Homeopatia em Pediatria

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Nanopartículas e suas aplicações em Ciências Farmacêuticas

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Patient-centred screening for primary immunodeficiency: a multi-stage diagnostic protocol designed for non-immunologists.

Efficient early identification of primary immunodeficiency disease (PID) is important for prognosis, but is not an easy task for non-immunologists. The Clinical Working Party of the European Society for Immunodeficiencies (ESID) has composed a multi-stage diagnostic protocol that is based on expert opinion, in order to increase the awareness of PID among doctors working in different fields. The protocol starts from the clinical presentation of the patient; immunological skills are not needed for its use. The multi-stage design allows cost-effective screening for PID within the large pool of potential cases in all hospitals in the early phases, while more expensive tests are reserved for definitive classification in collaboration with an immunologist at a later stage. Although many PIDs present in childhood, others may present at any age. The protocols presented here are therefore aimed at both adult physicians and paediatricians. While designed for use throughout Europe, there will be national differences which may make modification of this generic algorithm necessary.

Monte Carlo Analysis and Physics Characterization of a Novel Nanoparticle Detector for Medical and Micro-dosimetry Applications

The outcomes for both (i) radiation therapy and (ii) preclinical small animal radio- biology studies are dependent on the delivery of a known quantity of radiation to a specific and intentional location. Adverse effects can result from these procedures if the dose to the target is too high or low, and can also result from an incorrect spatial distribution in which nearby normal healthy tissue can be undesirably damaged by poor radiation delivery techniques. Thus, in mice and humans alike, the spatial dose distributions from radiation sources should be well characterized in terms of the absolute dose quantity, and with pin-point accuracy. When dealing with the steep spatial dose gradients consequential to either (i) high dose rate (HDR) brachytherapy or (ii) within the small organs and tissue inhomogeneities of mice, obtaining accurate and highly precise dose results can be very challenging, considering commercially available radiation detection tools, such as ion chambers, are often too large for in-vivo use.

In this dissertation two tools are developed and applied for both clinical and preclinical radiation measurement. The first tool is a novel radiation detector for acquiring physical measurements, fabricated from an inorganic nano-crystalline scintillator that has been fixed on an optical fiber terminus. This dosimeter allows for the measurement of point doses to sub-millimeter resolution, and has the ability to be placed in-vivo in humans and small animals. Real-time data is displayed to the user to provide instant quality assurance and dose-rate information. The second tool utilizes an open source Monte Carlo particle transport code, and was applied for small animal dosimetry studies to calculate organ doses and recommend new techniques of dose prescription in mice, as well as to characterize dose to the murine bone marrow compartment with micron-scale resolution.

Hardware design changes were implemented to reduce the overall fiber diameter to <0.9 mm for the nano-crystalline scintillator based fiber optic detector (NanoFOD) system. Lower limits of device sensitivity were found to be approximately 0.05 cGy/s. Herein, this detector was demonstrated to perform quality assurance of clinical 192Ir HDR brachytherapy procedures, providing comparable dose measurements as thermo-luminescent dosimeters and accuracy within 20% of the treatment planning software (TPS) for 27 treatments conducted, with an inter-quartile range ratio to the TPS dose value of (1.02-0.94=0.08). After removing contaminant signals (Cerenkov and diode background), calibration of the detector enabled accurate dose measurements for vaginal applicator brachytherapy procedures. For 192Ir use, energy response changed by a factor of 2.25 over the SDD values of 3 to 9 cm; however a cap made of 0.2 mm thickness silver reduced energy dependence to a factor of 1.25 over the same SDD range, but had the consequence of reducing overall sensitivity by 33%.

For preclinical measurements, dose accuracy of the NanoFOD was within 1.3% of MOSFET measured dose values in a cylindrical mouse phantom at 225 kV for x-ray irradiation at angles of 0, 90, 180, and 270˝. The NanoFOD exhibited small changes in angular sensitivity, with a coefficient of variation (COV) of 3.6% at 120 kV and 1% at 225 kV. When the NanoFOD was placed alongside a MOSFET in the liver of a sacrificed mouse and treatment was delivered at 225 kV with 0.3 mm Cu filter, the dose difference was only 1.09% with use of the 4x4 cm collimator, and -0.03% with no collimation. Additionally, the NanoFOD utilized a scintillator of 11 µm thickness to measure small x-ray fields for microbeam radiation therapy (MRT) applications, and achieved 2.7% dose accuracy of the microbeam peak in comparison to radiochromic film. Modest differences between the full-width at half maximum measured lateral dimension of the MRT system were observed between the NanoFOD (420 µm) and radiochromic film (320 µm), but these differences have been explained mostly as an artifact due to the geometry used and volumetric effects in the scintillator material. Characterization of the energy dependence for the yttrium-oxide based scintillator material was performed in the range of 40-320 kV (2 mm Al filtration), and the maximum device sensitivity was achieved at 100 kV. Tissue maximum ratio data measurements were carried out on a small animal x-ray irradiator system at 320 kV and demonstrated an average difference of 0.9% as compared to a MOSFET dosimeter in the range of 2.5 to 33 cm depth in tissue equivalent plastic blocks. Irradiation of the NanoFOD fiber and scintillator material on a 137Cs gamma irradiator to 1600 Gy did not produce any measurable change in light output, suggesting that the NanoFOD system may be re-used without the need for replacement or recalibration over its lifetime.

