Determination of regional flow by use of intravascular PET tracers: Microvascular theory and experimental validation for pig livers

Today, the standard approach for the kinetic analysis of dynamic PET studies is compartment models, in which the tracer and its metabolites are confined to a few well-mixed compartments. We examine whether the standard model is suitable for modern PET data or whether theories including more physiologic realism can advance the interpretation of dynamic PET data. A more detailed microvascular theory is developed for intravascular tracers in single-capillary and multiple-capillary systems. The microvascular models, which account for concentration gradients in capillaries, are validated and compared with the standard model in a pig liver study. Methods: Eight pigs underwent a 5-min dynamic PET study after O-15-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual-inlet concentration was calculated as the flow-weighted inlet concentration. Dynamic PET data were analyzed with a traditional single-compartment model and 2 microvascular models. Results: Microvascular models provided a better fit of the tissue activity of an intravascular tracer than did the compartment model. In particular, the early dynamic phase after a tracer bolus injection was much improved. The regional hepatic blood flow estimates provided by the microvascular models (1.3 +/- 0.3 mL min(-1) mL(-1) for the single-capillary model and 1.14 +/- 0.14 min(-1) mL(-1) for the multiple-capillary model) (mean +/- SEM mL of blood min(-1) mL of liver tissue(-1)) were in agreement with the total blood flow measured by flow meters and normalized to liver weight (1.03 +/- 0.12 mL min(-1) mL(-1)). Conclusion: Compared with the standard compartment model, the 2 microvascular models provide a superior description of tissue activity after an intravascular tracer bolus injection. The microvascular models include only parameters with a clear-cut physiologic interpretation and are applicable to capillary beds in any organ. In this study, the microvascular models were validated for the liver and provided quantitative regional flow estimates in agreement with flow measurements.

Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation

Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [O-15] CO or injections of diffusible 3-O[ C-11] methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time ( T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: (T) over bar = 0.35 +/- 0.05 min for CO and 1.7 +/- 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans.

Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype

Multiple HLA class I alleles can bind peptides with common sequence motifs due to structural similarities in the peptide binding cleft, and these groups of alleles have been classified into supertypes. Nine major HLA supertypes have been proposed, including an A24 supertype that includes A*2301, A*2402, and A*3001. Evidence for this A24 supertype is limited to HLA sequence homology and/or similarity in peptide binding motifs for the alleles. To investigate the immunological relevance of this proposed supertype, we have examined two viral epitopes (from EBV and CMV) initially defined as HLA-A*2301-binding peptides. The data clearly demonstrate that each peptide could be recognized by CTL clones in the context of A*2301 or A*2402; thus validating the inclusion of these three alleles within an A24 supertype. Furthermore, CTL responses to the EBV epitope were detectable in both A*2301(+) and A*2402(+) individuals who had been previously exposed to this virus. These data substantiate the biological relevance of the A24 supertype, and the identification of viral epitopes with the capacity to bind promiscuously across this supertype could aid efforts to develop CTL-based vaccines or immunotherapy. The degeneracy in HLA restriction displayed by some T cells in this study also suggests that the dogma of self-MHC restriction needs some refinement to accommodate foreign peptide recognition in the context of multiple supertype alleles.

Quality of life assessment in the community-dwelling elderly: Validation of the Assessment of Quality of Life (AQoL) Instrument and comparison with the SF-36

Measurement of Health-Related Quality of Life (HRQoL) of the elderly requires instruments with demonstrated sensitivity, reliability, and validity, particularly with the increasing proportion of older people entering the health care system. This article reports the psychometric properties of the 12-item Assessment of Quality of Life (AQoL) instrument in chronically ill community-dwelling elderly people with an 18-month follow-up. Comparator instruments included the SF-36 and the OARS. Construct validity of the AQoL was strong when examined via factor analysis and convergent and divergent validity against other scales. Receiver Operator Characteristic (ROC) curve analyses and relative efficiency estimates indicated the AQoL is sensitive, responsive, and had the strongest predicative validity for nursing home entry. It was also sensitive to economic prediction over the follow-up. Given these robust psychometric properties and the brevity of the scale, AQoL appears to be a suitable instrument for epidemiologic studies where HRQoL and utility data are required from elderly populations. (C) 2003 Elsevier Science Inc. All rights reserved.

Balancing the number and size of sites: An economic approach to the optimal design of cluster samples

The design of randomized controlled trials entails decisions that have economic as well as statistical implications. In particular, the choice of an individual or cluster randomization design may affect the cost of achieving the desired level of power, other things being equal. Furthermore, if cluster randomization is chosen, the researcher must decide how to balance the number of clusters, or sites, and the size of each site. This article investigates these interrelated statistical and economic issues. Its principal purpose is to elucidate the statistical and economic trade-offs to assist researchers to employ randomized controlled trials that have desired economic, as well as statistical, properties. (C) 2003 Elsevier Inc. All rights reserved.

Modified logit life table system: Principles, empirical validation, and application

Despite its widespread use, the Coale-Demeny model life table system does not capture the extensive variation in age-specific mortality patterns observed in contemporary populations, particularly those of the countries of Eastern Europe and populations affected by HIV/AIDS. Although relational mortality models, such as the Brass logit system, can identify these variations, these models show systematic bias in their predictive ability as mortality levels depart from the standard. We propose a modification of the two-parameter Brass relational model. The modified model incorporates two additional age-specific correction factors (gamma(x), and theta(x)) based on mortality levels among children and adults, relative to the standard. Tests of predictive validity show deviations in age-specific mortality rates predicted by the proposed system to be 30-50 per cent lower than those predicted by the Coale-Demeny system and 15-40 per cent lower than those predicted using the original Brass system. The modified logit system is a two-parameter system, parameterized using values of l(5) and l(60).

