A Dynamic Model of Hand-and-Foot Syndrome in Patients Receiving Capecitabine

For the purpose of developing a longitudinal model to predict hand-and-foot syndrome (HFS) dynamics in patients receiving capecitabine, data from two large phase III studies were used. Of 595 patients in the capecitabine arms, 400 patients were randomly selected to build the model, and the other 195 were assigned for model validation. A score for risk of developing HFS was modeled using the proportional odds model, a sigmoidal maximum effect model driven by capecitabine accumulation as estimated through a kinetic-pharmacodynamic model and a Markov process. The lower the calculated creatinine clearance value at inclusion, the higher was the risk of HFS. Model validation was performed by visual and statistical predictive checks. The predictive dynamic model of HFS in patients receiving capecitabine allows the prediction of toxicity risk based on cumulative capecitabine dose and previous HFS grade. This dose-toxicity model will be useful in developing Bayesian individual treatment adaptations and may be of use in the clinic.

A two-dimensional fuzzy random model of soil pore structure

A new conceptual model for soil pore-solid structure is formalized. Soil pore-solid structure is proposed to comprise spatially abutting elements each with a value which is its membership to the fuzzy set ''pore,'' termed porosity. These values have a range between zero (all solid) and unity (all pore). Images are used to represent structures in which the elements are pixels and the value of each is a porosity. Two-dimensional random fields are generated by allocating each pixel a porosity by independently sampling a statistical distribution. These random fields are reorganized into other pore-solid structural types by selecting parent points which have a specified local region of influence. Pixels of larger or smaller porosity are aggregated about the parent points and within the region of interest by controlled swapping of pixels in the image. This creates local regions of homogeneity within the random field. This is similar to the process known as simulated annealing. The resulting structures are characterized using one-and two-dimensional variograms and functions describing their connectivity. A variety of examples of structures created by the model is presented and compared. Extension to three dimensions presents no theoretical difficulties and is currently under development.

An isolated perfused human placental lobule model for multiple indicator dilution studies

We describe a method for multiple indicator dilution studies in the isolated perfused human placental lobule developed to investigate the relationships between changes in pressure and flow and solute clearance. A peripheral lobule of a human placenta is perfused with a tissue culture-based medium and the perfusate oxygen tension, arterial and venous pressures, pH and perfusion temperature continuously monitored by a computerized system. Flow rates are readily changed. Bolus injections of vascular, extracellular and water space markers, and study compounds can be made into either maternal or fetal circulations, and precisely timed outflow fractions can be collected with computer-controlled fraction collectors, allowing simultaneous determination of concentration-time profiles of each marker. (C) 1997 Elsevier Science Inc.

Exploring the knowledge contained in neuroimages: Statistical discriminant analysis and automatic segmentation of the most significant changes

Objective: The aim of this article is to propose an integrated framework for extracting and describing patterns of disorders from medical images using a combination of linear discriminant analysis and active contour models. Methods: A multivariate statistical methodology was first used to identify the most discriminating hyperplane separating two groups of images (from healthy controls and patients with schizophrenia) contained in the input data. After this, the present work makes explicit the differences found by the multivariate statistical method by subtracting the discriminant models of controls and patients, weighted by the pooled variance between the two groups. A variational level-set technique was used to segment clusters of these differences. We obtain a label of each anatomical change using the Talairach atlas. Results: In this work all the data was analysed simultaneously rather than assuming a priori regions of interest. As a consequence of this, by using active contour models, we were able to obtain regions of interest that were emergent from the data. The results were evaluated using, as gold standard, well-known facts about the neuroanatomical changes related to schizophrenia. Most of the items in the gold standard was covered in our result set. Conclusions: We argue that such investigation provides a suitable framework for characterising the high complexity of magnetic resonance images in schizophrenia as the results obtained indicate a high sensitivity rate with respect to the gold standard. (C) 2010 Elsevier B.V. All rights reserved.

Endoscopic Anatomy of the Pterygopalatine Fossa and the Transpterygoid Approach: Development of a Surgical Instruction Model

Introduction: The pterygopalatine fossa (PPF) is a narrow space located between the posterior wall of the antrum and the pterygoid plates. Surgical access to the PPF is difficult because of its protected position and its complex neurovascular anatomy. Endonasal approaches using rod lens endoscopes, however, provide better visualization of this area and are associated with less morbidity than external approaches. Our aim was to develop a simple anatomical model using cadaveric specimens injected with intravascular colored silicone to demonstrate the endoscopic anatomy of the PPF. This model could be used for surgical instruction of the transpterygoid approach. Methods: We dissected six PPF in three cadaveric specimens prepared with intravascular injection of colored material using two different injection techniques. An endoscopic endonasal approach, including a wide nasoantral window and removal of the posterior antrum wall, provided access to the PPF. Results: We produced our best anatomical model injecting colored silicone via the common carotid artery. We found that, using an endoscopic approach, a retrograde dissection of the sphenopalatine artery helped to identify the internal maxillary artery (IMA) and its branches. Neural structures were identified deeper to the vascular elements. Notable anatomical landmarks for the endoscopic surgeon are the vidian nerve and its canal that leads to the petrous portion of the internal carotid artery (ICA), and the foramen rotundum, and V2 that leads to Meckel`s cave in the middle cranial fossa. These two nerves, vidian and V2, are separated by a pyramidal shaped bone and its apex marks the ICA. Conclusion: Our anatomical model provides the means to learn the endoscopic anatomy of the PPF and may be used for the simulation of surgical techniques. An endoscopic endonasal approach provides adequate exposure to all anatomical structures within the PPF. These structures may be used as landmarks to identify and control deeper neurovascular structures. The significance is that an anatomical model facilitates learning the surgical anatomy and the acquisition of surgical skills. A dissection superficial to the vascular structures preserves the neural elements. These nerves and their bony foramina, such as the vidian nerve and V2, are critical anatomical landmarks to identify and control the ICA at the skull base.

