nigral neuron density in Lewy body spectrum diseases

Lewy body diseases are progressive neurodegenerative disorders that are clinically and pathologically heterogeneous. The combined base of the pathophysiology in Lewy body diseases is the pathological accumulation of α- synuclein, which forms Lewy bodies and Lewy neurites. The degeneration and Lewy pathology are particularly prominent in the substantia nigra, which is a crucial part of the dopaminergic system of the central nervous system. Lewy body disease patients usually have an individual spectrum of motor and nonmotor symptoms. The nonmotor symptoms, such as depression, may precede motor symptoms by several years. Substantial dopaminergic degeneration has already occurred by the time motor signs such as rigidity, bradykinesia and rest tremor emerge. The causative disease mechanism is unclear. Lewy body diseases decrease life quality and increase mortality. This thesis focuses on the relationships between degeneration of the dopaminergic nuclei and clinical features in Lewy body disease patients. Cases were collected from neuropathologic records of the University Hospital of Turku between 2002 and 2016 retrospectively and the corresponding clinical records were then reviewed. The association between Tyrosine hydroxylase positive substantia nigra neuron or putaminal axon numbers and striatal dopamine transporter binding, depressive symptoms and height were examined in Lewy body disease patients. The number of neurons and axons were counted manually using midbrain sections, and mathematical corrections were applied in the last two studies. The numbers of dopaminergic and tyrosine hydroxylase positive neurons in the substantia nigra or neurites in the striatum did not correlate with in vivo dopamine transporter binding. The results further demonstrate that neurodegeneration in the substantia nigra pars compacta in depressed Lewy body disease patients is more severe compared to non-depressed patients. The results also suggest that the height of Lewy body disease patients may be associated with neuron density in the substantia nigra pars compacta. These results shed light on some factors which underlie the large interindividual variability of substantia nigra pars compacta degeneration.Mustatumakkeen hermosolutiheyden kliinispatologiset piirteet Lewyn kappale -kertymäsairauksissa Lewyn kappale -kertymäsairaudet ovat heterogeenisia ja eteneviä hermostorappeumasairauksia. Näiden sairauksien yhteinen patofysiologinen piirre on α-synukleiinin kertyminen, mikä muodostaa Lewyn kappaleita ja Lewyn neuriitteja. Hermorappeuma ja Lewy-patologia ovat havaittavissa erityisesti mustatumakkeessa, joka on oleellinen osa keskushermoston dopaminergistä järjestelmää. Yleensä Lewyn kappale -kertymäsairaus potilaalla on yksilöllinen kirjo motorisia ja ei-motorisia oireita. Ei-motoriset oireet, kuten masennus, saattavat edeltää motorisia oireita useilla vuosilla. Motoristen oireiden, kuten jäykkyyden, hitauden ja lepovapinan, ilmetessä on havaittavissa jo merkittävää dopaminergisen hermoston rappeumaa. Taudin aiheuttava mekanismi on yhä epäselvä. Lewyn kappale -kertymäsairaudet alentavat potilaiden elämän laatua ja lisäävät kuolleisuutta. Tässä väitöstutkimuksessa keskityttiin dopaminergisten tyvitumakkeiden ja Lewyn kappale -kertymäsairauksien kliinisten piirteiden yhteyksiin. Potilastapaukset kerättiin Turun yliopistollisen sairaalan neuropatologian arkistoista 2002 ja 2006 välillä retrospektiivisesti. Kliininen data kerättiin vastaavasti potilastietojärjestelmistä. Tyrosiinihydroksylaasi positiivisten mustatumakkeiden hermosolujen tai putamenin aksonien määrän suhdetta aivojuovion dopamiinitransportterin sitoutumiseen, masennusoireisiin ja pituuteen tutkittiin Lewyn kappale -tautia sairastavilla potilailla. Hermosolujen ja aksonien määrä laskettiin manuaalisesti keskiaivoleikkeistä, ja matemaattista korjausta hyödynnettiin jälkimmäisissä tutkimuksissa. Tulokset osoittivat, että neuromelaniini- ja tyrosiinihydroksylaasipositiivisten mustatumakkeen hermosolujen ja aivokuorukan hermohaarakkeiden määrä ei korreloi dopamiinin takaisinottajan sitovuuteen. Lisäksi tulokset viittasivat siihen, että hermostorappeuma mustatumakkeessa on vaikeampaa masentuneilla kuin eimasentuneilla potilailla. Lisäksi vaikuttaa siltä, että aikuispituus saattaisi liittyä mustatumakkeen hermosolutiheyteen. Yhteenvedettynä tulokset auttavat ymmärtämään suurta yksilökohtaista vaihtelua mustatumakkeen hermorappeumassa, eli keskeisessä Lewyn kappale - kertymäsairauksien tautimekanismissa

A case study of professional development for history teachers in rural KwaZulu schools.

Thesis (M.Ed.)-University of Natal, Pietermaritzburg, 1996.The aim of the study was to report and evaluate a programme of teacher development in which the teachers themselves would be actively involved. A case study approach was adopted to monitor the programme of teacher development for history teachers within the context of six high schools in the rural area of Nongoma between July 1992 and December 1993. The teachers worked collectively in identifying, analysing and classifying the needs that were relevant to their particular circumstances. Teachers were observed in real classroom situations and commented on their experiences after working collectively. After being observed in real classroom situations teachers attempted to use teaching methods other than those they had been using before. Teaching methods attempted included group work, the skills-based approach and teaching for empathy. Recommendations were made for further teacher development. These included: putting time aside for professional development for such activities to be successful; assisting teachers during pre-service training to produce cheap teaching aids; and encouraging teachers to identify their needs in the field of professional development

Participatory crop improvement: the challenges of and opportunities for institutionalisation in the Indian public research sector

This thesis considers Participatory Crop Improvement (PCI) methodologies and examines the reasons behind their continued contestation and limited mainstreaming in conventional modes of crop improvement research within National Agricultural Research Systems (NARS). In particular, it traces the experiences of a long-established research network with over 20 years of experience in developing and implementing PCI methods across South Asia, and specifically considers its engagement with the Indian NARS and associated state-level agricultural research systems. In order to address the issues surrounding PCI institutionalisation processes, a novel conceptual framework was derived from a synthesis of the literatures on Strategic Niche Management (SNM) and Learning-based Development Approaches (LBDA) to analyse the socio-technical processes and structures which constitute the PCI ‘niche’ and NARS ‘regime’. In examining the niche and regime according to their socio-technical characteristics, the framework provides explanatory power for understanding the nature of their interactions and the opportunities and barriers that exist with respect to the translation of lessons and ideas between niche and regime organisations. The research shows that in trying to institutionalise PCI methods and principles within NARS in the Indian context, PCI proponents have encountered a number of constraints related to the rigid and hierarchical structure of the regime organisations; the contractual mode of most conventional research, which inhibits collaboration with a wider group of stakeholders; and the time-limited nature of PCI projects themselves, which limits investment and hinders scaling up of the innovations. It also reveals that while the niche projects may be able to induce a ‘weak’ form of PCI institutionalisation within the Indian NARS by helping to alter their institutional culture to be more supportive of participatory plant breeding approaches and future collaboration with PCI researchers, a ‘strong’ form of PCI institutionalisation, in which NARS organisations adopt participatory methodologies to address all their crop improvement agenda, is likely to remain outside of the capacity of PCI development projects to deliver