MOND virial theorem applied to a galaxy cluster

Large values for the mass-to-light ratio (ϒ) in self-gravitating systems is one of the most important evidences of dark matter. We propose a expression for the mass-to-light ratio in spherical systems using MOND. Results for the COMA cluster reveal that a modification of the gravity, as proposed by MOND, can reduce significantly this value.

Residents’ perceptions of tourism impacts in Guimarães (Portugal): a cluster analysis

In this investigation, a cluster analysis was used to separate Guimara˜es (Portugal) residents into clusters according to their perceptions of the impacts of tourism development. This approach is uncommonly applied to Portugal data and is even rarer for world heritage sites. The world heritage designation is believed to make an area more attractive to tourists. The clustering procedure analysed 400 data observations from a Guimara˜es resident survey and revealed the existence of three clusters: the Sceptics, the Moderately Optimistic and the Enthusiasts. The results were consistent with the empirical literature’s results, with the emergent nature of the destination found to be relevant. The fact that tourism is relatively recent in this destination has its major reflex in the devaluation by most of the residents of the negative impacts of tourism development.

Guimarães residents’ perceptions towards tourism impacts: a cluster analysis

The present study was designed to assess and segment local residents with respect to their perceived impacts of Guimarães tourism development. The residents of this municipality (located in the northern part of Portugal) are quite strong in their support to tourism. However, they do not keep a homogeneous perception of tourism impacts. A clusters analysis using data from a survey of 400 Guimarães residents’ has revealed the existence of three clusters, according the different degrees of perceived tourism impacts: the Skeptics - moderate in relation to the benefits (averages range from 2.89-3.74) and the ones more concerned with its costs (averages range from 2.86-3.74); the Moderately optimistic - very optimistic about the benefits of tourism (averages range from 3.74-4.51) and conscious of the costs (averages range from 2.71-3.49); the Enthusiasts - very optimistic about tourism benefits (averages range from 2.92-4.52) and little worried about its costs (averages range from 1.78-3.26). Following the data from the survey, the findings are discussed and a few conclusions are extracted.

Validation of percutaneous puncture trajectory during renal access using 4D ultrasound reconstruction

Background: An accurate percutaneous puncture is essential for disintegration and removal of renal stones. Although this procedure has proven to be safe, some organs surrounding the renal target might be accidentally perforated. This work describes a new intraoperative framework where tracked surgical tools are superimposed within 4D ultrasound imaging for security assessment of the percutaneous puncture trajectory (PPT). Methods: A PPT is first generated from the skin puncture site towards an anatomical target, using the information retrieved by electromagnetic motion tracking sensors coupled to surgical tools. Then, 2D ultrasound images acquired with a tracked probe are used to reconstruct a 4D ultrasound around the PPT under GPU processing. Volume hole-filling was performed in different processing time intervals by a tri-linear interpolation method. At spaced time intervals, the volume of the anatomical structures was segmented to ascertain if any vital structure is in between PPT and might compromise the surgical success. To enhance the volume visualization of the reconstructed structures, different render transfer functions were used. Results: Real-time US volume reconstruction and rendering with more than 25 frames/s was only possible when rendering only three orthogonal slice views. When using the whole reconstructed volume one achieved 8-15 frames/s. 3 frames/s were reached when one introduce the segmentation and detection if some structure intersected the PPT. Conclusions: The proposed framework creates a virtual and intuitive platform that can be used to identify and validate a PPT to safely and accurately perform the puncture in percutaneous nephrolithotomy.

Multi-centre validation of an automatic algorithm for fast 4D myocardial segmentation in cine CMR datasets

Quantitative analysis of cine cardiac magnetic resonance (CMR) images for the assessment of global left ventricular morphology and function remains a routine task in clinical cardiology practice. To date, this process requires user interaction and therefore prolongs the examination (i.e. cost) and introduces observer variability. In this study, we sought to validate the feasibility, accuracy, and time efficiency of a novel framework for automatic quantification of left ventricular global function in a clinical setting.

Paradoxo de inovação no cluster do vinho: o caso da região demarcada do Douro

Este artigo tem por principal objetivo analisar a problemática da inovação no âmbito do cluster de uma região vitivinícola europeia tradicional (Região Demarcada do Douro - Portugal), caracterizada pelo chamado modelo vitivinícola do terroir, uma estrutura econômica suportada por um elevado número de viticultores, pequenas e médias empresas vinícolas e elevada regulação ao longo de toda a cadeia produtiva, em que, claramente, emerge a questão da tradição versus inovação. A pesquisa utilizou o método Grounded Theory, e os resultados evidenciam uma concordância de as empresas permanecerem numa região tradicional, cuja legislação dificulta as inovações radicais, mas que, concomitantemente, assegura os valores da qualidade. Verifica-se uma transferência de valores tradicionais de um produto específico, o vinho do Porto, para os novos produtos lançados recentemente no mercado; e, simultaneamente, uma transferência do valor agregado do vinho do Porto para o valor do vínculo da família com o processo produtivo e com as terras da Região Demarcada do Douro.