RNA-based next-generation sequencing (RNA-Seq) provides a tremendous amount of new information regarding gene and transcript structure, expression and regulation. This is particularly true for non-coding RNAs where whole transcriptome analyses have revealed that the much of the genome is transcribed and that many non-coding transcripts have widespread functionality. However, uniform resources for raw, cleaned and processed RNA-Seq data are sparse for most organisms and this is especially true for non-human primates (NHPs). Here, we describe a large-scale RNA-Seq data and analysis infrastructure, the NHP reference transcriptome resource (http://nhprtr.org); it presently hosts data from12 species of primates, to be expanded to 15 species/subspecies spanning great apes, old world monkeys, new world monkeys and prosimians. Data are collected for each species using pools of RNA from comparable tissues. We provide data access in advance of its deposition at NCBI, as well as browsable tracks of alignments against the human genome using the UCSC genome browser. This resource will continue to host additional RNA-Seq data, alignments and assemblies as they are generated over the coming years and provide a key resource for the annotation of NHP genomes as well as informing primate studies on evolution, reproduction, infection, immunity and pharmacology.
Instability is a significant concern in total hip arthroplasty, particularly when there is structural compromise of the capsule due to pre-existing pathology or due to necessities of surgical approach. An experimentally grounded fiber-direction-based finite element model of the hip capsule was developed, and was integrated with an established three-dimensional model of impingement/dislocation. Model validity was established by close similarity to results from a cadaveric experiment in a servohydraulic hip simulator. Parametric computational runs explored effects of graded levels of capsule thickness, of regional detachment from the capsule’s femoral or acetabular insertions, of surgical incisions of capsule substance, and of capsule defect repairs. Depending strongly upon the specific site, localized capsule defects caused varying degrees of construct stability compromise, with several specific situations involving over 60% decrement in dislocation resistance. Construct stability was returned substantially toward intact-capsule levels following well conceived repairs, although the suture sites involved were often at substantial risk of failure. These parametric model results underscore the importance of retaining or robustly repairing capsular structures in total hip arthroplasty, in order to maximize overall construct stability.
Total hip arthroplasty; hip capsule; finite element analysis; suture failure
Biological soft tissues and cells may be subjected to mechanical as well as chemical (osmotic) loading under their natural physiological environment or various experimental conditions. The interaction of mechanical and chemical effects may be very significant under some of these conditions, yet the highly nonlinear nature of the set of governing equations describing these mechanisms poses a challenge for the modeling of such phenomena. This study formulated and implemented a finite element algorithm for analyzing mechano-chemical events in neutral deformable porous media under finite deformation. The algorithm employed the framework of mixture theory to model the porous permeable solid matrix and interstitial fluid, where the fluid consists of a mixture of solvent and solute. A special emphasis was placed on solute-solid matrix interactions, such as solute exclusion from a fraction of the matrix pore space (solubility) and frictional momentum exchange that produces solute hindrance and pumping under certain dynamic loading conditions. The finite element formulation implemented full coupling of mechanical and chemical effects, providing a framework where material properties and response functions may depend on solid matrix strain as well as solute concentration. The implementation was validated using selected canonical problems for which analytical or alternative numerical solutions exist. This finite element code includes a number of unique features that enhance the modeling of mechano-chemical phenomena in biological tissues. The code is available in the public domain, open source finite element program FEBio (http://mrl.sci.utah.edu/software).
The relatively high incidence of labral tears among patients presenting with hip pain suggests that the acetabular labrum is often subjected to injurious loading in vivo. However, it is unclear whether the labrum participates in load transfer across the joint during activities of daily living. This study examined the role of the acetabular labrum in load transfer for hips with normal acetabular geometry and acetabular dysplasia using subject-specific finite element analysis. Models were generated from volumetric CT data and analyzed with and without the labrum during activities of daily living. The labrum in the dysplastic model supported 4-11% of the total load transferred across the joint, while the labrum in the normal model supported only 1-2% of the total load. Despite the increased load transferred to the acetabular cartilage in simulations without the labrum, there were minimal differences in cartilage contact stresses. This was because the load supported by the cartilage correlated to the cartilage contact area. A higher percentage of load was transferred to the labrum in the dysplastic model because the femoral head achieved equilibrium near the lateral edge of the acetabulum. The results of this study suggest that the labrum plays a larger role in load transfer and joint stability in hips with acetabular dysplasia than in hips with normal acetabular geometry.
acetabular labrum; hip; cartilage mechanics; finite element; dysplasia
Studies of behavioral weight loss intervention in psychotic patients are sparse and its efficacy compared to other obese patients is unknown. Therefore, we compared the effect of a cognitive-behavioral weight loss intervention in obese subjects with psychotic disorders, other psychiatric diagnoses and without psychiatric disorders.