PHOTOELASTIC ANALISYS OF A HUMAN VERTEBRA MODEL WITH PEDICULAR SCREW

Introduction: The vertebrae fixation system using pedicular screws is one of the most efficient methods to treat vertebral spine pathologies. When the screw is submitted to pullout strength, it causes internal tension near the medullar canal and this situation can be analyzed by using the photoelasticity technique. Objective: Were analyzed those internal tensions near the medullar canal of photoelastic vertebra models using different sizes of screws of the vertebral fixation system submitted to pullout strength. Methods: A lumbar vertebral model made of photoelastic material with three different USS1-type pedicular screw sizes (5, 6, and 7 mm) was used. The internal tensions around the screw were tested in 12 predetermined points by a plain transmission polaroscope. Results: The areas of greater tension concentration were between the medullar canal and the curves of the transverse process. Comparing the maximum average pulling tension, statistical differences were observed between screws 5 and 7, and 6 and 7. On the other hand, for screws 5 and 6, there were no significant differences. Conclusion: The study evidenced that the internal tensions are greater in irregular areas, next to the medullar canal, showing that this is a critical region.

Tension band wire fixation for valgus osteotomies of the proximal femur: A biomechanical study of three configurations of fixation

Background. A variety of techniques can be used to achieve stabilization of femoral valgus osteotomies in children, but what is lacking is a versatile fixation system that associates stability and versatility at different ages and for different degrees of deformity. Methods. Mechanical tests of three configurations used to fix femoral valgus osteotomies, based oil the tension band wire principle, were carried out. A 30 degrees wedge valgus osteotomy was performed at the subtrochanteric level in 60 swine femurs and fixed with three different systems. In Group 1, two Kirschner wires (K wire) were introduced from the tip of the greater trochanter to the medial cortex, crossing the osteotomy. A flexible steel wire was anchored to the K wires into holes in the lateral cortex and tightened to form a tension band. The same setup was used in Group 2, but two additional smooth K wires were inserted into the lateral surface of the greater trochanter and driven to the femoral head with the distal extremities bent and tied around tile bone shaft. In Group 3, the fixation was similar to that in Group 2, but tile ascending K wires were introduced below the osteotomy level, crossing the osteotonly. Mechanical tests in bending-compression and torsion were used to access the stability. Findings. The torsional relative stiffness was 116% greater for Group 3 (0.27 N m/degree) and no significant difference was found between Group 1 (0.10 N m/degree) and Group 2 (0.12 N m/degree). The average torque was 103% higher for Group 3 (1.86 N m). Stiffness in bending-compression was significantly higher in Group 3 (508 x 10(3) N/m) than in Group 1 (211 x 10(3) N/m) and Group 2 (219 x 10(3) N/m). Interpretation. Fixation as used in Group 3 was significantly more stable, both in torsion and bending-compression tests, than tile other two techniques. (c) 2007 Elsevier Ltd. All rights reserved.

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23 +/- 0.1 vs. 1.32 +/- 0.2 ms(2)) and HF (6.6 +/- 0.49 vs. 15.1 +/- 0.61 ms(2)) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3 +/- 2.7 vs. 7.4 +/- 1.01 mmHg(2)) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (- 1.83 +/- 0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23 +/- 0.06 bpm/MmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels. (c) 2008 Elsevier B.V. All rights reserved.

Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings

High-level microsatellite instability (AISI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting In the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might he discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of bMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant beta -catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation, which were infrequent in both groups. Sporadic MSI-H cancers were more frequently heterogeneous (P < 0.001), poorly differentiated (P = 0.02), mucinous (P = 0.02), and proximally located (P = 0.04) than RNPCC tumors. In sporadic MSI-H cancers, contiguous adenomas were likely to be serrated whereas traditional adenomas were dominant in HNPCC. Lymphocytic infiltration was more pronounced in HNPCC but the results did not reach statistical significance. Overall, HNPCC cancers were more like common colorectal cancer in terms of morphology and expression of beta -catenin whereas sporadic MSI-H cancers displayed features consistent with a different morphogenesis. No individual feature was discriminatory for all RN-PCC cancers. However, a model based on four features was able to classify 94.5% of tumors as sporadic or HNPCC. The finding of multiple differences between sporadic and familial MSI-H colorectal cancer with respect to both genotype and phenotype is consistent with tumorigenesis through parallel evolutionary pathways and emphasizes the importance of studying the two groups separately.

