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PubMed2001

[Characteristic perfusion pattern of osseous giant cell tumor in dynamic contrast-enhanced MRI].

PURPOSE: To describe the perfusion pattern of giant cell tumor (GCT) of bone with Gd-enhanced dynamic MR imaging. To compare time-intensity-curves in patients with local recurrence and postoperative alterations without recurrence. METHODS: Nine patients (5 women, 4 men) with GCT of bone underwent 19 dynamic MRI examinations. Mean age was 34 years (range 24-64 years). All diagnoses were proven by pathology. Dynamic contrast-enhanced MRI was performed at 1.0 T using T1-weighted gradient echo sequences. GCT was located in the distal radius (4x), tibia (3x), fibula (1x) and humeral head (1x). RESULTS: All giant cell tumors showed a uniform perfusion pattern with a steep slope and maximum intensity value followed by an early and rapid washout phase. The same pattern appeared in five local recurrences of GCT in four patients. In nine follow-up examinations without local recurrence dynamic MRI yielded in uncharacteristic perfusion patterns. CONCLUSION: These results demonstrate a uniform perfusion pattern of GCT of bone obtained by dynamic MRI. It is characterized by a steep slope followed by an early and rapid washout phase. This characteristic pattern can also be obtained in local recurrences. Dynamic contrast-enhanced MRI appears a helpful method for primary diagnosis of GCT of bone and detection of local recurrences after surgery.

Adult↗
PubMed2006

Is fall prevention by vitamin D mediated by a change in postural or dynamic balance?

INTRODUCTION: The objectives were:(1) to validate a quantitative balance assessment method for fall risk prediction; (2) to investigate whether the effect of vitamin D and calcium on the risk of falling is mediated through postural or dynamic balance, as assessed by this method. MATERIALS AND METHODS: A secondary analysis of a double blind randomized controlled trial was employed, which included 64 institutionalized elderly women with complete balance assessment (age range: 65-97; mean 25-hydroxyvitamin D levels: 16.4 ng/ml (SD +/-9.9). Participants received 1,200 mg calcium plus 800 IU cholecalciferol (n=33) or 1,200 mg calcium (n=31) per day over a 3-month treatment period. Using an electronic device attached to the lower back of the participant, balance was assessed as the degree of trunk angular displacement and angular velocity during a postural task (standing on two legs, eyes open, for 20 s) and a dynamic task (get up from a standard height chair with arm rests, sit down and then stand up again and remain standing). RESULTS: It was found that both postural and dynamic balance independently and significantly predicted the rate of falling within the 3-month follow-up. Vitamin D plus calcium reduced the rate of falls by 60% [relative risk (RR)=0.40; 95% CI: 0.17, 0.94] if compared with calcium alone. Once postural and dynamic balance were added to the regression analysis, they both attenuated the effect of vitamin D plus calcium on the rate of falls. For postural balance, the RR changed by 22% from 0.40 to 0.62 if angular displacement was added to the model, and by 9% from 0.40 to 0.49 if angular velocity was added. For dynamic balance, it changed by 1% from 0.40 to 0.41 if angular displacement was added, and by 14% from 0.40 to 0.54 if angular velocity was added. DISCUSSION: Thus, balance assessment using trunk angular displacement is a valid method for the prediction of falls in older women. Of the observed 60% reduction in the rate of falls by vitamin D plus calcium supplementation compared with calcium alone, up to 22% of the treatment effect was explained by a change in postural balance and up to 14% by dynamic balance.

Accidental Falls↗
PubMed2002

Innocuous cooling can produce nociceptive sensations that are inhibited during dynamic mechanical contact.

