Spinal Cord Diffusion-Tensor Imaging and Motor-evoked Potentials in Multiple Sclerosis Patients: Microstructural and Functional Asymmetry

Purpose: To assess possible association between intrinsic structural damage and clinical disability by correlating spinal cord diffusion-tensor (DT) imaging data with electrophysiological parameters in patients with a diagnosis of multiple sclerosis (MS). Materials and Methods: This study was approved by the local ethical committee according to the declaration of Helsinki and written informed consent was obtained. DT images and T1- and T2-weighted images of the spinal cord were acquired in 28 healthy volunteers and 41 MS patients. Fractional anisotropy (FA) and apparent diffusion coefficients were evaluated in normal-appearing white matter (NAWM) at the cervical level and were correlated with motor-evoked potentials (n = 34). Asymmetry index was calculated for FA values with corresponding left and right regions of interest as percentage of the absolute difference between these values relative to the sum of the respective FA values. Statistical analysis included Spearman rank correlations, Mann-Whitney test, and reliability analysis. Results: Healthy volunteers had low asymmetry index (1.5%-2.2%). In MS patients, structural abnormalities were reflected by asymmetric decrease of FA (asymmetry index: 3.6%; P = .15). Frequently asymmetrically affected among MS patients was left and right central motor conduction time (CMCT) to abductor digiti minimi muscle (ADMM) (asymmetry index, 15%-16%) and tibialis anterior muscle (TAM) (asymmetry index, 9.5%-14.1%). Statistically significant correlations of functional (ie, electrophysiological) and structural (ie, DT imaging) asymmetries were found (P = .005 for CMCT to ADMM; P = .007 for CMCT to TAM) for the cervical lateral funiculi, which comprise the crossed pyramidal tract. Interobserver reliability for DT imaging measurements was excellent (78%-87%). Conclusion: DT imaging revealed asymmetric anatomic changes in spinal cord NAWM, which corresponded to asymmetric electrophysiological deficits for both arms and legs, and reflected a specific structure-function relationship in the human spinal cord. © RSNA, 2013.

The value of conservative treatment in ruptures of the anterior cruciate ligament (ACL)

BACKGROUND: Thirty-eight of the 73 consecutive acute ruptures of the anterior cruciate ligament (ACL) proven by a magnetic resonance imaging scan (MRI) in skeletally mature patients (16-55 years old) were classified as suitable for primarily conservative treatment. Patient selection was performed using a preoperative screening protocol based on the structural damage, clinical symptoms, compliance, sportive activity, and the consent of a well-informed patient. METHODS: In 12 of the 38 treated patients, the conservative protocol showed a good to very good outcome, 2 patients had persistent giving-way and were considering ACL reconstruction, 14 patients had a secondary ACL reconstruction in our clinic (average 5.3 months after injury), 9 patients were operated on in other hospitals (average 13.3 months after injury), and 1 patient was lost to follow-up. RESULTS: All patients with successful conservative treatment were able to perform low-risk pivoting sports and two patients are practicing high-risk pivoting sports. The average International Knee Documentation Committee (IKDC) score was 92.5 (82.8-98.9); the subjective overall knee function was 93% (60% to 100%). Of the 12 patients with good and very good results, 6 continued playing the same sports at an unreduced intensity, 4 patients reduced their activities slightly, and 1 patient played more sports than before. CONCLUSIONS: Although the authors performed a preoperative screening to select patients suitable for conservative treatment, almost two-thirds of the primarily conservatively treated ACL ruptures needed an operative reconstruction in the long term. In one-third of the patients, conservative treatment led to a good or very good result. At the endpoint of the study only 12 (16%) of a total of 73 patients with acute injuries of the ACL had successful conservative treatment. Therefore, patients must be comprehensively instructed about the treatment program and the chances of success of conservative ACL treatment.