12-month, naturalistic study of weekly group or individual cognitive-behavioral weight management in 222 consecutively enrolled obese patients (body mass index (BMI):43.7±9.6) with psychotic-spectrum disorders (PSD, n=47), other psychiatric disorders (OPD, n=49) and no psychiatric disorder (NPD, n=126).
PSD patients had greater treatment persistence (48.9%) and longer treatment duration (8.7±4.4 months) than OPD (22.4%, 5.4±4.3 months) and NPD (22.2%, 4.9±4.7 months) patients (p’s<.01, number-needed-to-treat (NNT)=3). In last-observation-carried-forward analyses, PSD patients had greater percent baseline weight loss at 12 months (5.1±9.3%) than OPD and NPD patients (2.7±5.5% and 2.4±6.3%); greater percent BMI loss at 9 and 12 months than both groups (p’s<.05), and greater BMI loss at 9 months (2.1±3.5) and 12 months (2.3±4.1) than NPD patients (1.1±2.3 and 1.2±2.4). Furthermore, weight loss ≥5%, occurred in 42.6% of PSD patients vs. 18.4% and 23.0% in OPD and NPD patients (p’s<.01, NNT=5 and 6). The strongest weight loss predictor was treatment duration (β=.51–.54, p<.001). Attrition was predicted by NPD (p=.001) and OPD group status (p=.036), lower proportion of group sessions (p=.002), higher depression (p=.028), and lower baseline BMI (p=0.030).
Psychosis-spectrum disorder patients had greater weight loss than other obese patients. Non-adherence and depression should be targeted to enhance weight loss success.
Obesity; Weight Management Program; Weight Loss; Attrition; Psychosis
We prospectively collected clinical data during the period 2001–2006 on 60 hips with symptomatic femoroacetabular impingement that had radiographic evidence of acetabular retroversion defined as a crossover sign on an adequate anteroposterior radiograph or retroversion on magnetic resonance imaging or computed tomography. Our treatment algorithm for acetabular retroversion used measurements of acetabular coverage (lateral center edge angle and the posterior wall sign) and condition of acetabular cartilage to direct treatment of acetabular retroversion. The algorithm directed the surgeon to perform a periacetabular-osteotomy (PAO) in 30 hips and in 30 hips a surgical-dislocation and osteochondroplasty (SDO) of the femoral head-neck junction and acetabular rim. HHS and Tönnis radiographic grading were collected preoperatively and at latest followup. The HHS improved from 52 to 90 in the hips treated with SDO and 72 to 91 in the hips treated with PAO, with an overall survivorship of 96% at four years. Patient follow-up averaged 46 months (range 24–75). Elimination of the crossover sign and correction of the posterior wall sign occurred in over 90% of all patients when present. The results indicate that hips with acetabular retroversion, deficient posterior and/or lateral acetabular coverage and intact hyaline cartilage can be effectively treated with acetabular reorientation while retroverted hips with anterior over-coverage but sufficient posterior coverage are effectively treated with osteochondroplasty of the acetabulum and proximal femur.
Background and purpose
Acetabular retroversion may result in anterior acetabular over-coverage and posterior deficiency. It is unclear how standard radiographic measures of retroversion relate to measurements from 3D models, generated from volumetric CT data. We sought to: (1) compare 2D radiographic measurements between patients with acetabular retroversion and normal control subjects, (2) compare 3D measurements of total and regional femoral head coverage between patients and controls, and (3) quantify relationships between radiographic measurements of acetabular retroversion to total and regional coverage of the femoral head.
Patients and methods
For 16 patients and 18 controls we measured the extrusion index, crossover ratio, acetabular angle, acetabular index, lateral center edge angle, and a new measurement termed the “posterior wall distance”. 3D femoral coverage was determined from volumetric CT data using objectively defined acetabular rim projections, head-neck junctions, and 4 anatomic regions. For radiographic measurements, intra-observer and inter-observer reliabilities were evaluated and associations between 2D radiographic and 3D model-based measures were determined.