In a previous study of the heat grill illusion, sensations of burning and stinging were sometimes reported when the skin was cooled by as little as 2 degrees C. Informal tests subsequently indicated that these nociceptive sensations were experienced if cooling occurred when the stimulating thermode rested on the skin, but not when the thermode was cooled and then touched to the skin. In experiment 1 subjects judged the intensity of thermal (cold/warm) and nociceptive (burning/stinging) sensations when the volar surface of the forearm was cooled to 25 degrees C (1) via a static thermode (Static condition), or (2) via a cold thermode touched to the skin (Dynamic condition). The total area of stimulation was varied from 2.6 to 10.4 cm(2) to determine if the occurrence of nociceptive sensations depended upon stimulus size. Burning/stinging was rated 10.3 times stronger in the Static condition than in the Dynamic condition, and this difference did not vary significantly with stimulus size. In experiment 2, thermal and nociceptive sensations were measured during cooling to just 31 degrees, 29 degrees or 27 degrees C, and data were obtained on the frequency at which different sensation qualities were experienced. Stinging was the most frequently reported nociceptive quality in the Static condition, and stinging and burning were both markedly reduced in the Dynamic condition. In experiment 3 we tested the possibility that dynamic contact might have inhibited burning and stinging not because of mechanical contact per se, but rather because dynamic contact caused higher rates of cooling. However, varying cooling rate over a tenfold range (-0.5 degrees to -5.0 degrees /s) had no appreciable effect on the frequency of stinging and burning. Overall, the data show that mild cooling can produce nociceptive sensations that are suppressed under conditions of dynamic mechanical contact. The latter observation suggests that cold is perceived differently during active contact with objects than during passive heat loss to the environment. Hypotheses about the physiological basis of the nociceptive sensations at mild temperatures and their possible role in the phenomena of paradoxical heat and synthetic heat are discussed.

Adult↗
PubMed2004

Cerebellar damage produces context-dependent deficits in control of leg dynamics during obstacle avoidance.

It has been suggested that the cerebellum is an important contributor to CNS prediction and control of intersegmental dynamics during voluntary multijoint reaching movements. Leg movements subserve different behavioral goals, e.g., locomotion versus voluntary stepping, which may or may not be under similar dynamic control. The objective was to determine whether cerebellar leg hypermetria (excessive foot elevation) during obstacle avoidance in locomotion and voluntary stepping could be attributed to a particular deficit in appropriately controlling intersegmental dynamics. We compared the performance of eight individuals with cerebellar damage to eight healthy controls as they walked or voluntarily stepped in place over a small obstacle. Joint kinematics and dynamics were calculated during swing phase for both movement contexts. The kinematic analysis showed that hypermetria occurred during both walking and stepping and was associated with excessive knee flexion. When present, the amplitude of hypermetria was greater during stepping compared to walking. During stepping, subjects with cerebellar damage produced excessive knee flexor muscle torques and consequently overcompensated for interaction and gravitational torques normally used to decelerate the limb. During walking, the torque pattern was very similar to that of control subjects walking over a taller obstacle, and therefore might be a voluntary compensatory strategy to avoid tripping. Our results show that the extent of kinematic and dynamic abnormalities associated with cerebellar leg hypermetria is context-specific, with more fundamental abnormalities of leg dynamics being apparent during stepping as opposed to walking.

Adult↗
PubMed2004

Multijoint dynamics and postural stability of the human arm.

The goal of this study was to examine how the mechanical properties of the human arm are modulated during isometric force regulation tasks. Specifically, we examined whether the dynamic stability of the limb remained nearly invariant across a range of voluntarily generated endpoint forces and limb postures. Previous single joint studies have demonstrated that dynamic joint stability, as quantified via estimates of the joint damping ratio, is nearly invariant during isometric torque regulation tasks. However, the relevance of these findings to the control of multijoint posture has not been investigated previously. A similar degree of invariance at the multijoint level could suggest a fundamental property of the motor system that could be incorporated into the planning and execution of multijoint tasks. In this work, limb mechanics were quantified using estimates of dynamic endpoint stiffness, which characterizes the relationship between imposed displacements of limb posture and the forces opposing those displacements. Endpoint stiffness was estimated using a two-link robot operating in the horizontal plane at the height of each subject's glenohumeral joint. The robot was used to apply stochastic position perturbations to the arm and to measure the resulting forces. Endpoint stiffness dynamics were estimated nonparametrically and subsequently summarized using inertial, viscous and elastic parameters. We found that in the tasks studied, there was a differential modulation of endpoint elasticity and endpoint viscosity. Elasticity increased nearly linearly with increases in voluntary force generation while viscosity increased nonlinearly. This differential regulation resulted in limb dynamics that had a remarkably consistent damping ratio across all subjects and all tested conditions. These results emphasize the importance of considering the full dynamic response of a limb when investigating multijoint stability, and suggest that a minimal degree of limb stability is maintained over a wide range of force regulation tasks.