The role of the sinuses of Valsalva in aortic root flow dynamics and aortic root surgery: evaluation by magnetic resonance imaging

BACKGROUND AND AIM OF THE STUDY: Combined replacement of the aortic valve and ascending aorta using a composite graft represents the standard treatment for dilated aortic root with concomitant structural damage of the aortic valve, especially when the aortic valve cannot be preserved. Unfortunately, hemodynamic changes associated with prosthetic replacement of the aortic root have not been fully elucidated. The study aim was to compare hemodynamics within the replaced aortic root using either a prosthetic vascular graft with bulges mimicking the sinuses of Valsalva and including a stented pericardial valve, or a straight xenopericardial conduit and a stentless porcine valve. METHODS: Between July 2004 and March 2006, a total of 35 patients (mean age 65.2 years: range: 32-80 years) was enrolled into the present study. Aortic root replacement was performed in nine patients with a Valsalva graft (Gelweave Valsalva; Vascutek, Renfrewshire, UK) including a stented pericardial valve, and in 19 patients with a xenopericardial conduit containing a stentless porcine valve. All patients underwent postoperative magnetic resonance imaging (MRI). A control group of seven patients allowed for comparison with native aortic root hemodynamics. RESULTS: Maximum flow-velocity above the aortic valve as one marker of compliance of the aortic root was slightly higher in patients with a Valsalva graft compared to native aortic roots (1.9 m/s versus 1.3 m/s, p = 0.001), but was significantly lower than in patients with the xenopericardial graft without neo-sinuses (1.3 m/s versus 2.4 m/s, p < 0.001). CONCLUSION: The pre-shaped bulges in the prosthetic Valsalva graft effectively mimic the native sinuses of Valsalva, improve compliance of the aortic root, and result in a more physiologic flow pattern, as demonstrated by postoperative MRI.

Estimación del riesgo sísmico en puerto príncipe (Haití)

