Investigation of the dependence of joint contact forces on musculotendon parameters using a codified workflow for image-based modelling

The generation of subject-specific musculoskeletal models of the lower limb has become a feasible taskthanks to improvements in medical imaging technology and musculoskeletal modelling software.Nevertheless, clinical use of these models in paediatric applications is still limited for what concernsthe estimation of muscle and joint contact forces. Aiming to improve the current state of the art, amethodology to generate highly personalized subject-specific musculoskeletal models of the lower limbbased on magnetic resonance imaging (MRI) scans was codified as a step-by-step procedure and appliedto data from eight juvenile individuals. The generated musculoskeletal models were used to simulate 107gait trials using stereophotogrammetric and force platform data as input. To ensure completeness of themodelling procedure, muscles’ architecture needs to be estimated. Four methods to estimate muscles’maximum isometric force and two methods to estimate musculotendon parameters (optimal fiber lengthand tendon slack length) were assessed and compared, in order to quantify their influence on the models’output. Reported results represent the first comprehensive subject-specific model-based characterizationof juvenile gait biomechanics, including profiles of joint kinematics and kinetics, muscle forces and jointcontact forces. Our findings suggest that, when musculotendon parameters were linearly scaled from areference model and the muscle force-length-velocity relationship was accounted for in the simulations,realistic knee contact forces could be estimated and these forces were not sensitive the method used tocompute muscle maximum isometric force

Chancengerechtigkeit durch Bildung – Chancengerechtigkeit in der Bildung (Auszug)

Der hier mit freundlicher Genehmigung des AWO Bundesverbands abgedruckte Text ist ein Auszug aus der Broschüre: Arbeiterwohlfahrt Bundesverband (Hrsg.): Standpunkte 2006. Chancengerechtigkeit durch Bildung – Chancengerechtigkeit in der Bildung, Bonn 2006. Unser Bildungssystem für die Kinder im Alter von 6 bis 16 Jahren wird den Herausforderungen der Zukunft nicht gerecht. Ein Umsteuern ist dringend notwendig, da ohne Bildung der Wandel in die Wissensgesellschaft nicht zu bewältigen ist. Bildung, Qualifikation und Kompetenzen und das Erlernen von Diskurs- und Konfliktfähigkeit entscheiden über die beruflichen und gesellschaftlichen Chancen eines jeden Menschen und davon abhängig über seine Zukunftschancen. Bildung bedeutet Entwicklung der Persönlichkeit, der Identität. Bildung bedeutet aber auch, die gemeinschaftsfähige Persönlichkeit zu gestalten. Und somit bekommt Bildung gerade in der Lebensphase der 6- bis 16-Jährigen über die eher traditionelle Dimension hinaus auch einen emanzipatorischen Charakter. Wenn Bildung also für den Einzelnen diese entscheidende Rolle spielt, dann bekommt die öffentliche Verantwortung für dieses Bildungswesen eine ganz zentrale Bedeutung. (DIPF/Orig.

Linking joint impairment and gait biomechanics in patients with Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis (JIA) is a paediatric musculoskeletal disease of unknown aetiology, leading to walking alterations when the lower-limb joints are involved. Diagnosis of JIA is mostly clinical. Imaging can quantify impairments associated to inflammation and joint damage. However, treatment planning could be better supported using dynamic information, such as joint contact forces (JCFs). To this purpose, we used a musculoskeletal model to predict JCFs and investigate how JCFs varied as a result of joint impairment in eighteen children with JIA. Gait analysis data and magnetic resonance images (MRI) were used to develop patient-specific lower-limb musculoskeletal models, which were evaluated for operator-dependent variability (< 3.6°, 0.05 N kg−1 and 0.5 BW for joint angles, moments, and JCFs, respectively). Gait alterations and JCF patterns showed high between-subjects variability reflecting the pathology heterogeneity in the cohort. Higher joint impairment, assessed with MRI-based evaluation, was weakly associated to overall joint overloading. A stronger correlation was observed between impairment of one limb and overload of the contralateral limb, suggesting risky compensatory strategies being adopted, especially at the knee level. This suggests that knee overloading during gait might be a good predictor of disease progression and gait biomechanics should be used to inform treatment planning

Cochlear implant programming: a global survey on the state of the art

The programming of CIs is essential for good performance. However, no Good Clinical Practice guidelines exist. This paper reports on the results of an inventory of the current practice worldwide. A questionnaire was distributed to 47 CI centers. They follow 47600 recipients in 17 countries and 5 continents. The results were discussed during a debate. Sixty-two percent of the results were verified through individual interviews during the following months. Most centers (72%) participated in a cross-sectional study logging 5 consecutive fitting sessions in 5 different recipients. Data indicate that general practice starts with a single switch-on session, followed by three monthly sessions, three quarterly sessions, and then annual sessions, all containing one hour of programming and testing. The main focus lies on setting maximum and, to a lesser extent, minimum current levels per electrode. These levels are often determined on a few electrodes and then extrapolated. They are mainly based on subjective loudness perception by the CI user and, to a lesser extent, on pure tone and speech audiometry. Objective measures play a small role as indication of the global MAP profile. Other MAP parameters are rarely modified. Measurable targets are only defined for pure tone audiometry. Huge variation exists between centers on all aspects of the fitting practice

Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer

Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC

A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important