Derivation and consistency checking of models in early software product line engineering

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

Transimpedance amplifier for early detection of breast cancer

Breast cancer is the most common type of cancer worldwide. The effectiveness of its treatment depends on early stage detection, as well as on the accuracy of its diagnosis. Recently, diagnosis techniques have been submitted to relevant breakthroughs with the upcoming of Magnetic Resonance Imaging, Ultrasound Sonograms and Positron Emission Tomography (PET) scans, among others. The work presented here is focused on studying the application of a PET system to a Positron Emission Mammography (PEM) system. A PET/PEM system works under the principle that a scintillating crystal will detect a gamma-ray pulse, originated at the cancerous cells, converting it into a correspondent visible light pulse. The latter must then be converted into an electrical current pulse by means of a Photo- -Sensitive Device (PSD). After the PSD there must be a Transimpedance Amplifier (TIA) in order to convert the current pulse into a suitable output voltage, in a time period lower than 40 ns. In this Thesis, the PSD considered is a Silicon Photo-Multiplier (SiPM). The usage of this recently developed type of PSD is impracticable with the conventional TIA topologies, as it will be proven. Therefore, the usage of the Regulated Common-Gate (RCG) topology will be studied in the design of the amplifier. There will be also presented two RCG variations, comprising a noise response improvement and differential operation of the circuit. The mentioned topology will also be tested in a Radio-Frequency front-end, showing the versatility of the RCG. A study comprising a low-voltage self-biasing feedback TIA will also be shown. The proposed circuits will be simulated with standard CMOS technology (UMC 130 nm), using a 1.2 V power supply. A power consumption of 0.34 mW with a signal-to-noise ratio of 43 dB was achieved.

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.

Experimental design methodologies for the identification of Michaelis-Menten type kinetics

The main objective of this work was to investigate the application of experimental design techniques for the identification of Michaelis-Menten kinetic parameters. More specifically, this study attempts to elucidate the relative advantages/disadvantages of employing complex experimental design techniques in relation to equidistant sampling when applied to different reactor operation modes. All studies were supported by simulation data of a generic enzymatic process that obeys to the Michaelis-Menten kinetic equation. Different aspects were investigated, such as the influence of the reactor operation mode (batch, fed-batch with pulse wise feeding and fed-batch with continuous feeding) and the experimental design optimality criteria on the effectiveness of kinetic parameters identification. The following experimental design optimality criteria were investigated: 1) minimization of the sum of the diagonal of the Fisher information matrix (FIM) inverse (A-criterion), 2) maximization of the determinant of the FIM (D-criterion), 3) maximization of the smallest eigenvalue of the FIM (E-criterion) and 4) minimization of the quotient between the largest and the smallest eigenvalue (modified E-criterion). The comparison and assessment of the different methodologies was made on the basis of the Cramér-Rao lower bounds (CRLB) error in respect to the parameters vmax and Km of the Michaelis-Menten kinetic equation. In what concerns the reactor operation mode, it was concluded that fed-batch (pulses) is better than batch operation for parameter identification. When the former operation mode is adopted, the vmax CRLB error is lowered by 18.6 % while the Km CRLB error is lowered by 26.4 % when compared to the batch operation mode. Regarding the optimality criteria, the best method was the A-criterion, with an average vmax CRLB of 6.34 % and 5.27 %, for batch and fed-batch (pulses), respectively, while presenting a Km’s CRLB of 25.1 % and 18.1 %, for batch and fed-batch (pulses), respectively. As a general conclusion of the present study, it can be stated that experimental design is justified if the starting parameters CRLB errors are inferior to 19.5 % (vmax) and 45% (Km), for batch processes, and inferior to 42 % and to 50% for fed-batch (pulses) process. Otherwise equidistant sampling is a more rational decision. This conclusion clearly supports that, for fed-batch operation, the use of experimental design is likely to largely improve the identification of Michaelis-Menten kinetic parameters.

A new wader, Recurvirostridae (Charadriiformes), from the early Eocene of Portugal

A new wader (Aves, Charadriiformes, Recurvirostridae) from the Early Eocene site of Silveirinha, in Lower Mondego region, Central Portugal, is described. Comparisons have been made with other forms, both extant and fossil; its affmities are discussed. Silveirinha wader is ascribed to Fluviatilavis antunesi, n. gen. n. sp.