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Simulation of the load-unload response ratio and critical sensitivity in the lattice solid model

The Load-Unload Response Ratio (LURR) method is an intermediate-term earthquake prediction approach that has shown considerable promise. It involves calculating the ratio of a specified energy release measure during loading and unloading where loading and unloading periods are determined from the earth tide induced perturbations in the Coulomb Failure Stress on optimally oriented faults. In the lead-up to large earthquakes, high LURR values are frequently observed a few months or years prior to the event. These signals may have a similar origin to the observed accelerating seismic moment release (AMR) prior to many large earthquakes or may be due to critical sensitivity of the crust when a large earthquake is imminent. As a first step towards studying the underlying physical mechanism for the LURR observations, numerical studies are conducted using the particle based lattice solid model (LSM) to determine whether LURR observations can be reproduced. The model is initialized as a heterogeneous 2-D block made up of random-sized particles bonded by elastic-brittle links. The system is subjected to uniaxial compression from rigid driving plates on the upper and lower edges of the model. Experiments are conducted using both strain and stress control to load the plates. A sinusoidal stress perturbation is added to the gradual compressional loading to simulate loading and unloading cycles and LURR is calculated. The results reproduce signals similar to those observed in earthquake prediction practice with a high LURR value followed by a sudden drop prior to macroscopic failure of the sample. The results suggest that LURR provides a good predictor for catastrophic failure in elastic-brittle systems and motivate further research to study the underlying physical mechanisms and statistical properties of high LURR values. The results provide encouragement for earthquake prediction research and the use of advanced simulation models to probe the physics of earthquakes.

Bridging the gap between different statistical approaches: An integrated framework for modelling

This paper proposes a template for modelling complex datasets that integrates traditional statistical modelling approaches with more recent advances in statistics and modelling through an exploratory framework. Our approach builds on the well-known and long standing traditional idea of 'good practice in statistics' by establishing a comprehensive framework for modelling that focuses on exploration, prediction, interpretation and reliability assessment, a relatively new idea that allows individual assessment of predictions. The integrated framework we present comprises two stages. The first involves the use of exploratory methods to help visually understand the data and identify a parsimonious set of explanatory variables. The second encompasses a two step modelling process, where the use of non-parametric methods such as decision trees and generalized additive models are promoted to identify important variables and their modelling relationship with the response before a final predictive model is considered. We focus on fitting the predictive model using parametric, non-parametric and Bayesian approaches. This paper is motivated by a medical problem where interest focuses on developing a risk stratification system for morbidity of 1,710 cardiac patients given a suite of demographic, clinical and preoperative variables. Although the methods we use are applied specifically to this case study, these methods can be applied across any field, irrespective of the type of response.

Travel preferences of the residents of Guimarães: a revised model of push and pull motives

The historic center of the Portuguese city of Guimarães is a world heritage site (UNESCO) since 2001, having hosted the European Capital of Culture (ECOC) in 2012. In this sense, Guimarães has made a major effort in promoting tourism, positioning itself as an urban and cultural tourism destination. The present paper has two objectives. The first, to examine if an existing push and pull motivation model finds statistical support with regard to the population of the municipality of Guimarães, a cultural tourism destination. The second, to study the role that important socio-demographic variables, such as gender, age, and education, play in determining travel motivations of residents from this municipality. Insight on tourism motivation may be an important policy tool for tourism planners and managers in the development of products and marketing strategies. The empirical analysis is undertaken based on questionnaires administered in 2012 to residents of Guimarães. The present study shows that gender, age and education make a difference with regard to travel motivations.

A model for the evaluation of data quality in health unit website

This article presents a research work, the goal of which was to achieve a model for the evaluation of data quality in institutional websites of health units in a broad and balanced way. We have carried out a literature review of the available approaches for the evaluation of website content quality, in order to identify the most recurrent dimensions and the attributes, and we have also carried out a Delphi method process with experts in order to reach an adequate set of attributes and their respective weights for the measurement of content quality. The results obtained revealed a high level of consensus among the experts who participated in the Delphi process. On the other hand, the different statistical analysis and techniques implemented are robust and attach confidence to our results and consequent model obtained.

A 3-phase model for VIS/NIR mu C-Si : H p-i-n detectors

The spectral response and the photocurrent delivered by entirely microcrystalline p-i-n-Si:H detectors an analysed under different applied bias and light illumination conditions. The spectral response and the internal collection depend not only on the energy range but also on the illumination side. Under [p]- and [n]-side irradiation, the internal collection characteristics have an atypical shape. It is high for applied bias and lower than the open circuit voltage, shows a steep decrease near the open circuit voltage (higher under [n]-side illumination) and levels off for higher voltages. Additionally, the numerical modeling of the VIS/NIR detector, based on the band discontinuities near the grain boundaries and interfaces, complements the study and gives insight into the internal physical process.