Implementation of a new reference values database for semiquantification in123I-FP-CIT brain single emission tomography

Brain dopamine transporters imaging by Single Emission Tomography (SPECT) with 123I-FP-CIT (DaTScanTM) has become an important tool in the diagnosis and evaluation of Parkinson syndromes.This diagnostic method allows the visualization of a portion of the striatum – where healthy pattern resemble two symmetric commas - allowing the evaluation of dopamine presynaptic system, in which dopamine transporters are responsible for dopamine release into the synaptic cleft, and their reabsorption into the nigrostriatal nerve terminals, in order to be stored or degraded. In daily practice for assessment of DaTScan TM, it is common to rely only on visual assessment for diagnosis. However, this process is complex and subjective as it depends on the observer’s experience and it is associated with high variability intra and inter observer. Studies have shown that semiquantification can improve the diagnosis of Parkinson syndromes. For semiquantification, analysis methods of image segmentation using regions of interest (ROI) are necessary. ROIs are drawn, in specific - striatum - and in nonspecific – background – uptake areas. Subsequently, specific binding ratios are calculated. Low adherence of semiquantification for diagnosis of Parkinson syndromes is related, not only with the associated time spent, but also with the need of an adapted database of reference values for the population concerned, as well as, the examination of each service protocol. Studies have concluded, that this process increases the reproducibility of semiquantification. The aim of this investigation was to create and validate a database of healthy controls for Dopamine transporters with DaTScanTM named DBRV. The created database has been adapted to the Nuclear Medicine Department’s protocol, and the population of Infanta Cristina’s Hospital located in Badajoz, Spain.

Validation of a new reference values’s database for semiquantification of 123I‐FP‐CIT SPECT scans in one nuclear medicine department

The DatScanTM and its Semiquantification (SQ) can provide advantages in the diagnosis of Parkinsonian Syndromes (PS). To improve the SQ is recommended the creation of adapted database (DB) with reference values for the Nuclear Medicine Departments. Previously to this work was created a adapted database (DBRV) to Nuclear Medicine Department's protocol and population of Infanta Cristina's Hospital located in Badajoz, for patients between the ages of 60 and 75, and reference values of the SQ were calculated. Aim: To evaluate the discrimination capacity of a department's adapted DB reference's values of healthy controls for DatScanTM.

Clinical classification versus semiquantification with adapted reference values for 123I-FP-CIT SPECT in a nuclear medicine department

Semi quantification (SQ) in DaTScan® studies is broadly used in clinic daily basis, however there is a suspicious about its discriminative capability, and concordance with the diagnostic classification performed by the physician. Aim: Evaluate the discriminate capability of an adapted database and reference's values of healthy controls for the Dopamine Transporters (DAT) with 123I–FP-IT named DBRV adapted to Nuclear Medicine Department's protocol and population of Infanta Cristina's Hospital, and its concordance with the physician classification.

Criação e validação de valores de referência para semiquantificação em exames de SPECT com 123I-FP- CIT para o Hospital Infanta Cristina em Badajoz

Semiquantificação (SQ) nos exames de O DaTScanTM pode apresentar vantagens no diagnóstico de Síndromes Parkinsonianos (SP), especialmente quando os valores utilizados para referência da SQ são adaptados ao serviço em causa. Objetivo do estudo - Criação e validação de bases de dados e valores de referência (VR) adaptados na SQ para diagnóstico de SP recorrendo ao de DaTScanTM, adaptados para o Hospital Infanta Cristina em Badajoz.

Uniformidade de massa no fraccionamento de comprimidos de varfarina

Apesar da importância reconhecida da dispensa de medicamentos em unidose a nível hospitalar, em determinadas situações as apresentações comerciais disponíveis não oferecem alternativa à terapêutica desejada. Deste modo, surge por parte dos Serviços Farmacêuticos Hospitalares a necessidade de proceder à manipulação de alguns medicamentos. Uma dessas situações prende-se com a necessidade de fraccionamento de algumas formas orais sólidas. Todavia, embora o fraccionamento de comprimidos seja uma prática frequente, não só para obter doses não comercializadas como também para permitir titular o regime posológico ou facilitar a deglutição, este nem sempre é recomendável. Um dos problemas associados ao fraccionamento de comprimidos prende-se com as perdas com possam ocorrer durante o processo, levando a que a dosagem efectivamente dispensada não seja coincidente com a efectivamente esperada. Segundo a Farmacopeia Portuguesa (FP VIII), em comprimidos com massa até 80 mg, após pesagem de 20 unidades e determinação do seu peso médio, não mais de 2 unidades podem afastar-se 10% do peso médio e nenhuma unidade se pode afastar mais de 20%. Assim sendo, tal condição assume particular importância quando se procede ao fraccionamento de medicamentos contendo fármacos com margem terapêutica estreita. Um desses casos associa-se à varfarina. Usada como anticoagulante oral, a varfarina é comercializada em comprimidos com uma dosagem de 5 mg. A sua dose inicial em adultos é habitualmente de 10 mg diários durante dois dias, sendo a dose de manutenção dependente do tempo de protrombina. Deste modo, a dose de manutenção pode alcançar dosagens não comercializadas, tais como 1,25 mg e 2,5 mg. No Centro Hospitalar de São João, EPE, o fraccionamento de comprimidos de varfarina 5 mg tem constituído uma prática frequente, com cerca de 132 unidades fraccionadas a 2,5 mg e 20 unidades fraccionadas a 1,25 mg, durante o ano de 2010. Todavia, a falta de estudos publicados que comprovem a segurança da uniformidade de massa após o fraccionamento deste medicamento colocam ainda algumas questões. Este trabalho pretende assim avaliar a uniformidade das fracções obtidas após fraccionamento dos comprimidos de varfarina, com o intuito de conhecer se estes se encontram dentro dos parâmetros estabelecidos pela FP VIII.

