Image Registration Measures and Chronic Osteoarthritis Knee Pain Prediction: Data from the Osteoarthritis Initiative / Métricas de Registro de Imágenes y Predicción de Dolor de Rodilla por Osteoartritis Crónica: Datos de la Osteoarthritis Initiative

Abstract Osteoarthritis (OA) is the most common type of arthritis, is a growing disease in the industrialized world. OA is an incapacitate disease that affects more than 1 in 10 adults over 60 years old. X-ray medical imaging is a primary diagnose technique used on staging OA that the expert reads and quantify the stage of the disease. Some Computer-Aided Diagnosis (CADx) efforts to automate the OA detection have been made to aid the radiologist in the detection and control, nevertheless, the pain inherits to the disease progression is left behind. In this research, it's proposed a CADx system that quantify the bilateral similarity of the patient's knees to correlate the degree of asymmetry with the pain development. Firstly, the knee images were aligned using a B-spline image registration algorithm, then, a set of similarity measures were quantified, lastly, using this measures it's proposed a multivariate model to predict the pain development up to 48 months. The methodology was validated on a cohort of 131 patients from the Osteoarthritis Initiative (OAI) database. Results suggest that mutual information can be associated with K&L OAI scores, and Multivariate models predicted knee chronic pain with: AUC 0.756, 0.704, 0.713 at baseline, one year, and two years' follow-up.

Resumen La osteoartritis (OA) es el tipo de artritis más común. OA es una enfermedad limitante que afecta a 1 de 10 adultos con 60 años o más. Las imágenes de rayos-x son una técnica de diagnóstico primario que permite conocer el estado de OA, las cuales el experto lee y cuantifica así la etapa de la enfermedad. El Diagnóstico Asistido por Computadora (CADx, por sus siglas en inglés) ha buscado automatizar el diagnóstico de OA para ayudar al radiólogo en la detección y control; sin embargo, el dolor provocado por la progresión de la enfermedad es dejado atrás. En este trabajo se propone un sistema de CADx que cuantifica la similitud bilateral de las rodillas de los pacientes, con el fin de correlacionar el grado de asimetría con el dolor. Inicialmente, las imágenes de las rodillas fueron alineadas usando el algoritmo B-spline para su registro, después, un conjunto de métricas estándar fue cuantificado; finalmente, con estas métricas se propone un modelo multivariado para predecir el dolor de rodilla desarrollado en 48 meses. La metodología fue validada con 131 pacientes obtenidos de la base de datos de la Osteoarthritis Initiative (OAI). Los resultados sugieren que las métricas pueden ser asociadas con los puntajes de KellgrenLawrence; además, los modelos predicen significativamente el dolor crónico de rodilla con: AUC 0.756, 0.704 y 0.7113, al inicio, un año y dos años después, respectivamente.

General Linear Models for Pain Prediction in Knee Osteoarthritis: Data from the Osteoarthritis Initiative / Modelos Lineales Generales para Predecir Dolor en Osteoartritis de Rodilla: Datos de la "Osteoarthritis Initiative"

Abstract: Knee pain is the most common and disabling symptom in Osteoarthritis (OA). Joint pain is a late manifestation of the OA. In earlier stages of the disease changes in joint structures are shown. Also, formation of bony osteophytes, cartilage degradation, and joint space reduction which are some of the most common, among others. The main goal of this study is to associate radiological features with the joint pain symptom. Univariate and multivariate studies were performed using Bioinformatics tools to determine the relationship of future pain with early radiological evidence of the disease. All data was retrieved from the Osteoarthritis Initiative repository (OAI). A case-control study was done using available data from participants in OAI database. Radiological data was assessed with different OAI radiology groups. We have used quantitative and semi-quantitative scores to measure two different relations between radiological data in three different time points. The goal was to track the appearance and prevalence of pain as a symptom. All predictive models were statistically significant (P ≤ 0,05), obtaining the receiving operating characteristic (ROC) curves with their respective area under the curves (AUC) of 0.6516, 0.6174, and 0.6737 for T-0, T-1 and T-2 in quantitative analysis. For semi-quantitative an AU C of 0.6865, 0.6486, and 0.6406 for T-0, T-1 and T-2. The models obtained in the Bioinformatics study suggest that early joint structure changes can be associated with future joint pain. An image-based biomarker that could predict future pain, measured in early OA stages, could become a useful tool to improve the quality of life of people dealing OA.