For small animal irradiator systems, researchers can deliver a given dose to a target organ by controlling exposure time. Currently, researchers calculate this exposure time by dividing the total dose that they wish to deliver by a single provided dose rate value. This method is independent of the target organ. Studies conducted here used Monte Carlo particle transport codes to justify a new method of dose prescription in mice, that considers organ specific doses. Monte Carlo simulations were performed in the Geant4 Application for Tomographic Emission (GATE) toolkit using a MOBY mouse whole-body phantom. The non-homogeneous phantom was comprised of 256x256x800 voxels of size 0.145x0.145x0.145 mm3. Differences of up to 20-30% in dose to soft-tissue target organs was demonstrated, and methods for alleviating these errors were suggested during whole body radiation of mice by utilizing organ specific and x-ray tube filter specific dose rates for all irradiations.

Monte Carlo analysis was used on 1 µm resolution CT images of a mouse femur and a mouse vertebra to calculate the dose gradients within the bone marrow (BM) compartment of mice based on different radiation beam qualities relevant to x-ray and isotope type irradiators. Results and findings indicated that soft x-ray beams (160 kV at 0.62 mm Cu HVL and 320 kV at 1 mm Cu HVL) lead to substantially higher dose to BM within close proximity to mineral bone (within about 60 µm) as compared to hard x-ray beams (320 kV at 4 mm Cu HVL) and isotope based gamma irradiators (137Cs). The average dose increases to the BM in the vertebra for these four aforementioned radiation beam qualities were found to be 31%, 17%, 8%, and 1%, respectively. Both in-vitro and in-vivo experimental studies confirmed these simulation results, demonstrating that the 320 kV, 1 mm Cu HVL beam caused statistically significant increased killing to the BM cells at 6 Gy dose levels in comparison to both the 320 kV, 4 mm Cu HVL and the 662 keV, 137Cs beams.

A Kinect Based Indoor Navigation System for the Blind

Team NAVIGATE aims to create a robust, portable navigational aid for the blind. Our prototype uses depth data from the Microsoft Kinect to perform realtime obstacle avoidance in unfamiliar indoor environments. The device augments the white cane by performing two signi cant functions: detecting overhanging objects and identifying stairs. Based on interviews with blind individuals, we found a combined audio and haptic feedback system best for communicating environmental information. Our prototype uses vibration motors to indicate the presence of an obstacle and an auditory command to alert the user to stairs ahead. Through multiple trials with sighted and blind participants, the device was successful in detecting overhanging objects and approaching stairs. The device increased user competency and adaptability across all trials.

La Mancha Triassic and Lower Lias Stratigraphy, a well log interpretation

La estratigrafía del intervalo sedimentario correspondiente al Keuper, Triásico, y al Lías basal ha atraído históricamente mucho menos interés que los sedimentos adyacentes del Muschelkalk y Buntsandstein, y del Lías Inferior y Medio. Se ha confeccionado una correlación de 12 sondeos profundos del área de La Mancha para mostrar la distribución de facies de estas formaciones, así como su ordenación en secuencias sedimentarias. Los datos de pozo muestran la existencia de secuencias evaporíticas complejas y multiepisódicas en la unidad inferior K1, de carácter más salino, y en la unidad superior K4-K5, relativamente más anhidrítica. El episodio clástico correspondiente a las unidades K2-K3 está extendido en toda la zona, con varias áreas preferenciales de acumulación de arenas. La unidad K6, la más alta del Keuper, constituye un excelente nivel guía. La sedimentación continúa en el Lías basal con otra potente unidad evaporítica, la Zona de Anhidrita, que muestra un episodio salino muy signifi cativo en la parte central de la correlación. Es de resaltar la buena correlación que existe entre los afl oramientos y las sondeos para estas formaciones.