Adult↗
PubMed2005

Influence of age on dynamic position sense: evidence using a sequential movement task.

Age related changes to the nervous system are well documented. The main objectives of this study were to examine age-associated changes in dynamic position sense and relate these changes to measures of balance and physical function. Two groups of individuals (young <30 years; elderly >60 years) performed an upper extremity movement sequence triggered by a pre-determined target angle during passive rotations of the ankle joint at ten random velocities (10-90 degrees s(-1)). Balance was assessed with a series of timed standing tests. Physical function was assessed with the SF 36 questionnaire. Muscle activity was recorded from the ankle dorsiflexors and plantarflexors during the dynamic position tests. Increased error in the elderly group suggested that dynamic position sense declines with age. Moreover, this decline in dynamic position sense was associated with decreased balance and an impaired perception of physical function. The elderly also co-contracted the ankle plantarflexors and dorsiflexors during the proprioceptive testing, perhaps as a strategy to "gain up" spindle sensitivity. These findings suggest that impaired dynamic position sense of the ankle contributes to alterations in the overall physical function and balance in the elderly. Rehabilitative training methods that improve dynamic position sense of the ankles may improve physical function and balance in the elderly.

Adult↗
PubMed2005

Learning and recall of incremental kinematic and dynamic sensorimotor transformations.

Numerous studies have shown that when people encounter a sudden and novel sensorimotor transformation that alters perceived or actual movement, they gradually adapt and can later recall what they have learned if they encounter the transformation again. In this study, we tested whether retention and recall of learning is also observed when kinematic and dynamic transformations are introduced incrementally such that participants never experience large movement errors. Participants adapted their reaching movements to either a visuomotor rotation of hand position (kinematic transformation) or a rotary viscous force-field applied to the hand (dynamic transformation). These perturbations were introduced either incrementally or instantaneously. Thus, four groups of participants were tested with an incremental and an instantaneous group for both the kinematic and dynamic perturbations. To evaluate retention of learning, participants from all four groups were tested a day later on the same kinematic or dynamic perturbation presented instantaneously (at full strength). As expected, we found that subjects in the instantaneous group retained learning across days. We also found that, for both kinematic and dynamic perturbations, retention was equally good or better when the transformation was introduced incrementally. Because large and clearly detectable movement errors were not observed during adaptation to incremental perturbations, we conclude that such errors are not required for the learning and retention of internal models of kinematic and dynamic sensorimotor transformations.

Adolescent↗
PubMed1999

Differences in functional magnetic resonance imaging of sensorimotor cortex during static and dynamic finger flexion.

Functional magnetic resonance imaging (fMRI) studies of the human motor system have commonly used movement paradigms which contain a dynamic component; however, the relationship between the fMRI signal for motor tasks with and without a dynamic component is not known. We have investigated the relationship between the fMRI signal during a static finger flexion task and during dynamic finger flexion at 1-3 Hz, each at two levels of force (5% and 10% of maximum voluntary contraction). A small fMRI response could be recorded from only a few subjects during the static tasks. In contrast, a substantial fMRI response occurred during dynamic tasks in all subjects at both levels of force. The fMRI response was not significantly correlated with force or movement rate during the dynamic tasks. It is concluded that the factors responsible for generating an fMRI response are fundamentally different during steady contractions compared to those involving a dynamic component, and that the fMRI signal may be more sensitive to changes in the pattern of neural activation rather than the ongoing firing rate or extent of activation.