Compared to control subjects, patients with acetabular retroversion had a negative posterior wall distance, increased extrusion index, and smaller lateral center edge angle. Differences in the acetabular index between groups approached statistical significance. The acetabular angle was similar between groups. Acetabular retroversion was associated with a slight but statistically significant increase in anterior acetabular coverage, especially in the anterolateral region. Retroverted hips had substantially less posterior coverage, especially in the posterolateral region.
We found that a number of 2D radiographic measures of acetabular morphology were correlated with 3D model-based measures of total and regional femoral head coverage. These correlations may be used to assist in the diagnosis of retroversion and for preoperative planning.
Computational techniques and software for the analysis of problems in mechanics have naturally moved from their origins in the traditional engineering disciplines to the study of cell, tissue and organ biomechanics. Increasingly complex models have been developed to describe and predict the mechanical behavior of such biological systems. While the availability of advanced computational tools has led to exciting research advances in the field, the utility of these models is often the subject of criticism due to inadequate model verification and validation. The objective of this review is to present the concepts of verification, validation and sensitivity studies with regard to the construction, analysis and interpretation of models in computational biomechanics. Specific examples from the field are discussed. It is hoped that this review will serve as a guide to the use of verification and validation principles in the field of computational biomechanics, thereby improving the peer acceptance of studies that use computational modeling techniques.
Verification; Validation; Sensitivity Studies; Computational Modeling; Biomechanics; Review
Porous-permeable tissues have often been modeled using porous media theories such as the biphasic theory. This study examines the equivalence of the short-time biphasic and incompressible elastic responses for arbitrary deformations and constitutive relations from first principles. This equivalence is illustrated in problems of unconfined compression of a disk, and of articular contact under finite deformation, using two different constitutive relations for the solid matrix of cartilage, one of which accounts for the large disparity observed between the tensile and compressive moduli in this tissue. Demonstrating this equivalence under general conditions provides a rationale for using available finite element codes for incompressible elastic materials as a practical substitute for biphasic analyses, so long as only the short-time biphasic response is sought. In practice, an incompressible elastic analysis is representative of a biphasic analysis over the short-term response
δt≪Δ2/‖C4‖||K||, where Δ is a characteristic dimension,
C4 is the elasticity tensor and K is the hydraulic permeability tensor of the solid matrix. Certain notes of caution are provided with regard to implementation issues, particularly when finite element formulations of incompressible elasticity employ an uncoupled strain energy function consisting of additive deviatoric and volumetric components.
The anterior-inferior glenohumeral capsule is the primary passive stabilizer to the glenohumeral joint during anterior dislocation. Physical examinations following dislocation are crucial for proper diagnosis of capsule pathology; however, they are not standardized for joint position which may lead to misdiagnoses and poor outcomes. To suggest joint positions for physical examinations where the stability provided by the capsule may be consistent among patients, the objective of this study was to evaluate the distribution of maximum principal strain on the anterior-inferior capsule using two validated subject-specific finite element models of the glenohumeral joint at clinically relevant joint positions. The joint positions with 25 N anterior load applied at 60° of glenohumeral abduction and 10°, 20°, 30° and 40° of external rotation resulted in distributions of strain that were similar between shoulders (r2 ≥ 0.7). Furthermore, those positions with 20° to 40° of external rotation resulted in capsule strains on the glenoid side of the anterior band of the inferior glenohumeral ligament that were significantly greater than in all other capsule regions. These findings suggest that anterior stability provided by the anterior-inferior capsule may be consistent among subjects at joint positions with 60° of glenohumeral abduction and a mid-range (20° to 40°) of external rotation, and that the glenoid side has the greatest contribution to stability at these joint positions. Therefore, it may be possible to establish standard joint positions for physical examinations that clinicians can use to effectively diagnose pathology in the anterior-inferior capsule following dislocation and lead to improved outcomes.
shoulder; glenohumeral joint; finite element models; ligament; strain
The structural organization of biological tissues and cells often produces anisotropic transport properties. These tissues may also undergo large deformations under normal function, potentially inducing further anisotropy. A general framework for formulating constitutive relations for anisotropic transport properties under finite deformation is lacking in the literature. This study presents an approach based on representation theorems for symmetric tensor-valued functions and provides conditions to enforce positive semi-definiteness of the permeability or diffusivity tensor. Formulations are presented which describe materials that are orthotropic, transversely isotropic, or isotropic in the reference state, and where large strains induce greater anisotropy. Strain-induced anisotropy of the permeability of a solid-fluid mixture is illustrated for finite torsion of a cylinder subjected to axial permeation. It is shown that, in general, torsion can produce a helical flow pattern, rather than the rectilinear pattern observed when adopting a more specialized, unconditionally isotropic spatial permeability tensor commonly used in biomechanics. The general formulation presented in this study can produce both affine and non-affine reorientation of the preferred directions of material symmetry with strain, depending on the choice of material functions. This study addresses a need in the biomechanics literature by providing guidelines and formulations for anisotropic strain-dependent transport properties in porous-deformable media undergoing large deformations.
Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4+ T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.
Recent advances in sequencing technology now allow the measurement of effectively all the RNA in a cell. This approach is especially useful for studying models of virus infection, as it allows the simultaneous measurement of both host and viral RNA. Using next-generation sequencing (NGS), we measured changes in total mRNA from a HIV-infected T cell line. To our knowledge, this is the first application of this technology to the investigation of HIV-host interactions involving intact HIV. We directly measured the amount of viral mRNA in infected cells and detected novel viral RNA splice variants and changes in the host expression of noncoding RNA species. We also detected small changes in T cell activation and other host processes during the early stages of viral replication that increased near the peak of viral replication, providing new candidate biomarkers of T cell death.
Dermatan and chondroitin sulfate glycosaminoglycans (GAGs) comprise over 90% of the GAG content in ligament. Studies of their mechanical contribution to soft tissues have reported conflicting results. Measuring the transient compressive response and biphasic material parameters of the tissue may elucidate the contributions of GAGs to the viscoelastic response to deformation. The hypotheses of the current study were that digestion of sulfated GAGs would decrease compressive stress and aggregate modulus while increasing the permeability of porcine medial collateral ligament (MCL). Confined compression stress relaxation experiments were carried out on porcine MCL and tissue treated with chondroitinase ABC (ChABC). Results were fit to a biphasic constitutive model to derive permeability and aggregate modulus. Bovine articular cartilage was used as a benchmark tissue to verify that the apparatus provided reliable results. GAG digestion removed up to 88% of sulfated GAGs from the ligament. Removal of sulfated GAGs increased the permeability of porcine MCL nearly 6-fold versus control tissues. Peak stress decreased significantly. Bovine articular cartilage exhibited the typical reduction of GAG content and resultant decreases in stress and modulus and increases in permeability with ChABC digestion. Given the relatively small amount of GAG in ligament (<1% of tissue dry weight) and the significant change in peak stress and permeability upon removal of GAGs, sulfated GAGs may play a significant role in maintaining the apposition of collagen fibrils in the transverse direction, thus supporting dynamic compressive loads experienced by the ligament during complex joint motion.
ligament; permeability; glycosaminoglycan; chondroitinase; stress relaxation
This study formulates and implements a finite element contact algorithm for solid-fluid (biphasic) mixtures, accommodating both finite deformation and sliding. The finite element source code is made available to the general public.
The algorithm uses a penalty method regularized with an augmented Lagrangian method to enforce the continuity of contact traction and normal component of fluid flux across the contact interface. The formulation addresses the need to automatically enforce free-draining conditions outside of the contact interface. The formulation addresses the need to automatically enforce free-draining conditions outside of the contact interface.
The accuracy of the implementation is verified using contact problems for which exact solutions are obtained by alternative analyses. Illustrations are also provided that demonstrate large deformations and sliding under configurations relevant to biomechanical applications such as articular contact.
This study addresses an important computational need in the biomechanics of porous-permeable soft tissues. Placing the source code in the public domain provides a useful resource to the biomechanics community.