Piornales, enebrales y pinares oromediterráneos (Pino-Cytision oromediterranei) en el Sistema Central

Se revisan fitosociológicamente los bosques y matorrales oromediterráneos del Sistema Central pertenecientes a la alianza Pino-Cytision oromediterranei. Un suborden, una asociación y seis subasociaciones se proponen como nuevos: Juniperenalia nanae, Echinosparto pulviniformis-Cytisetum oromediterranei, Cytiso-Echinospartetum barnadesii ericetsoum arboreae, Junipero-Cytisetum oromediterranei adenocarpetosum hispanici, arctostaphylletosum crassifoliae, ericetosum aragonensis, genistetosum cinerascentis y populetosum tremulae. Asimismo, se proponen diversas correcciones nomenclaturales y se tipifican los principales sintáxones de la clase. Por último, se presenta un esquema sintaxonómico de la misma en la Península Ibérica hasta el nivel de asociación, con la diagnosis biogeográfica, ecológica y florística de los sintáxones de rango superior.Finalmente, en el apéndice florístico se proponen tres nuevas combinaciones nomenclaturales: Echinospartum ibericum Rivas-Martínez, Sánchez-Mata & Sancho, E. ibericum subsp. pulviniformis (Rivas-Martínez) Rivas-Martínez y Thymus praecox Opiz subsp. penyalarensis (Pau) Rivas-Martínez, Fernández-González & Sánchez-Mata.

Datos sobre la vegetación de las Sierras de Guadarrama y Malagón

Se revisan los sintaxones representados en la Sierra de Malagón y sector occidental de la Sierra de Guadarrama pertenecientes a las clases: Pino-Juniperetea, Cytisetea scopario-striati, Cisto-Lavanduletea y Sedo-Scleranthetea. Se describen un orden, una alianza, tres asociaciones y cinco subasoc¡aciones, asimismo se proponen dos combinaciones sintaxonómicas.

Revisión del género Serratula L. (Asteraceae) en la Península Ibérica

Se ha realizado la revisión del género Serratula L. en la Península Ibérica. Se reconocen quince táxones, distribuidos en siete especies y dos secciones. Se incluye una clave para la determinación dc las especies. Para cada taxon se indica el nombre correcto, sinonimias, tipo y tipos de sinónimos taxonómicos cuando han sido estodiados, descripción, número cromosómico, corología. ecología y fitosociología.

Datos sobre la vegetación del valle del río Bidasoa (España)

Se hace una descripción de las cinco series de vegetación que constituyen el paisaje vegetal de la cuenca del rio Bidasoa en Navarra (norte de España) y se aportan tablas fitosocíologicas de las comunidades que representan la etapa madura de cada serie asi como una tabla de los brezale sdel territorio. Se describen en ellas dos nuevas subasociaciones Polytricho setiferi-Fraxinetum excelsioris carpinetosum betuli y Tamo communis-Quercetum roboris fagetosum sylvticae.

Comentarios sobre la flora y vegetación de la Sierra de Alcaraz, (Albacete, España)

Sc comentan aspectos geobotánicos y algunos táxones interesantes de la Siena de Alcaraz (Albacete, España), sector Subbético, provincia corológica Bética. En esta nota se tratan fundamentalmente los matorrales de la alianza Lavandulo-Echinospartion boissieri comprendidos en el tramo serrano Riópar-Vianos.

Combinationes novae in Klasea Cass. (Asteraceae)

Se proponen seis nuevas combinaciones en el género Klasea Cass.

Números cromosómicos en algunos taxones del género Serratula L. (Asteraceae)

Se estudian 44 poblaciones de 7 táxones ibéricos del género Serratula L. Se obtienen como resultado los números cromosomáticos siguientes: S. tinctoria L., 2n=22; S. nudicaulis (L.) DC., 2n= 30 + (0-4) B; S. flavescens (L.) Poiret subsp. flavescens, 2n=30; S. flavescens subsp. leucantha (Cav.) Cant�� & Costa stat. nov., 2n=30; S. flavescens subsp. mucronata (Desf.) Cant�� stat. nov., 2n=60; S. pinnatifida (Cav.) Poiret, 2n=60, 90; S. legionensis Lacaita, 2n=30.

Lectotipificación de Serratula monardii Duf. (Asteraceae)

En la presente comunicación se lectotipifica S. monardii Duf.

Serratula baetica Boiss. subsp. lusitanica (Asteraceae) subsp. nova

Se describe un nuevo taxon para Portugal: Serratula baetica Boiss. subsp. lusitanica Cant��, subsp. nova.