Tras el devastador terremoto del 12 de enero de 2010 en Puerto Príncipe, Haití, las autoridades locales, numerosas ONGs y organismos nacionales e internacionales están trabajando en el desarrollo de estrategias para minimizar el elevado riesgo sísmico existente en el país. Para ello es necesario, en primer lugar, estimar dicho riesgo asociado a eventuales terremotos futuros que puedan producirse, evaluando el grado de pérdidas que podrían generar, para dimensionar la catástrofe y actuar en consecuencia, tanto en lo referente a medidas preventivas como a adopción de planes de emergencia. En ese sentido, este Trabajo Fin de Master aporta un análisis detallado del riesgo sísmico asociado a un futuro terremoto que podría producirse con probabilidad razonable, causando importantes daños en Puerto Príncipe. Se propone para ello una metodología de cálculo del riesgo adaptada a los condicionantes de la zona, con modelos calibrados empleando datos del sismo de 2010. Se ha desarrollado en el marco del proyecto de cooperación Sismo-Haití, financiado por la Universidad Politécnica de Madrid, que comenzó diez meses después del terremoto de 2010 como respuesta a una petición de ayuda del gobierno haitiano. El cálculo del riesgo requiere la consideración de dos inputs: la amenaza sísmica o movimiento esperado por el escenario definido (sismo de cierta magnitud y localización) y los elementos expuestos a esta amenaza (una clasificación del parque inmobiliario en diferentes tipologías constructivas, así como su vulnerabilidad). La vulnerabilidad de estas tipologías se describe por medio de funciones de daño: espectros de capacidad, que representan su comportamiento ante las fuerzas horizontales motivadas por los sismos, y curvas de fragilidad, que representan la probabilidad de que las estructuras sufran daños al alcanzar el máximo desplazamiento horizontal entre plantas debido a la mencionada fuerza horizontal. La metodología que se propone especifica determinadas pautas y criterios para estimar el movimiento, asignar la vulnerabilidad y evaluar el daño, cubriendo los tres estados del proceso. Por una parte, se consideran diferentes modelos de movimiento fuerte incluyendo el efecto local, y se identifican los que mejor ajustan a las observaciones de 2010. Por otra se clasifica el parque inmobiliario en diferentes tipologías constructivas, en base a la información extraída en una campaña de campo y utilizando además una base de datos aportada por el Ministerio de Obras Públicas de Haití. Ésta contiene información relevante de todos los edificios de la ciudad, resultando un total de 6 tipologías. Finalmente, para la estimación del daño se aplica el método capacidad-demanda implementado en el programa SELENA (Molina et al., 2010). En primer lugar, utilizado los datos de daño del terremoto de 2010, se ha calibrado el modelo propuesto de cálculo de riesgo sísmico: cuatro modelos de movimiento fuerte, tres modelos de tipo de suelo y un conjunto de funciones de daño. Finalmente, con el modelo calibrado, se ha simulado un escenario sísmico determinista correspondiente a un posible terremoto con epicentro próximo a Puerto Príncipe. Los resultados muestran que los daños estructurales serán considerables y podrán llevar a pérdidas económicas y humanas que causen un gran impacto en el país, lo que pone de manifiesto la alta vulnerabilidad estructural existente. Este resultado será facilitado a las autoridades locales, constituyendo una base sólida para toma de decisiones y adopción de políticas de prevención y mitigación del riesgo. Se recomienda dirigir esfuerzos hacia la reducción de la vulnerabilidad estructural - mediante refuerzo de edificios vulnerables y adopción de una normativa sismorresistente- y hacia el desarrollo de planes de emergencia. Abstract After the devastating 12 January 2010 earthquake that hit the city of Port-au-Prince, Haiti, strategies to minimize the high seismic risk are being developed by local authorities, NGOs, and national and international institutions. Two important tasks to reach this objective are, on the one hand, the evaluation of the seismic risk associated to possible future earthquakes in order to know the dimensions of the catastrophe; on the other hand, the design of preventive measures and emergency plans to minimize the consequences of such events. In this sense, this Master Thesis provides a detailed estimation of the damage that a possible future earthquake will cause in Port-au-Prince. A methodology to calculate the seismic risk is proposed, adapted to the study area conditions. This methodology has been calibrated using data from the 2010 earthquake. It has been conducted in the frame of the Sismo-Haiti cooperative project, supported by the Technical University of Madrid, which started ten months after the 2010 earthquake as an answer to an aid call of the Haitian government. The seismic risk calculation requires two inputs: the seismic hazard (expected ground motion due to a scenario earthquake given by magnitude and location) and the elements exposed to the hazard (classification of the building stock into building typologies, as well as their vulnerability). This vulnerability is described through the damage functions: capacity curves, which represent the structure performance against the horizontal forces caused by the seisms; and fragility curves, which represent the probability of damage as the structure reaches the maximum spectral displacement due to the horizontal force. The proposed methodology specifies certain guidelines and criteria to estimate the ground motion, assign the vulnerability, and evaluate the damage, covering the whole process. Firstly, different ground motion prediction equations including the local effect are considered, and the ones that have the best correlation with the observations of the 2010 earthquake, are identified. Secondly, the classification of building typologies is made by using the information collected during a field campaign, as well as a data base provided by the Ministry of Public Works of Haiti. This data base contains relevant information about all the buildings in the city, leading to a total of 6 different typologies. Finally, the damage is estimated using the capacity-spectrum method as implemented in the software SELENA (Molina et al., 2010). Data about the damage caused by the 2010 earthquake have been used to calibrate the proposed calculation model: different choices of ground motion relationships, soil models, and damage functions. Then, with the calibrated model, a deterministic scenario corresponding to an epicenter close to Port-au-Prince has been simulated. The results show high structural damage, and therefore, they point out the high structural vulnerability in the city. Besides, the economic and human losses associated to the damage would cause a great impact in the country. This result will be provided to the Haitian Government, constituting a scientific base for decision making and for the adoption of measures to prevent and mitigate the seismic risk. It is highly recommended to drive efforts towards the quality control of the new buildings -through reinforcement and construction according to a seismic code- and the development of emergency planning.