Computational models may have the ability to quantify the relationship between hip morphology, cartilage mechanics and osteoarthritis. Most models have assumed the hip joint to be a perfect ball and socket joint and have neglected deformation at the interface between bone/cartilage. The objective of this study was to analyze finite element (FE) models of hip cartilage mechanics with varying degrees of simplified geometry and a model with a rigid bone material assumption to elucidate the effects on predictions of cartilage stress. A previously validated subject-specific FE model of a cadaveric hip joint was used as the basis for the models. Geometry for the bone/cartilage interface was either: 1) subject-specific (i.e. irregular), 2) spherical, or 3) a rotational conchoid. Cartilage was assigned either a varying (irregular) or constant thickness (smoothed). Loading conditions simulated walking, stair climbing and descending stairs. FE predictions of contact stress for the simplified models were compared with predictions from the subject-specific model. Both spheres and conchoids provided a good approximation of native hip joint geometry (average fitting error ~0.5 mm). However, models with spherical/conchoid bone geometry and smoothed articulating cartilage surfaces grossly underestimated peak and average contact pressures (50% and 25% lower, respectively) and overestimated contact area when compared to the subject-specific FE model. Models incorporating subject-specific bone geometry with smoothed articulating cartilage also underestimated pressures and predicted evenly distributed patterns of contact. The model with rigid bones predicted much higher pressures than the subject-specific model with deformable bones. The results demonstrate that simplifications to the geometry of the bone/cartilage interface, cartilage surface and bone material properties can have a dramatic effect on the predicted magnitude and distribution of cartilage contact pressures in the hip joint.
Hip; Finite Element; Biomechanics; Sphere; Conchoid; Boundary Conditions; Cartilage Pressures
Experimental measurements of the Poisson’s ratio in tendon and ligament tissue greatly exceed the isotropic limit of 0.5. This is indicative of volume loss during tensile loading. The microstructural origin of the large Poisson’s ratios is unknown. It was hypothesized that a helical organization of fibrils within a fiber would result in a large Poisson’s ratio in ligaments and tendons, and that this helical organization would be compatible with the crimped nature of these tissues, thus modeling their classic nonlinear stress strain behavior. Micromechanical finite element models were constructed to represent crimped fibers with a super helical organization, composed of fibrils embedded within a matrix material. A homogenization procedure was performed to determine both the effective Poisson’s ratio and the Poisson function. The results showed that helical fibril organization within a crimped fiber was capable of simultaneously predicting large Poisson’s ratios and the nonlinear stress strain behavior seen experimentally. Parametric studies revealed that the predicted Poisson’s ratio was strongly dependent on the helical pitch, crimp angle and the material coefficients. The results indicated that, for physiologically relevant parameters, the models were capable of predicting the large Poisson’s ratios seen experimentally. It was concluded that helical organization within a crimped fiber can produce both the characteristic nonlinear stress strain behavior and large Poisson’s ratios, while fiber crimp alone could only account for the nonlinear stress-strain behavior.
Ligament; Micromechanical; Poisson’s Ratio; Finite Element; Helical; Fiber; Tendon
Effective tissue prevascularization depends on new vessel growth and subsequent progression of neovessels into a stable microcirculation. Isolated microvessel fragments in a collagen-based microvascular construct (MVC) spontaneously undergo angiogenesis in static conditions in vitro but form a new microcirculation only when implanted in vivo. We have designed a bioreactor, the dynamic in vitro perfusion (DIP) chamber, to culture MVCs in vitro with perfusion. By altering bioreactor circulation, microvessel fragments in the DIP chamber either maintained stable, nonsprouting, patent vessel morphologies or sprouted endothelial neovessels that extended out into the surrounding collagen matrix (i.e., angiogenesis), yielding networks of neovessels within the MVC. Neovessels formed in regions of the construct predicted by simulation models to have the steepest gradients in oxygen levels and expressed hypoxia inducible factor-1α. By altering circulation conditions in the DIP chamber, we can control, possibly by modulating hypoxic stress, prevascularizing activity in vitro.
In addition to its role in reproduction, estradiol-17β is critical to the regulation of energy balance and body weight. Estrogen receptor α–null (Erα–/–) mutant mice develop an obese state characterized by decreased energy expenditure, decreased locomotion, increased adiposity, altered glucose homeostasis, and hyperleptinemia. Such features are reminiscent of the propensity of postmenopausal women to develop obesity and type 2 diabetes. The mechanisms by which ERα signaling maintains normal energy balance, however, have remained unclear. Here we used knockin mice that express mutant ERα that can only signal through the noncanonical pathway to assess the role of nonclassical ERα signaling in energy homeostasis. In these mice, we found that nonclassical ERα signaling restored metabolic parameters dysregulated in Erα–/– mutant mice to normal or near-normal values. The rescue of body weight and metabolic function by nonclassical ERα signaling was mediated by normalization of energy expenditure, including voluntary locomotor activity. These findings indicate that nonclassical ERα signaling mediates major effects of estradiol-17β on energy balance, raising the possibility that selective ERα agonists may be developed to reduce the risks of obesity and metabolic disturbances in postmenopausal women.