Adult↗
PubMedDate not supplied

Evaluation of hepatocellular carcinoma after treatment with transcatheter arterial chemoembolization: comparison of Lipiodol-CT, power Doppler sonography, and dynamic MRI.

BACKGROUND: The purpose of this study was to compare the ability of Lipiodol-computed tomography (CT), power Doppler (PD) sonography, and dynamic magnetic resonance imaging (MRI) in evaluating the therapeutic effect of transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC). METHODS: TACE was performed by injecting an emulsion consisting of Lipiodol and a chemotherapeutic drug, followed by gelatin sponge particles, into 54 patients with 84 HCC lesions. Five to 7 days later, Lipiodol-CT, PD sonography, and dynamic MRI were performed. Findings from the three modalities were correlated with relapse within 1 year after TACE. RESULTS: All lesions with blood flow on PD sonography or intratumoral enhancement on dynamic MRI relapsed regardless of the findings with Lipiodol-CT. None of the negatively enhanced lesions on dynamic MRI relapsed regardless of the Lipiodol-CT findings. However, the readers could not evaluate the contrast uptake in 14 lesions that were already hyperintense on the precontrast images. These cases were considered unsuitable for qualitative assessment and reduced the applicability of MRI to 83% of the examined lesions (70 of 84). Although PD sonography perfectly predicted relapse in superficial (0-5 cm from abdominal surface) lesions of the right hepatic lobe, blood flow in deep (>5 cm) or left lobe lesions was undetectable regardless of the occurrence of relapse. As a result, Lipiodol-CT displayed 76.0% sensitivity, 67.6% specificity, and 72.6% accuracy. The sensitivity, specificity, and accuracy of PD sonography were 34.0%, 100%, and 60.7%, respectively. In the 70 lesions in which evaluation was possible, dynamic MRI achieved 100% sensitivity, 100% specificity, and 100% accuracy. CONCLUSION: Of the three modalities, dynamic MRI was the best for evaluating the efficacy of TACE in the treatment of HCC. We also found that superficial lesions of the right lobe are good candidates for PD sonography. However, high signals on precontrast MR images, motion artifacts, and ultrasonic attenuation remain key limitations.

Aged↗
PubMed2005

Three-dimensional dynamic magnetic resonance angiography for the evaluation of radiosurgically treated cerebral arteriovenous malformations.

We assessed the value of three-dimensional (3D) dynamic magnetic resonance angiography (MRA) for the follow-up of patients with radiosurgically treated cerebral arteriovenous malformations (AVMs). Fifty-four patients with cerebral AVMs treated by radiosurgery (RS) were monitored using conventional catheter angiography (CCA) and 3D dynamic MRA with sensitivity encoding based on the parallel imaging. Cerebral AVM was qualitatively classified by two radiologists into one of five categories in terms of residual nidus size and persistence of early draining vein (I, >6 cm; II, 3-6 cm; III, <3 cm; IV, isolated early draining vein; V, complete obliteration). 3D MRA findings showed a good agreement with CCA in 40 cases (kappa=0.62). Of 23 nidus detected on CCA, 3D dynamic MRA showed 14 residual nidus. Of 28 occluded nidus on 3D dynamic MRA, 22 nidus were occluded on CCA. The sensitivity and specificity of 3D dynamic MRA for the detection of residual AVM were 81% and 100%. 3D dynamic MRA after RS may therefore be useful in association with MRI and can be repeated as long as opacification of the nidus or early venous drainage persists, one CCA remaining indispensable to affirm the complete occlusion at the end of follow-up.

Adult↗
PubMed2003

Prospective study of artificial anal sphincter and dynamic graciloplasty for severe anal incontinence.