Experimental and Analytical Study of Masonry Infill Reinforced Concrete Frames Retrofitted with Steel Braces

In the present work a seismic retrofitting technique is proposed for masonry infilled reinforced concrete frames based on the replacement of infill panels by K-bracing with vertical shear link. The performance of this technique is evaluated through experimental tests. A simplified numerical model for structural damage evaluation is also formulated according to the notions and principles of continuum damage mechanics. The proposed model is calibrated with the experimental results. The experimental results have shown an excellent energy dissipation capacity with the proposed technique. Likewise, the numerical predictions with the proposed model are in good agreement with experimental results.

Ionoluminescence on α-quartz: mechanisms and modeling

Ionoluminescence of α - quartz exhibits two dominant emission bands peaking at 1.9 eV. (NBOHCs) and 2.7 eV (STEs. The evolution of the red emission yield does not show a correlation with the concentrations of neither the NBOHC nor with that of other color centers. The blue emission yield closely follows the amorphization kinetics independently measured by RBS/C spectrometry. A simple theoretical model has been proposed; it assumes that the formation and recombination of STEs are the primary event and both, the light emissions and the lattice structural damage are a consequence this phenomenon. The model leads to several simple mathematical equations that can be used to simulate the IL yields and provide a reasonable fit to experimental kinetic data.

A computational model coupling mechanics and electrophysiology in spinal cord injury

Traumatic brain injury and spinal cord injury have recently been put under the spotlight as major causes of death and disability in the developed world. Despite the important ongoing experimental and modeling campaigns aimed at understanding the mechanics of tissue and cell damage typically observed in such events, the differenti- ated roles of strain, stress and their corresponding loading rates on the damage level itself remain unclear. More specif- ically, the direct relations between brain and spinal cord tis- sue or cell damage, and electrophysiological functions are still to be unraveled. Whereas mechanical modeling efforts are focusing mainly on stress distribution and mechanistic- based damage criteria, simulated function-based damage cri- teria are still missing. Here, we propose a new multiscale model of myelinated axon associating electrophysiological impairment to structural damage as a function of strain and strain rate. This multiscale approach provides a new framework for damage evaluation directly relating neuron mechanics and electrophysiological properties, thus provid- ing a link between mechanical trauma and subsequent func- tional deficits.

Evaluación de la vulnerabilidad sísmica urbana basada en tipologías constructivas y disposición urbana de la edificación. Aplicación en la ciudad de Lorca, región de Murcia