The function of the glenohumeral capsule has typically been evaluated by isolating several discrete, ligamentous regions during experimental and computational investigations. However, recent data suggests that the regions of the glenohumeral capsule have significant interactions and function multiaxially. Therefore, examining the function of the inferior glenohumeral ligament as a discrete structure may not be appropriate. The objective of this work was to validate the predicted strain distribution and deformed shape of the inferior glenohumeral ligament using experimental data for two subject-specific finite element models: (1) a continuous model including all capsular regions, and (2) a discrete model including only the inferior glenohumeral ligament. The distribution of maximum principal strain and deformed shape of the glenohumeral capsule was determined for a cadaveric shoulder in a joint position frequently associated with dislocation (60° of glenohumeral abduction, 52° of external rotation, and a 25 N anterior load applied to the humerus). The experimental kinematics were then applied to the two finite element models constructed from the geometry and material properties from the same cadaveric shoulder and the predicted strain distributions and deformed shapes were determined. For the continuous model, the average difference between predicted strains and experimental strains was less than 5%. The predicted deformed shape was also similar to experimental data, with the anterior band of the inferior glenohumeral ligament clearly wrapped around the humeral head. In contrast, large differences existed between the strains predicted by the discrete model when compared to the experimental strains for this joint position (average difference from experimental data was 20%). In addition, the predicted deformed shape of the inferior glenohumeral ligament did not wrap around the humeral head. These differences may be attributed to neglecting the complex interactions between the anterior band of the inferior glenohumeral ligament with the neighboring capsular regions. Thus, the glenohumeral capsule should not be evaluated as several discrete structures. Rather, it should be evaluated as a single sheet of fibrous tissue.
Shoulder; Strain; Kinematics
Mortality in HIV-positive persons is increasingly due to non-HIV–related medical comorbidities. There are limited data on the prevalence and patient awareness of these comorbid conditions. Two hundred subjects at an urban HIV clinic were interviewed in 2005 to assess their awareness of 15 non-HIV–related medical comorbidities, defined as medical problems that are neither AIDS-defining by standard definitions, nor a direct effect of immune deficiency. Medical charts were subsequently reviewed to establish prevalence and concordance between self-report and chart documentation. Eighty-four percent of subjects self-reported at least 1 of 15 medical comorbidities and 92% had at least 1 condition chart-documented. The top 5 chart-documented conditions were hepatitis C (51.5%), pulmonary disease (28.5%), high blood pressure (27%), high cholesterol (24.5%), and obesity (22.5%). In multivariate analysis, higher number of non-HIV–related medical comorbidities was associated with older age, female gender, and intravenous drug use as route of HIV transmission. Across self-reported non-HIV–related medical comorbidities, the absolute concordance rate ranged from 67% to 96%, the sensitivity ranged from 0% to 79%; the positive predictive value ranged from 0% to 100%. While the vast majority of largely urban minority HIV-positive subjects were diagnosed with non-HIV–related medical comorbidities, there is significant room for improvement in patient awareness. In order to help patients optimally access and adhere to medication and medical care for these non-HIV–related medical comorbidities, interventions and educational campaigns to improve patient awareness that take cultural background, literacy, and educational level into account should be developed, implemented, and evaluated.
To determine expert clinical practice in the management of psychiatric status of HIV/HCV-co-infected patients initiating pegylated interferon/ribavirin for the treatment of Hepatitis C.
Two hundred and thirty-six expert providers were identified and invited by email to complete an online anonymous survey.
Ninety-two providers (39%) completed the survey; 24 (26%) of whom are psychiatrists. More than one-third of providers indicate that they use or offer the option of antidepressant use prophylactically in HIV-positive patients with no past or current depression beginning HCV treatment and more than three-quarters do so in patients with a history of depression, but no current symptoms of depression. The most experienced non-psychiatrist providers were more likely to use antidepressants prior to the start of treatment in HIV-co-infected patients as compared to in HCV mono-infected patients. There is consensus among providers to leave psychiatric medication unchanged in patients currently treated for unipolar depression.
Many expert providers prescribe antidepressants to HIV/HCV-co-infected patients initiating Hepatitis C treatment in the absence of symptoms of depression, despite the lack of data supporting this approach in this population. Research is needed to provide an evidence base to guide the optimal psychiatric management of HIV/HCV-co-infected patients beginning Hepatitis C treatment.