DRhoGEF2 regulates cellular tension and cell pulsations in the Amnioserosa during Drosophila dorsal closure

Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction.

Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that together efficiently interact with and dissociate the tubulin dimer. In the study reported here we showed that TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO− present in TBCB, which is similar to the EEY/F-COO− element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated with microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation.

Anomaly-free U(1) gauge symmetries in neutrino seesaw flavor models

Agência Financiadora: Fundação para a Ciência e a Tecnologia (FCT) - PEst-OE/FIS/UI0777/2013; CERN/FP/123580/2011; PTDC/FIS-NUC/0548/2012

PET/CT com 18-fluor-fluorodeoxiglucose no seguimento do melanoma maligno cutâneo

Introdução – O melanoma maligno cutâneo (MMC) é considerado uma das mais letais neoplasias e no seu seguimento recorre-se, para além dos exames clínicos e da análise de marcadores tumorais, a diversos métodos imagiológicos, como é o exame Tomografia por Emissão de Positrões/Tomografia Computorizada (PET/CT, do acrónimo inglês Positron Emission Tomography/Computed Tomography) com 18fluor-fluorodeoxiglucose (18F-FDG). O presente estudo tem como objetivo avaliar a utilidade da PET/CT relativamente à análise da extensão e à suspeita de recidiva do MMC, comparando os achados imagiológicos com os descritos em estudos CT. Metodologia – Estudo retrospetivo de 62 estudos PET/CT realizados em 50 pacientes diagnosticados com MMC. Excluiu-se um estudo cujo resultado era duvidoso (nódulo pulmonar). As informações relativas aos resultados dos estudos anatomopatológicos e dos exames imagiológicos foram obtidas através da história clínica e dos relatórios médicos dos estudos CT e PET/CT. Foi criada uma base de dados com os dados recolhidos através do software Excel e foi efetuada uma análise estatística descritiva. Resultados – Dos estudos PET/CT analisados, 31 foram considerados verdadeiros positivos (VP), 28 verdadeiros negativos (VN), um falso positivo (FP) e um falso negativo (FN). A sensibilidade, especificidade, o valor preditivo positivo (VPP), o valor preditivo negativo (VPN) e a exatidão da PET/CT para o estadiamento e avaliação de suspeita de recidiva no MMC são, respetivamente, 96,9%, 96,6%, 96,9%, 96,6% e 96,7%. Dos resultados da CT considerados na análise estatística, 14 corresponderam a VP, 12 a VN, três a FP e cinco a FN. A sensibilidade, especificidade, o VPP e o VPN e a exatidão da CT para o estadiamento e avaliação de suspeita de recidiva no MMC são, respetivamente, 73,7%, 80,0%, 82,4%, 70,6% e 76,5%. Comparativamente aos resultados CT, a PET/CT permitiu uma mudança na atitude terapêutica em 23% dos estudos. Conclusão – A PET/CT é um exame útil na avaliação do MMC, caracterizando-se por uma maior acuidade diagnóstica no estadiamento e na avaliação de suspeita de recidiva do MMC comparativamente à CT isoladamente.

Assessment of the quality of brain regions and neuroimaging metrics as biomarkers of Alzheimer’s disease