BACKGROUND AND AIMS: Dynamic graciloplasty and artificial anal sphincter are two options for refractory incontinence, the efficacy of which was compared in a prospective study. PATIENTS AND METHODS: Between November 1966 and June 1998, 16 patients were operated on (artificial anal sphincter 8, dynamic graciloplasty 8). Four consecutive operations with each technique were performed by two colorectal surgeons (one initiated the study with the neosphincter and the other with dynamic graciloplasty). Two independent observers assessed postoperative results at 4-month intervals. Patients were followed up to January 2001, with a median (interquartile range) of 44 (13) months and 39 (15) months for the nesophincter and the dynamic graciloplasty, respectively. RESULTS: Fourteen patients had complications. In the immediate postoperative period; there were eight cases of wound healing-related problems (four in the graciloplasty group). Perineal infection occurred in one patient in the graciloplasty group. At follow-up there were 11 complications (6 in the neosphincter group). Four patients undergoing neosphincter implantation had erosion or pain at the cuff site and had the implant removed (a new device was reimplanted in one). Four patients undergoing dynamic graciloplasty had the stimulator removed. Postoperatively the neosphincter was associated with a significantly lower score on the continence grading scale of the Cleveland Clinic Florida than graciloplasty. CONCLUSION: The artificial anal sphincter is a more convenient technique than dynamic graciloplasty for institutions treating small number of patients. However, technical failures and complications during follow-up that require reoperation are very high in both types of treatments.

Adolescent↗
PubMed2003

Activity dynamics and propagation of synchronous spiking in locally connected random networks.

Random network models have been a popular tool for investigating cortical network dynamics. On the scale of roughly a cubic millimeter of cortex, containing about 100,000 neurons, cortical anatomy suggests a more realistic architecture. In this locally connected random network, the connection probability decreases in a Gaussian fashion with the distance between neurons. Here we present three main results from a simulation study of the activity dynamics in such networks. First, for a broad range of parameters these dynamics exhibit a stationary state of asynchronous network activity with irregular single-neuron spiking. This state can be used as a realistic model of ongoing network activity. Parametric dependence of this state and the nature of the network dynamics in other regimes are described. Second, a synchronous excitatory stimulus to a fraction of the neurons results in a strong activity response that easily dominates the network dynamics. And third, due to that activity response an embedding of a divergent-convergent feed-forward subnetwork (as in synfire chains) does not naturally lead to a stable propagation of synchronous activity in the subnetwork; this is in contrast to our earlier findings in isolated subnetworks of that type. Possible mechanisms for stabilizing the interplay of volleys of synchronous spikes and network dynamics by specific learning rules or generalizations of the subnetworks are discussed.

Action Potentials↗
PubMed2001

Learning the dynamics of reaching movements results in the modification of arm impedance and long-latency perturbation responses.

Some characteristics of arm movements that humans exhibit during learning the dynamics of reaching are consistent with a theoretical framework where training results in motor commands that are gradually modified to predict and compensate for novel forces that may act on the hand. As a first approximation, the motor control system behaves as an adapting controller that learns an internal model of the dynamics of the task. It approximates inverse dynamics and predicts motor commands that are appropriate for a desired limb trajectory. However, we had previously noted that subtle motion characteristics observed during changes in task dynamics challenged this simple model and raised the possibility that adaptation also involved sensory-motor feedback pathways. These pathways reacted to sensory feedback during the course of the movement. Here we hypothesize that adaptation to dynamics might also involve a modification of how the CNS responds to sensory feedback. We tested this through experiments that quantified how the motor system's response to errors during voluntary movements changed as it adapted to dynamics of a force field. We describe a nonlinear approach that approximates the impedance of the arm, i.e., force response as a function of arm displacement trajectory. We observe that after adaptation, the impedance function changes in a way that closely matches and counters the effect of the force field. This is particularly prominent in the long-latency (> 100 ms) component of response to perturbations. Therefore, it appears that practice not only modifies the internal model with which the brain generates motor commands that initiate a movement, but also the internal model with which sensory feedback is integrated with the ongoing descending commands in order to respond to error during the movement.