HIV/HCV coinfection; depression; interferon; ribavirin
The topics of verification and validation (V&V) have increasingly been discussed in the field of computational biomechanics, and many recent articles have applied these concepts in an attempt to build credibility for models of complex biological systems. V&V are evolving techniques that, if used improperly, can lead to false conclusions about a system under study. In basic science these erroneous conclusions may lead to failure of a subsequent hypothesis, but they can have more profound effects if the model is designed to predict patient outcomes. While several authors have reviewed V&V as they pertain to traditional solid and fluid mechanics, it is the intent of this manuscript to present them in the context of computational biomechanics. Specifically, the task of model validation will be discussed with a focus on current techniques. It is hoped that this review will encourage investigators to engage and adopt the V&V process in an effort to increase peer acceptance of computational biomechanics models.
biomechanics; computation; validation; verification; modeling
Prior research on adherence to Hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence.
To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings.
180 patients on treatment for Hepatitis C (23% co-infected with HIV) completed a cross-sectional survey at the site of their Hepatitis C care.
Seven percent of patients reported missing at least one injection of pegylated interferon in the last four weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load.
Self-reported dose nonadherence to Hepatitis C treatment occurs frequently. Further studies of dose nonadherence (assessed by method other than self-report) and its relationship to HCV virologic outcome are warranted.
Adherence; HCV; HIV; co-infection; interferon; ribavirin
To prospectively assess in a phantom the reconstruction errors and detection limits of cartilage thickness measurements from MDCT arthrography as a function of contrast agent concentration, imaging plane, spatial resolution, joint space and tube current, using known measurements as the reference standard.
MATERIALS AND METHODS
A phantom with nine chambers was manufactured. Each chamber had a nylon cylinder encased by sleeves of aluminum and polycarbonate to simulate trabecular bone, cortical bone, and cartilage. Variations in simulated cartilage thickness and joint space were assessed. The phantom was scanned with and without contrast agent on three separate days, with chamber axes both perpendicular and parallel to the scanner axis. Images were reconstructed at intervals of both 1.0 and 0.5 mm. Contrast agent concentration and tube current were varied. Simulated cartilage thickness was determined from image segmentation. Root mean squared and mean residual errors were used to characterize the measurements. CT scanner and image segmentation reproducibility were determined.
Simulated cartilage was reconstructed with < 10% error for thicknesses >1.0 mm when no contrast agent or a low concentration of contrast agent (25%) was used. Errors grew as concentration of contrast agent increased. Decreasing the simulated joint space to 0.5 mm caused slight increases in error; below 0.5 mm errors grew substantially. Measurements from anisotropic image data had errors greater than those for isotropic data. Altering tube current did not affect reconstruction errors.
Our study establishes lower bounds and repeatability of simulated cartilage thickness measurement using MDCT arthrography, and provides data pertinent to choosing contrast agent concentration, joint spacing, scanning plane, and spatial resolution to reduce reconstruction errors.
CT arthrography; phantom; reconstruction error; cartilage; thickness
The objective of this study was to validate a deformable image registration technique, termed Hyperelastic Warping, for left ventricular strain measurement during systole using cine-gated, nontagged MR images with strains measured from tagged MRI. The technique combines deformation from high resolution, non-tagged MR image data with a detailed computational model, including estimated myocardial material properties, fiber direction, and active fiber contraction, to provide a comprehensive description of myocardial contractile function. A normal volunteer (male, age 30) with no history of cardiac pathology was imaged with a 1.5 T Siemens Avanto clinical scanner using a TrueFISP imaging sequence and a 32-channel cardiac coil. Both tagged and non-tagged cine MR images were obtained. The Hyperelastic Warping solution was evolved using a series of non-tagged images in ten intermediate phases from end-diastole to end-systole. The solution may be considered as ten separate warping problems with multiple templates and targets. At each stage, an active contraction was initially applied to a finite element model, and then image-based warping penalty forces were utilized to generate the final registration. Warping results for circumferential strain (R2 = 0.75) and radial strain (R2 = 0.78) were strongly correlated with results obtained from tagged MR images analyzed with a Harmonic Phase (HARP) algorithm. Results for fiber stretch, LV twist, and transmural strain distributions were in good agreement with experimental values in the literature. In conclusion, Hyperelastic Warping provides a unique alternative for quantifying regional LV deformation during systole without the need for tags.
Strain; Left ventricle; Systole; Deformable image registration; Soft tissue mechanics; Finite element; Magnetic resonance imaging