Actualmente, diversos terremotos han puesto de manifiesto la importancia de planificar las ciudades y la gran influencia que tiene el comportamiento de los edificios como consecuencia de los resultados de pérdidas humanas y económicas. Ante la imposibilidad de evitar la ocurrencia de terremotos y de predecirlos con un margen pequeño de tiempo para tomar acciones a corto plazo, la reducción de la vulnerabilidad de los elementos expuestos es la medida más eficaz para prevenir los daños y para evitar el desastre. Existen varios estudios anteriores de Norman B. Green (1980), Teresa Guevara López (2009 y 2012) que recogen criterios ya generalizados dentro de la bibliografía sísmica y algunos aspectos procedentes de norma sísmicas precursoras en este campo (por ejemplo, las peruanas) para establecer inicialmente unos principios urbanístico-sísmicos. Además, varios proyectos relacionados con el riesgo sísmico, RisK-Ue (2003), SERAMAR (Lars Abrahamczyk et al., 2013) han desarrollado metodologías que clasifican la vulnerabilidad de los edificios teniendo en cuenta modificadores por comportamientos y configuraciones irregulares sísmicamente. El presente trabajo desarrolla una metodología empírica para identificar y caracterizar los parámetros urbanísticos que determinan una respuesta sísmica irregular de las edificaciones, graduar su relación con el daño tras un terremoto y poder así disminuir la vulnerabilidad sísmica de las ciudades. La metodología desarrollada en esta tesis doctoral se aplica en la ciudad de Lorca, Región de Murcia. Se realiza un trabajo de campo donde se clasifican los edificios según su tipología estructural y sus parámetros urbanísticos. A través de un estudio estadístico se analiza la correlación con el daño de las edificaciones tras el terremoto del 11 de mayo de 2011. Previamente se ha hecho una clasificación de los edificios según la clase de suelo en la que se encuentran según el Eurocódigo8 (Navarro et al, 2012). Por último, se aplica la metodología para obtener una estimación de la habitabilidad de los edificios en Lorca post sismo. Para esta clasificación se ha adoptado el criterio recogido en diversas recomendaciones internacionales, la mayoría de las cuales se basan en la documentación generada por el ATC- Applied Technology Council, distinguiendo entre edificios habitables (no daño-daño no estructural) y edificios no habitables (daño estructural). ABSTRACT Currently, various earthquakes have made clear first, the importance of city planning and secondly, the great influence that has the behaviour of buildings as a consequence of the results of human and economic losses. Faced with the impossibility of avoiding the occurrence of earthquakes and predicting its with a small margin of time to take action in the short term, the reduction of the vulnerability of exposed elements is the most effective measure to prevent damage and to prevent the disaster. There are several previous studies, Norman B. Green (1980), Teresa Guevara López (2009-2012) collecting criteria already widespread within the seismic bibliography and we can find some aspects from standard seismic precursor in this field (for example, the Peruvian) to initially establish urban - seismic principles. In addition, several projects related to seismic risk, RisK-EU (2003), SERAMAR (Lars Abrahamczyk et al., 2013) have developed methodologies that classify the vulnerability of buildings taking into account modifiers for behaviours and irregular configurations in seismical terms. This paper develops an empirical methodology to identify and characterize the irregular urban parameters seismically, graduate its relationship with the building damages after an earthquake and thus reduce the seismic vulnerability of cities. The methodology developed in this thesis applies in the city of Lorca, Region of Murcia. Fieldwork where buildings are classified according to their structural type and its urban performance parameters. Through a statistical study the correlation with damage of buildings is analyzed after the earthquake of May 11, 2011. Previously a classification of the buildings has been made according to the kind of soil according to the Eurocodigo 8 (Navarro et al, 2012). Finally, you get an estimate of the building habitability in Lorca. As a result, this classification adopted the criterion contained in various international recommendations, most of which are based on the documentation published by the ATC - Applied Technology Council, habitable buildings (not damage -damage non-structural) and non habitable buildings (structural damage).

A computational model coupling mechanics and electrophysiology in spinal cord injury

Traumatic brain injury and spinal cord injury have recently been put under the spotlight as major causes of death and disability in the developed world. Despite the important ongoing experimental and modeling campaigns aimed at understanding the mechanics of tissue and cell damage typically observed in such events, the differentiated roles of strain, stress and their corresponding loading rates on the damage level itself remain unclear. More specifically, the direct relations between brain and spinal cord tissue or cell damage, and electrophysiological functions are still to be unraveled. Whereas mechanical modeling efforts are focusing mainly on stress distribution and mechanistic-based damage criteria, simulated function-based damage criteria are still missing. Here, we propose a new multiscale model of myelinated axon associating electrophysiological impairment to structural damage as a function of strain and strain rate. This multiscale approach provides a new framework for damage evaluation directly relating neuron mechanics and electrophysiological properties, thus providing a link between mechanical trauma and subsequent functional deficits

Piezoelectric sensing and non-parametric statistical signal processing for health monitoring of hysteretic dampers used in seismic-resistant structures

The paper proposes a new application of non-parametric statistical processing of signals recorded from vibration tests for damage detection and evaluation on I-section steel segments. The steel segments investigated constitute the energy dissipating part of a new type of hysteretic damper that is used for passive control of buildings and civil engineering structures subjected to earthquake-type dynamic loadings. Two I-section steel segments with different levels of damage were instrumented with piezoceramic sensors and subjected to controlled white noise random vibrations. The signals recorded during the tests were processed using two non-parametric methods (the power spectral density method and the frequency response function method) that had never previously been applied to hysteretic dampers. The appropriateness of these methods for quantifying the level of damage on the I-shape steel segments is validated experimentally. Based on the results of the random vibrations, the paper proposes a new index that predicts the level of damage and the proximity of failure of the hysteretic damper

Does a neuroimmune interaction contribute to the genesis of painful peripheral neuropathies?