Adult↗
PubMed2006

Construction of fibroblast-collagen gels with orientated fibrils induced by static or dynamic stress: toward the fabrication of small tendon grafts.

As a step toward the fabrication of small tendon grafts, fibroblast-collagen gels were constructed with orientated fibrils induced by static or dynamic loading. Three groups of gel samples, each consisting of 1.0 x 10(6) fibroblasts and 2 mg type I collagen, were fabricated: freely contracted gels formed the control group; contraction-directed gels made up the static group (the gel contraction was directed perpendicular to an axis made by two anchors buried in the gels so that the constraint stress exerted by the two anchors was imposed on the gel); and for the dynamic group, a specific loading pattern (free contraction followed by cyclic stretching using a tensile bioreactor) was employed. Mechanical properties were evaluated by means of the uniaxial tension test. The gels of the static group had an ultimate stress of 350 +/- 43.6 kPa and a material modulus of 548.8 +/- 61.6 kPa, which were almost 5.2 times and 15.6 times, respectively, greater than those of the controls. The dynamic gels had an ultimate stress of 256.8 +/- 80.7 kPa and a material modulus of 118.6 +/- 23.5 kPa. These results show that the ultimate stress and material modulus of the static samples are much greater than those of the dynamic samples, which is the opposite of our expectations. Therefore, studies under other dynamic loading patterns and long-term culture are needed to clarify whether dynamic loading is superior to static loading.

Bioreactors↗
PubMed2002

Long-term efficacy of dynamic graciloplasty for fecal incontinence.

PURPOSE: Patients with end-stage fecal incontinence in whom all standard medical and surgical treatment has failed or is not expected to be effective can be treated by dynamic graciloplasty. The aim of this study was to review the long-term efficacy data. METHODS: Success was defined as a greater than 50 percent decrease in the frequency of incontinent episodes. Measured physiologic parameters included enema retention time and the difference in resting and squeezing pressures with and without stimulation. Measured quality-of-life parameters included the Medical Outcomes Study Short Form 36 Health Status Questionnaire, a Fecal Incontinence TyPE Specification, the Zung Self-Rating Depression Scale, the "state" portion of the State-Trait Anxiety Inventory, and the Visual Analog Scale, which were administered at baseline and through follow-up. Independent monitors collected data as part of a multicenter trial for patients who underwent dynamic graciloplasty from May 1993 to November 1999. RESULTS: There were 129 patients entered in the study, 115 of whom met eligibility criteria and were included in the efficacy outcome analysis. Twenty-seven patients entered the study with a preexisting functioning stoma; the remaining 88 patients did not have a functioning stoma at the time of enrollment. Success was achieved in 62 percent of nonstoma patients at 12 months; these results were sustained at 18-month and 24-month follow-up assessments (55 and 56 percent, respectively). The success rate in the stoma patients increased from 37.5 percent (9 of 24 patients) at 12 months to 62 percent (13 of 21 patients) at 18 months and was 43 percent at 24 months (9 of 21 patients), which reflects the increased number of patients whose stomas were closed. Although the measured physiologic continence parameters generally improved, these changes did not correlate with continence outcome. The group of patients (stoma and nonstoma) who underwent dynamic graciloplasty showed statistically significant improvements in quality of life as measured by Medical Outcomes Study Short Form 36 physical function (P = 0.006) and social functioning (P = 0.02) assessment. CONCLUSIONS: Dynamic graciloplasty was successful in the majority of patients with end-stage fecal incontinence. This result was usually achieved by 12 months after surgery in patients who did not have stomas and by 18 months in patients who had stomas at the time of dynamic graciloplasty surgery. These various improvements conferred by dynamic graciloplasty persisted during the two-year follow-up.

Adolescent↗
PubMed2005

Residue specific ribose and nucleobase dynamics of the cUUCGg RNA tetraloop motif by MNMR 13C relaxation.