Resumen: El dolor de rodilla es el síntoma más común y limitante de la Osteoartritis (OA), además de presentarse como una manifestación tardía de la enfermedad. Los cambios que ocurren en las estructuras de las articulaciones se presentan en las primeras etapas de la OA. Algunos de los cambios más comunes son la formación de osteofitos óseos, degradación del cartílago, y la reducción del espacio en la articulación, entre otros. El principal objetivo de este estudio es la asociación de características radiológicas con el síntoma de dolor de las articulaciones, para lo que fueron realizados dos estudios: univariado y multivariado, usando herramientas bioinformáticas para determinar la relación de futuro dolor con la evidencia radiológica temprana de la enfermedad. Todos los datos fueron recuperados de la Osteoarthritis Initiative repository (OAI). Este estudio de caso-control se llevó a cabo utilizando los datos disponibles de los participantes de la base de datos de la OAI. Los datos radiológicos fueron evaluados con diferentes grupos de radiología de la OAI. Fueron usadas puntuaciones cuantitativas y semi- cuantitativas para medir las dos diferentes relaciones entre los datos radiológicos en tres diferentes puntos de tiempo. El objetivo fue seguir la trayectoria de la aparición y prevalencia del dolor como síntoma. Todos los modelos predictivos fueron estadísticamente significativos (P ≤ 0,05). Para el análisis cuantitativo se calcularon las áreas bajo la curva (AUC): 0.6516, 0.6174, y 0.6737 para T-0, T-1 y T-2, y para el análisis semi-cuantitativo se calcularon las AU C: 0.6865, 0.6486, y 0.6406 para T-0, T-1 y T-2. Los modelos obtenidos en el estudio bioinformático sugieren que los cambios tempranos en la estructura de las articulaciones pueden estar asociados con el futuro dolor de rodilla. Un biomarcador basado en imágenes que pueda predecir el futuro dolor, medido en las primeras etapas de OA, podría convertirse en una herramienta útil para mejorar la calidad de vida de la gente que padece OA.

Current model systems for the study of preeclampsia.

Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal-fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein-protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.

Temporal phase-unwrapping of static surfaces with 2-sensitivity fringe-patterns.

Here we describe a 2-step temporal phase unwrapping formula that uses 2-sensitivity demodulated phases for measuring static surfaces. The first phase demodulation has at most 1-wavelength sensitivity and the second one is G-times (G>>1.0) more sensitive. Measuring static surfaces with 2-sensitivity fringe patterns is well known and recent published methods combine 2-sensitivities measurements mostly by triangulation. Two important applications for our 2-step unwrapping algorithm is profilometry and synthetic aperture radar (SAR) interferometry. In these two applications the object or surface being analyzed is static and highly discontinuous; so temporal unwrapping is the best strategy to follow. Phase-demodulation in profilometry and SAR interferometry is very similar because both share similar mathematical models.

High-resolution low-noise 360-degree digital solid reconstruction using phase-stepping profilometry.

In this paper we describe a high-resolution, low-noise phase-shifting algorithm applied to 360 degree digitizing of solids with diffuse light scattering surface. A 360 degree profilometer needs to rotate the object a full revolution to digitize a three-dimensional (3D) solid. Although 360 degree profilometry is not new, we are proposing however a new experimental set-up which permits full phase-bandwidth phase-measuring algorithms. The first advantage of our solid profilometer is: it uses base-band, phase-stepping algorithms providing full data phase-bandwidth. This contrasts with band-pass, spatial-carrier Fourier profilometry which typically uses 1/3 of the fringe data-bandwidth. In addition phase-measuring is generally more accurate than single line-projection, non-coherent, intensity-based line detection algorithms. Second advantage: new fringe-projection set-up which avoids self-occluding fringe-shadows for convex solids. Previous 360 degree fringe-projection profilometers generate self-occluding shadows because of the elevation illumination angles. Third advantage: trivial line-by-line fringe-data assembling based on a single cylindrical coordinate system shared by all 360-degree perspectives. This contrasts with multi-view overlapping fringe-projection systems which use iterative closest point (ICP) algorithms to fusion the 3D-data cloud within a single coordinate system (e.g. Geomagic). Finally we used a 400 steps/rotation turntable, and a 640x480 pixels CCD camera. Higher 3D digitized surface resolutions and less-noisy phase measurements are trivial by increasing the angular-spatial resolution and phase-steps number without any substantial change on our 360 degree profilometer.

Synchronous phase-demodulation and harmonic rejection of 9-step pixelated dynamic interferograms.

