Development of an experimental setup for metal cutting research

Analytical, numerical and experimental models have been developed over time to try to characterize and understand the metal cutting process by chip removal. A true knowledge of the cutting process by chip removal is required by the increasing production, by the quality requirements of the product and by the reduced production time, in the industries in which it is employed. In this thesis an experimental setup is developed to evaluate the forces and the temperature distribution in the tool according to the orthogonal cutting model conditions, in order to evaluate its performance and its possible adoption in future works. The experimental setup is developed in a CNC lathe and uses an orthogonal cutting configuration, in which thin discs fixed onto a mandrel are cut by the cutting insert. In this experimental setup, the forces are measured by a piezoelectric dynamometer while temperatures are measured by thermocouples placed juxtaposed to the side face of the cutting insert. Three different solutions are implemented and evaluated for the thermocouples attachment in the cutting insert: thermocouples embedded in thermal paste, thermocouples embedded in copper plate and thermocouples brazed in the cutting insert. From the tests performed in the experimental setup it is concluded that the adopted forces measurement technique shows a good performance. Regarding to the adopted temperatures measurement techniques, only the thermocouples brazed in the cutting insert solution shows a good performance for temperature measurement. The remaining solutions show contact problems between the thermocouple and the side face of the cutting insert, especially when the vibration phenomenon intensifies during the cut. It is concluded that the experimental setup does not present a sufficiently robust and reliable performance, and that it can only be used in future work after making improvements in the assembly of the thermocouples.

Reinvigorating and redesigning early intervention in psychosis services for young people in Auckland

RESUMO: Auckland tem sido pioneira na implementação de modelos de Intervenção Precoce em Psicose. No entanto, esta organização do serviço não mudou nos últimos 19 anos. Segundo os dados obtidos da utilização do serviço, no período de 1996 -2012 foram atendidos 997 doentes, que tinham um número médio de 89 contactos (IQR: 36-184), com uma duração média de 62 horas de contactos (IQR: 24-136). Estes doentes passaram um número médio de 338 dias (IQR: 93-757) em contacto com o programa. 517 doentes (52%) não necessitaram de internamento no hospital, e os que foram internados, ficaram uma mediana de 124 dias no hospital (IQR: 40-380). Os doentes asiáticos tiveram um aumento de 50% de probabilidade de serem internados no hospital. Este relatório inclui 15 recomendações para orientar as reformas para o serviço e, nomeadamente, delinear a importância de uma visão organizacional e dos seus componentes-chave. As recomendações incluem o reforço da gestão e da liderança numa estrutura de equipe mais integrada, com recursos dedicados a melhorar a consciencialização da comunidade, a educação e deteção precoce, bem como a capacidade de receber referenciações diretas. Os Indicadores Chave de Desempenho devem ser estabelecidos, mas os Exames de Estado Mental em risco, devem ser removidos. Auckland deve manter a faixa etária alvo atual. A duração do serviço deve ser aumentada para um mínimo de três anos, com a opção de aumentá-la para cinco anos. A proporção de gestor de cuidados para os doentes deve ser preconizada em 1:15, enquanto o pessoal de apoio não-clínico deve ser aumentado. Os psiquiatras devem ter uma carga de trabalho de cerca de 80 doentes por equivalente de tempo completo. Um serviço local de prestação de cuidados deve ser desenvolvido com, nomeadamente, intervenções culturais para responder às necessidades da população multicultural de Auckland. A capacidade de investigação deve ser incorporada no Serviço de Intervenção Precoce em Psicoses. Qualquer alteração deverá envolver contacto com todas as partes interessadas, e a Administração Regional de Saúde deve comprometer-se em tempo, recursos humanos e políticos para apoiar e facilitar a mudança do sistema, investindo de forma significativa para melhor servir a comunidade Auckland.----------------------------------- ABSTRACT: Auckland has been pioneering in the adoption of Early Intervention in Psychosis models but the design of the service has not changed in 19 years. In service utilisation data from 997 patients seen from 1996 -2012, patients had a median number of 89 contacts (IQR: 36-184), with a median duration of 62 hours of contact (IQR: 24-136). Patients spent a median number of 338 days (IQR: 93-757) in contact with the program. 517 patients (52%) did not require admission to hospital, and those who did spent a median of 124 days in hospital (IQR: 40-380). Asian patients had a 50% increased chance of being admitted to hospital. This report includes 15 recommendations to guide reforms to the service, including outlining the importance of vision and key components. It recommends strengthened managerial leadership and a more integrated team structure with dedicated resources for improved community awareness, education and early detection as well as the capacity to take direct referrals. Key Performance Indicators (KPIs) should be established but At Risk Mental States should be excluded. Auckland should maintain the current target age range. The duration of service should be increased to a minimum of three years, with the option to extend this to five years. The ratio of care co-ordinator to patients should be capped at 1:15 whilst non-clinical supporting staff should be increased. Psychiatrists should have a caseload of about 80 per FTE. A local Service Delivery framework should be developed, as should cultural interventions to meet the needs of the multicultural population of Auckland. Research capacity should be incorporated into the fabric of Early Intervention in Psychosis Services. Any changes should involve consultation with all stakeholders, and the DHB should commit to investing time, human and political resources to support and facilitate meaningful system change to best serve the Auckland community.

Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.