The dynamics of the nucleobase and the ribose moieties in a 14-nt RNA cUUCGg hairpin-loop uniformly labeled with 13C and 15N were studied by 13C spin relaxation experiments. R1, R1rho and the 13C-[1H] steady-state NOE of C6 and C1' in pyrimidine and C8 and C1' in purine residues were obtained at 298 K. The relaxation data were analyzed by the model-free formalism to yield dynamic information on timescales of pico-, nano- and milli-seconds. An axially symmetric diffusion tensor with an overall rotational correlation time tau(c) of 2.31 +/- 0.13 ns and an axial ratio of 1.35 +/- 0.02 were determined. Both findings are in agreement with hydrodynamic calculations. For the nucleobase carbons, the validity of different reported 13C chemical shift anisotropy values (Stueber, D. and Grant, D. M., 2002 J. Am. Chem. Soc. 124, 10539-10551; Fiala et al., 2000 J. Biomol. NMR 16, 291-302; Sitkoff, D. and Case, D. A., 1998 Prog. NMR Spectroscopy 32, 165-190) is discussed. The resulting dynamics are in agreement with the structural features of the cUUCGg motif in that all residues are mostly rigid (0.82 < S2 < 0.96) in both the nucleobase and the ribose moiety except for the nucleobase of U7, which is protruding into solution (S2 = 0.76). In general, ribose mobility follows nucleobase dynamics, but is less pronounced. Nucleobase dynamics resulting from the analysis of 13C relaxation rates were found to be in agreement with 15N relaxation data derived dynamic information (Akke et al., 1997 RNA 3, 702-709).

Base Sequence↗
PubMed2005

Iron responsive element RNA flexibility described by NMR and isotropic reorientational eigenmode dynamics.

The first example of the application of reorientational eigenmode dynamics (RED) to RNA is shown here for the small and floppy Iron Responsive Element (IRE) RNA hairpin. Order parameters calculated for bases and riboses from a 12 ns molecular dynamics trajectory are compared to experimentally determined order parameters from 13C-1H NMR relaxation experiments, and shown to be in qualitative agreement. Given the small size of the IRE hairpin and its very flexible loop, isotropic RED (iRED) was also used to analyze the trajectory in order to describe its dynamic motions. iRED analysis shows that the global and internal dynamics of the IRE are not rigorously separable, which will result in inaccurate experimental order parameters. In addition, the iRED analysis described the many correlated motions that comprise the dynamics of the IRE RNA. The combined use of NMR relaxation, RED, and iRED provide a uniquely detailed description of IRE RNA dynamics.

Magnetic Resonance Spectroscopy↗
PubMed2006

A non-linear mixed effect dynamic model incorporating prior exposure and adherence to treatment to describe long-term therapy outcome in HIV-patients.

Long term therapy with antiretroviral agents in HIV-infected patients often result in failure to suppress the virus load. Imperfect adherence to prescribed antiviral drugs is an important factor explaining the resurgence of virus. A better understanding of the factors responsible for the virological failure is important for the development of new treatment strategies. Many complex non-linear models have been developed to describe and simulate the dynamics of HIV-1 virus. Those complicated viral dynamic models have not been used in clinical trials to estimate HIV dynamics parameters, due to their complexity, until the recent development of simplification and approximation techniques. The estimation of the parameters associated with the dynamics from real data has been mostly limited to linearized models that can only explain the decay (suppression) of the virus following antiviral treatment. Moreover, no complete characterization of typical clinical data in terms of inter-subject variability and identification of important covariates effecting HIV-1 dynamics has been attempted. The objective of our paper was to develop a hierarchical non-linear mixed effect model characterizing inter-subject variability in the long-term response to treatment of HIV-1 RNA, and show how the model can be used to quantify the effect of important covariates, such as physiological variables, adherence to treatment or previous exposure to treatment, on the dynamics of HIV-1 RNA. As an example we report the analysis of AIDS clinical trial data from AACTG 398, which shows that patients with previous exposure to treatment show faster death rates for HIV-1, and that higher adherence to treatment is associated with lower reproductive ratio.

Algorithms↗