We propose a novel synchronous phase-demodulation of pixelated interferograms using squared 3x3 phase-shifted unit-cells. This 3x3 unit-cell is tiled over the CCD image sensor to create a two-dimensional (2D) pixelated carrier. Our synchronous phase-demodulation uses this 2D carrier to demodulate the pixelated interferogram as in the standard 2x2 unit-cell case. The main motivation behind the use of a 3x3 pixelated carrier (instead of the usual 2x2) is its higher harmonic robustness, allowing one to demodulate intensity-distorted fringe patterns. The harmonic rejection robustness of our spatial 3x3 configuration equals the robustness of the temporal least-squares 9-step phase-shifting algorithm (PSA). In other words, extending from the usual 2x2 phase-shifting unit-cell to 3x3 unit-cells, one extends the harmonic rejection of the demodulation algorithm. Finally we also prove that our proposed 9-step, 3x3 pixelated carrier uses the 2D available spectral space more efficiently than using these 9-steps in a linear spatial-carrier configuration.

Harmonics rejection in pixelated interferograms using spatio-temporal demodulation.

Pixelated phase-mask interferograms have become an industry standard in spatial phase-shifting interferometry. These pixelated interferograms allow full wavefront encoding using a single interferogram. This allows the study of fast dynamic events in hostile mechanical environments. Recently an error-free demodulation method for ideal pixelated interferograms was proposed. However, non-ideal conditions in interferometry may arise due to non-linear response of the CCD camera, multiple light paths in the interferometer, etc. These conditions generate non-sinusoidal fringes containing harmonics which degrade the phase estimation. Here we show that two-dimensional Fourier demodulation of pixelated interferograms rejects most harmonics except the complex ones at {-3(rd), +5(th), -7(th), +9(th), -11(th),…}. We propose temporal phase-shifting to remove these remaining harmonics. In particular, a 2-step phase-shifting algorithm is used to eliminate the -3(rd) and +5(th) complex harmonics, while a 3-step one is used to remove the -3(rd), +5<(th), -7(th) and +9(th) complex harmonics.

Co-ordination between leaf initiation and leaf appearance in field-grown maize (Zea mays): genotypic differences in response of rates to temperature.

BACKGROUND AND AIMS: In maize (Zea mays), early flowering date, which is a valuable trait for several cropping systems, is associated with the number of leaves per plant and the leaf appearance rate. Final leaf number depends upon the rate and duration of leaf initiation. The aims of this study were to analyse the genotypic variation in the response to temperature of leaf appearance rate and leaf initiation rate, and to investigate the co-ordination between these processes under field conditions. METHODS: Sixteen hybrids of different origins were grown under six contrasting environmental conditions. The number of appeared leaves was measured twice a week to estimate leaf appearance rate (leaves d(-1)). Plants were dissected at four sampling dates to determine the number of initiated leaves and estimate leaf initiation rate (leaves d(-1)). A co-ordination model was fitted between the number of initiated leaves and the number of appeared leaves. This model was validated using two independent data sets. KEY RESULTS: Significant (P < 0.05) differences were found among hybrids in the response to temperature of leaf initiation rate (plastochron) and leaf appearance rate (phyllochron). Plastochron ranged between 24.3 and 36.4 degree days (degrees Cd), with a base temperature (Tb) between 4.0 and 8.2 degrees C. Phyllochron ranged between 48.6 and 65.5 degrees Cd, with a Tb between 2.9 and 5.0 degrees C. A single co-ordination model was fitted between the two processes for all hybrids and environments (r2= 0.96, P < 0.0001), and was successfully validated (coefficient of variation < 9 %). CONCLUSIONS: This work has established the existence of genotypic variability in leaf initiation rate and leaf appearance rate in response to temperature, which is a promising result for maize breeding; and the interdependence between these processes from seedling emergence up to floral initiation.

[Diffuse primary malignant mesothelioma in abdominal cavity]. / Mesotelioma maligno primário difuso em cavidade abdominal.

Two cases of diffuse malignant mesothelioma of abdominal cavity were analysed. These tumors arise from the peritoneum and are also found in the parietal and visceral pleura, pericardium and in vaginal tunic. All of them, infra or supra-diaphragmatic, are associated with asbestos exposure in at least 80% of cases. It is difficult to explain how inhaled asbestos induces peritoneal neoplasms. This aspects become very important in the diagnostic, basically why it is done at laparotomy or laparoscopy. When was proceed the biopsy of the lesions, and occasionally by identification of malignant mesothelial cells in ascitic fluid. In this two cases exposed considerations about the advanced phase of diagnostic are made, the diagnostic was performed in the majority of the collected cells, showing the advanced stage of the disease. At that time of diagnosis we observed poor evolution. We call attention to the importance of precancer diagnosis, the best chance to treatment options, always based on surgical resections, radiation or chemotherapy alone or combined. If the radical surgery is not possible, this patients must be treated by chemotherapy or radiotherapy, defined after complete staging of the disease.

Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype.

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects.

Familial translocation 5;14 resulting in an unbalanced offspring.

We report on an infant with multiple congenital anomalies possessing a derivative 14 chromosome in excess of the normal complement, resulting from transmission of a familial t(5;14)(p13;q22). The proposita's phenotypically normal mother, mentally retarded half-brother, and fetal sib are carriers of the apparently balanced translocation. Previous cases of similar familial t(5;14) are reviewed. The proposita's phenotype is characterized by failure to thrive, developmental retardation, cleft palate, congenital heart anomaly, abnormal hands and feet, unusual face with abnormal ears, and recurrent respiratory infections. The proposita died at age 9 months and postmortem examination showed multiple central nervous system, cardiopulmonary, gastrointestinal, and genital malformations. Our proposita's phenotype is attributable to contributions from both chromosomes and is consistent with the consequences of both the dup(5p) and dup(14q).

Trisomy 18 and 18p- features in a case of isochromosome 18q [46,XY,i(18q)]: prenatal diagnosis and autopsy report.

This paper reports the prenatal diagnosis and autopsy findings of a case of true isochromosome 18q [46,XY,i(18q)] with severe cephalic malformations. Comparison is made with other cases of i(18q).

Field orientation effects during 5.6-GHz radiofrequency irradiation of rats.

Ketamine-anesthetized Sprague-Dawley rats were exposed in E and H orientations (long axis parallel to electric and magnetic fields, respectively) to far-field 5.6-GHz continuous-wave radio-frequency radiation (RFR). Power densities were used that resulted in equivalent whole-body average specific absorption rates of 14 W/kg in both orientations (90 mW/cm2 for E and 66 mW/cm2 for H). Irradiation was conducted to increase colonic temperature by 1 degree C (from 38.5 to 39.5 degrees C). During experimentation, arterial blood pressure and respiratory rate and colonic, tympanic, left and right subcutaneous (sides toward and away from RFR source), and tail temperatures were continuously recorded. Results showed no significant difference in the times required to cause a 1 degree C increase or to recover to the initial temperature when irradiation was stopped. Significant differences between E- and H-orientation exposure were seen in the patterns of localized heating. The tail and left subcutaneous temperature increases were significantly greater during E-orientation exposure, the tympanic site showed no difference, and the right subcutaneous temperature increase was significantly greater during H-orientation exposure. Under both exposure conditions, heart rate and mean arterial blood pressure significantly increased during irradiation; however, there were no significant differences between E and H orientation responses. These findings at 5.6 GHz are in contrast to the significant cardiovascular response differences between E- and H-orientation exposure noted during a previous study of irradiation at 2.45 GHz.

Thermal and physiologic responses to 1200-MHz radiofrequency radiation: differences between exposure in E and H orientation.

Ketamine-anesthetized Sprague-Dawley rats were exposed to far-field 1200-MHz continuous wave radiofrequency radiation in both E and H orientations (long axis of animal parallel to electric or magnetic field, respectively). Power densities were used that resulted in equivalent whole-body specific absorption rates of approximately 8 W/kg in both orientations (20 mW/cm2 for E and 45 mW/cm2 for H). Exposure was conducted to repeatedly increase colonic temperature from 38.5 to 39.5 degrees C in both orientations in the same animal. Irradiation in E orientation resulted in greater colonic, tympanic, left subcutaneous (side toward antenna), and tail heating. The results indicated a more uniform distribution of heat than that which occurred in previous experiments of 2450-MHz irradiation in E and H orientation. A lack of significant differences in blood pressure and heart rate responses between exposures in the two orientations in this study suggest that greater peripheral heating, as was seen in the earlier study of 2450 MHz, is necessary for these differences to occur.

Objective assessment of topical anti-inflammatory drug activity on experimentally induced nickel contact dermatitis: comparison between visual scoring, colorimetry, laser Doppler velocimetry and transepidermal water loss.