Alzheimer Disease (AD) is characterized by progressive cognitive decline and dementia. Earlier diagnosis and classification of different stages of the disease are currently the main challenges and can be assessed by neuroimaging. With this work we aim to evaluate the quality of brain regions and neuroimaging metrics as biomarkers of AD. Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox functionalities were used to study AD by T1weighted, Diffusion Tensor Imaging and 18FAV45 PET, with data obtained from the AD Neuroimaging Initiative database, specifically 12 healthy controls (CTRL) and 33 patients with early mild cognitive impairment (EMCI), late MCI (LMCI) and AD (11 patients/group). The metrics evaluated were gray-matter volume (GMV), cortical thickness (CThk), mean diffusivity (MD), fractional anisotropy (FA), fiber count (FiberConn), node degree (Deg), cluster coefficient (ClusC) and relative standard-uptake-values (rSUV). Receiver Operating Characteristic (ROC) curves were used to evaluate and compare the diagnostic accuracy of the most significant metrics and brain regions and expressed as area under the curve (AUC). Comparisons were performed between groups. The RH-Accumbens/Deg demonstrated the highest AUC when differentiating between CTRLEMCI (82%), whether rSUV presented it in several brain regions when distinguishing CTRL-LMCI (99%). Regarding CTRL-AD, highest AUC were found with LH-STG/FiberConn and RH-FP/FiberConn (~100%). A larger number of neuroimaging metrics related with cortical atrophy with AUC>70% was found in CTRL-AD in both hemispheres, while in earlier stages, cortical metrics showed in more confined areas of the temporal region and mainly in LH, indicating an increasing of the spread of cortical atrophy that is characteristic of disease progression. In CTRL-EMCI several brain regions and neuroimaging metrics presented AUC>70% with a worst result in later stages suggesting these indicators as biomarkers for an earlier stage of MCI, although further research is necessary.

A resource for signs and Feynman diagrams of the standart model

When performing a full calculation within the standard model (SM) or its extensions, it is crucial that one utilizes a consistent set of signs for the gauge couplings and gauge fields. Unfortunately, the literature is plagued with differing signs and notations. We present all SM Feynman rules, including ghosts, in a convention-independent notation, and we table the conventions in close to 40 books and reviews.

Could the LHC two-proton signal correspond to the heavier scalar in two-higgs-doublet models?

LHC has reported tantalizing hints for a Higgs boson of mass 125 GeV decaying into two photons. We focus on two-Higgs-doublet Models, and study the interesting possibility that the heavier scalar H has been seen, with the lightest scalar h having thus far escaped detection. Nonobservation of h at LEP severely constrains the parameter-space of two-Higgs-doublet models. We analyze cases where the decay H -> hh is kinematically allowed, and cases where it is not, in the context of type I, type II, lepton-specific, and flipped models.

Metop-A generator for single top production via FCNC interactions

We present a generator for single top-quark production via flavour-changing neutral currents. The MEtop event generator allows for Next-to-Leading-Order direct top production pp -> t and Leading-Order production of several other single top processes. A few packages with definite sets of dimension six operators are available. We discuss how to improve the bounds on the effective operators and how well new physics can be probed with each set of independent dimension six operators.

Theory and phenomenology of two-higgs-doublet models

We discuss theoretical and phenomenological aspects of two-Higgs-doublet extensions of the Standard Model. In general, these extensions have scalar mediated flavour changing neutral currents which are strongly constrained by experiment. Various strategies are discussed to control these flavour changing scalar currents and their phenomenological consequences are analysed. In particular, scenarios with natural flavour conservation are investigated, including the so-called type I and type II models as well as lepton-specific and inert models. Type III models are then discussed, where scalar flavour changing neutral currents are present at tree level, but are suppressed by either a specific ansatz for the Yukawa couplings or by the introduction of family symmetries leading to a natural suppression mechanism. We also consider the phenomenology of charged scalars in these models. Next we turn to the role of symmetries in the scalar sector. We discuss the six symmetry-constrained scalar potentials and their extension into the fermion sector. The vacuum structure of the scalar potential is analysed, including a study of the vacuum stability conditions on the potential and the renormalization-group improvement of these conditions is also presented. The stability of the tree level minimum of the scalar potential in connection with electric charge conservation and its behaviour under CP is analysed. The question of CP violation is addressed in detail, including the cases of explicit CP violation and spontaneous CP violation. We present a detailed study of weak basis invariants which are odd under CP. These invariants allow for the possibility of studying the CP properties of any two-Higgs-doublet model in an arbitrary Higgs basis. A careful study of spontaneous CP violation is presented, including an analysis of the conditions which have to be satisfied in order for a vacuum to violate CP. We present minimal models of CP violation where the vacuum phase is sufficient to generate a complex CKM matrix, which is at present a requirement for any realistic model of spontaneous CP violation.

Marx-Type solid-state bipolar modulator topologies: Performance comparison

The operation of generalized Marx-type solid-state bipolar modulators is discussed and compared with simplified Marx-derived circuits, to evaluate their capability to deal with various load conditions. A comparative analysis on the number of switches per cell, fiber optic trigger count, losses, and switch hold-off voltages has been made. A circuit topology is obtained as a compromise in terms of operating performance, trigger simplicity, and switching losses. A five-stage laboratory prototype of this circuit has been assembled using 1200 V insulated gate bipolar transistors (IGBTs) and diodes, operating with 1000 V dc input voltage and 1 kHz frequency, giving 5 kV bipolar pulses, with 2.5 mu s pulse width and 5 mu s relaxation time into resistive, capacitive, and inductive loads.