Painful peripheral neuropathies are precipitated by nerve injury from disease or trauma. All such injuries will be accompanied by an inflammatory reaction, a neuritis, that will mobilize the immune system. The role of the inflammation itself is difficult to determine in the presence of structural damage to the nerve. A method has been devised to produce a focal neuritis in the rat sciatic nerve that involves no more than trivial structural damage to the nerve. This experimental focal neuritis produces neuropathic pain sensations (heat- and mechano-hyperalgesia, and cold- and mechano-allodynia) in the ipsilateral hind paw. The abnormal pain sensations begin in 1–2 days and last for 4–6 days, with a subsequent return to normal. These results suggest that there is a neuroimmune interaction that occurs at the outset of nerve injury (and perhaps episodically over time in slow developing conditions like diabetic neuropathy) that produces neuropathic pain. The short duration of the phenomena suggest that they may prime the system for more slowly developing mechanisms of abnormal pain (e.g., ectopic discharge in axotomized primary afferent neurons) that underlie the chronic phase of painful neuropathy.

Copper-catalyzed oxidation of the recombinant SHa(29–231) prion protein

Metal-catalyzed oxidation may result in structural damage to proteins and has been implicated in aging and disease, including neurological disorders such as Alzheimer's disease and amyotrophic lateral sclerosis. The selective modification of specific amino acid residues with high metal ion affinity leads to subtle structural changes that are not easy to detect but may have dramatic consequences on physical and functional properties of the oxidized protein molecules. PrP contains a histidine-rich octarepeat domain that binds copper. Because copper-binding histidine residues are particularly prone to metal-catalyzed oxidation, we investigated the effect of this reaction on the recombinant prion protein SHaPrP(29–231). Using Cu2+/ascorbate, we oxidized SHaPrP(29–231) in vitro. Oxidation was demonstrated by liquid chromatography/mass spectrometry, which showed the appearance of protein species of higher mass, including increases in multiples of 16, characteristic of oxygen incorporation. Digestion studies using Lys C indicate that the 29–101 region, which includes the histidine-containing octarepeats, is particularly affected by oxidation. Oxidation was time- and copper concentration-dependent and was evident with copper concentrations as low as 1 μM. Concomitant with oxidation, SHaPrP(29–231) suffered aggregation and precipitation, which was nearly complete after 15 min, when the prion protein was incubated at 37°C with a 6-fold molar excess of Cu2+. These findings indicate that PrP, a copper-binding protein, may be particularly susceptible to metal-catalyzed oxidation and that oxidation triggers an extensive structural transition leading to aggregation.

Patterns of Stem Cell Divisions Contribute to Plant Longevity

The lifespan of plants ranges from a few weeks in annuals to thousands of years in trees. It is hard to explain such extreme longevity considering that DNA replication errors inevitably cause mutations. Without purging through meiotic recombination, the accumulation of somatic mutations will eventually result in mutational meltdown, a phenomenon known as Muller’s ratchet. Nevertheless, the lifespan of trees is limited more often by incidental disease or structural damage than by genetic aging. The key determinants of tree architecture are the axillary meristems, which form in the axils of leaves and grow out to form branches. The number of branches is low in annual plants, but in perennial plants iterative branching can result in thousands of terminal branches. Here, we use stem cell ablation and quantitative cell-lineage analysis to show that axillary meristems are set aside early, analogous to the metazoan germline. While neighboring cells divide vigorously, axillary meristem precursors maintain a quiescent state, with only 7–9 cell divisions occurring between the apical and axillary meristem. During iterative branching, the number of branches increases exponentially, while the number of cell divisions increases linearly. Moreover, computational modeling shows that stem cell arrangement and positioning of axillary meristems distribute somatic mutations around the main shoot, preventing their fixation and maximizing genetic heterogeneity. These features slow down Muller’s ratchet and thereby extend lifespan.