Four topical anti-inflammatory drugs were investigated for their effect on allergic contact dermatitis. Nickel dermatitis was chosen for its high incidence in European healthy volunteers. Experimental lesions were treated twice daily with two steroids, two non-steroidal anti-inflammatory drugs and a blank base for 4.5 days without occlusion. The influence of treatments was assessed by daily visual grading and one site was left untreated for comparison over the same period. To quantify drug activities objectively, skin colour (colorimetry), skin blood flow (laser Doppler velocimetry) and transepidermal water loss (evaporimetry) were measured before drugs were first applied, then 6 hr after the last application. As expected, only Dermoval cream significantly improved the spontaneous clinical evolution in comparison with the other creams (Hydrocortisone Aster à 1%. Parfenac, indomethacin 2.5% and Skinbase) and the untreated site. Colorimetric parameter a* (redness) and L* (luminance) showed more differences between treatments than the other criteria and a close relationship was obtained between these two parameters and skin blood flow, all three being highly correlated to visual grading. Transepidermal water loss appeared less related to clinical improvement but this parameter could prove helpful for detecting compounds which could be irritant to diseased skin.

Thermal and physiological changes in rats exposed to CW and pulsed 2.8 GHz radiofrequency radiation in E and H orientations.

Ketamine-anesthetized Sprague-Dawley rats were exposed in both E and H orientations to far-field 2.8 GHz continuous-wave (CW) and pulsed (0.5 microseconds, 500 pps) radiofrequency radiation (RFR) at equivalent whole-body average specific absorption rates (SAR) of approximately 14 W/kg. Intermittent irradiation was performed in all four exposure conditions, in the same animal, to repeatedly increase colonic temperature from 38.5 to 39.5 degrees C. Tympanic, subcutaneous (sides toward and away from RF sources), colonic, and tail temperatures, electrocardiogram, arterial blood pressure, and respiratory rate were continuously recorded. The results revealed no significant difference between the thermal effects of CW and pulsed RFR exposure. The results did show significant differences between the thermal effects of E- and H-orientation exposure. H-orientation irradiation produced significantly faster colonic temperature increases and, with the exception of the tail, produced significantly greater localized heating in the anesthetized rat, and higher local SAR in rat carcasses than did E-orientation exposure. Under all exposure conditions, heart rate and blood pressure increased significantly during irradiation and returned to baseline when exposure was discontinued. Respiratory rate remained unchanged during irradiation. There were no significant differences between the effects of E- and H-orientation exposure, or between CW and pulsed irradiation, upon heart rate, blood pressure, and respiratory rate.

[Impact of the spraying of deltamethrin in a focus of leishmaniasis in Bolivia]. / Impact de pulvérisations de deltaméthrine dans un foyer de leishmaniose de Bolivie.

After one month of entomological observations to record pretreatment data, a sub Andean village of Yungas, Bolivia (alt. 1500 m) was sprayed at the beginning of the rainy season (January 1987). Houses were treated inside and outside with deltamethrin at 0.025 g/sq.m.; kennels, hen-houses and stacks of adobe were also sprayed in the same way. As a result of the treatment, Lutzomyia longipalpis, the local vector of visceral leishmaniasis, disappeared from houses and animal shelters for 9 and 10 months respectively. The impact of the treatment on the populations of Lu. nuneztovari and anglesi, the presumed vector of tegumentary leishmaniasis, was not obvious. As compared with pretreatment data, the rate of engorged females in houses decreased by two, and their density was also reduced. But these data are difficult to interpret due to the natural seasonal variation in density in this species. Moreover, the information from the control village did not correspond as expected. Lu. n. anglesi is a highly exophilic species in this area, a behaviour which could explain the limited impact of the treatment on this sandfly.

Effects of field orientation during 700-MHz radiofrequency irradiation of rats.

Ketamine-anesthetized Sprague-Dawley rats were exposed to far-field 700-MHz continuous-wave radiofrequency radiation (RFR) in both E and H orientations. Irradiation was conducted at whole-body average specific absorption rates (SARs) of 9.2 and 13.0 W/kg (E and H, respectively) that resulted in approximately equivalent colonic specific heating rates (SHRs). Exposures were performed to repeatedly increase colonic temperature by 1 degree C (38.5 to 39.5 degrees C). Tympanic, tail, left and right subcutaneous (toward and away from RFR source), and colonic temperatures, arterial blood pressure, and respiratory rate were continuously recorded. In spite of equivalent colonic SHRs and the reduced E-orientation average SAR, the right subcutaneous, tympanic, and tail SARs, SHRs and absolute temperature increases were significantly greater in E than in H orientation. The cooling rate at all monitoring sites was also significantly greater in E than in H orientation. Heart rate and mean arterial blood pressure significantly increased during irradiation; however, changes between orientations were not different. Respiratory rate significantly increased during irradiation in H, but not in E orientation. These results indicate that during resonant frequency irradiation, differences occur in the pattern of heat deposition between E- and H-orientation exposure. When compared with previous investigations performed at supraresonant frequencies, the lower level of cardiovascular change in this study was probably related to the lower periphery-to-core thermal gradient.