Quantitative assessment of aortic sclerosis using ultrasonic backscatter

Background. The development of therapeutic interventions to prevent progressive valve damage is more likely to limit the progression of structural damage to the aortic valve with normal function (aortic sclerosis [ASC]) than clinically apparent aortic stenosis. Currently, the ability to appreciate the progression of ASC is compromised by the subjective and qualitative evaluation of sclerosis severity. Methods: We sought to reveal whether the intensity of ultrasonic backscatter could be used to quantify sclerosis severity in 26 patients with ASC and 23 healthy young adults. images of the aortic valve were obtained in the parasternal long-axis view and saved in raw data format. Six square-shaped 11 X 11 pixel regions of interest were placed on the anterior and posterior leaflets, and calibrated backscatter values were obtained by subtracting the regions of interest in the blood pool from the averaged backscatter values obtained from the leaflets. Results. Mean ultrasonic backscatter values for sclerotic valves exceeded the results in normal valve tissue (16.3 +/- 4.4 dB vs 9.8 +/- 3.3 dB, P < .0001). Backscatter values were greater (22.0 +/- 3.5 dB) in a group of 6 patients with aortic stenosis. Within the sclerosis group, the magnitude of backscatter was directly correlated (P < .05) with a subjective sclerosis score, and with transvalvular pressure gradient. mean reproducibility was 2.4 +/- 1.8 dB (SD) between observers, and 2.3 +/- 1.7 dB (SD) between examinations. Conclusion: Measurement of backscatter from the valve leaflets of patients with ASC may be a feasible means of following the progression and treatment response of aortic sclerosis.

Predictors of osteoarthritis(OA) improvement in patients treated with Hylan G-F for knee OA.

Aim of study: Different criteria for treatment response were explored to identify predictors of OA improvement. Analyses were based on data from a previously reported 1-year randomized controlled trial of appropriate care with or without hylan G-F 20 in patients with knee OA. Methods: Five definitions of ‘‘patient responder’’ from baseline to month 12 were examined: at least 20% reduction in WOMAC pain score; at least 20% reduction in WOMAC pain score and at least 20% reduction in either the WOMAC stiffness or function score; OARSI responder criteria (Propositions A and B) for intra-articular drugs; and OMERACT-OARSI responder criteria (Proposition D). As an a posteriori analysis, multivariable logistic regression models for each definition of patient responder were developed using a forward selection method. The following variables were defined prior to modeling and considered in the model along with two-way interactions: age (O65 years), BMI, gender, X-ray grade (0, I, II vs III, IV), co-morbidity (1 or 2 conditions vs 3 or more), duration of OA in study knee (years), previous surgery of study knee, hylan G-F 20 injection technique, WOMAC pain, stiffness and function, and treatment group. Results: Hylan G-F 20 was a predictor of improvement for all patient responder definitions P ! 0.001; odds of improvement were 2.7 or higher for patients in the hylan G-F 20 group compared to appropriate care without hylan G-F 20. For three of the five patient responder definitions, X-ray grade was a predictor of improvement (P ! 0.10; lower X-ray grade increased the odds of improvement). For four of the five patient responder definitions, duration of OA was a predictor of improvement (P ! 0.10; shorter duration of OA increased the odds of improvement). Conclusion: Analyses showed that appropriate care with hylan G-F 20 is the dominant predictor of patient improvement. While high grade structural damage does not preclude a response, patients who are targeted early in the disease process when less structural damage has occurred, may have a greater chance of improvement.