Inverse kinematic total knee arthroplasty using conventional instrumentation restores constitutional coronal alignment.

PURPOSE: Restricted inverse kinematic alignment (iKA) is a contemporary alignment strategy for total knee arthroplasty (TKA), commonly performed with robotic assistance. While superior clinical results are reported for kinematic-type alignment strategies, registry data indicate no survivorship benefit for navigation or robotic assistance. This study aimed to determine the efficacy of an instrumented, restricted iKA technique for achieving patient-specific alignment. METHODS: Seventy-nine patients undergoing 84 TKAs (five bilateral procedures) using an iKA technique were included for preoperative and postoperative lower limb alignment analysis. The mean age was 66.5 (range: 43-82) with 33 male and 51 female patients. Artificial intelligence was employed for radiographic measurements. Alignment profiles were classified using the Coronal Plane Alignment of the Knee (CPAK) system. Preoperative and postoperative alignment profiles were compared with subanalyses for preoperative valgus, neutral and varus profiles. RESULTS: The mean joint-line convergence angle (JLCA) reduced from 2.5° to -0.1° postoperatively. The mean lateral distal femoral angle (LDFA) remained unchanged postoperatively, while the mean medial proximal tibial angle (MPTA) increased by 2.5° (p = 0.001). By preservation of the LDFA and restoration of the MPTA, the mean hip knee ankle angle (HKA) moved through 3.5° varus to 1.2° valgus. The CPAK system was used to visually depict changes in alignment profiles for preoperative valgus, neutral and varus knees; with 63% of patients observing an interval change in classification. CONCLUSION: Encouraged by the latest evidence supporting both conventional instrumentation and kinematic-type TKA strategies, this study describes how a restricted, conventionally instrumented iKA technique may be utilised to restore constitutional lower limb alignment. LEVEL OF EVIDENCE: Level III.

Modeling mechanical control of spindle orientation of intestinal crypt stem cells.

Tissue development requires a control over the sequence of symmetric and asymmetric stem cell divisions to obtain the specific numbers of differentiated cells populating the tissue and stem cells residing in the niche. A good experimental model to study this process is the mouse intestinal crypt development, where it has been shown that stem cells follow an optimal strategy in which asymmetric division occurs only after all symmetric divisions have taken place to reach a fixed number of cells in the niche in the shortest time. Here we introduce a model of stem cell division that is able to explain the experimentally observed stem cell population dynamics by the effect of mechanical forces acting on the spindle. We also observe that the mechanically induced strategy for development is sub-optimal and crucially depends on the stiffness of the spindle. These findings highlight the crucial importance of mechanical forces for the development and maintenance of the intestinal crypt.

Conformational mechanism for the stability of microtubule-kinetochore attachments.

Regulating the stability of microtubule (MT)-kinetochore attachments is fundamental to avoiding mitotic errors and ensuring proper chromosome segregation during cell division. Although biochemical factors involved in this process have been identified, their mechanics still need to be better understood. Here we introduce and simulate a mechanical model of MT-kinetochore interactions in which the stability of the attachment is ruled by the geometrical conformations of curling MT-protofilaments entangled in kinetochore fibrils. The model allows us to reproduce, with good accuracy, in vitro experimental measurements of the detachment times of yeast kinetochores from MTs under external pulling forces. Numerical simulations suggest that geometrical features of MT-protofilaments may play an important role in the switch between stable and unstable attachments.

Automated Knee Osteoarthritis Assessment Increases Physicians' Agreement Rate and Accuracy: Data from the Osteoarthritis Initiative.

Objective. To assess the impact of a computerized system on physicians' accuracy and agreement rate, as compared with unaided diagnosis. Methods. A set of 124 unilateral knee radiographs from the Osteoarthritis Initiative (OAI) study were analyzed by a computerized method with regard to Kellgren-Lawrence (KL) grade, as well as joint space narrowing, osteophytes, and sclerosis Osteoarthritis Research Society International (OARSI) grades. Physicians scored all images, with regard to osteophytes, sclerosis, joint space narrowing OARSI grades and KL grade, in 2 modalities: through a plain radiograph (unaided) and a radiograph presented together with the report from the computer assisted detection system (aided). Intraclass correlation between the physicians was calculated for both modalities. Furthermore, physicians' performance was compared with the grading of the OAI study, and accuracy, sensitivity, and specificity were calculated in both modalities for each of the scored features. Results. Agreement rates for KL grade, sclerosis, and osteophyte OARSI grades, were statistically increased in the aided versus the unaided modality. Readings for joint space narrowing OARSI grade did not show a statistically difference between the 2 modalities. Readers' accuracy and specificity for KL grade >0, KL >1, sclerosis OARSI grade >0, and osteophyte OARSI grade >0 was significantly increased in the aided modality. Reader sensitivity was high in both modalities. Conclusions. These results show that the use of an automated knee OA software increases consistency between physicians when grading radiographic features of OA. The use of the software also increased accuracy measures as compared with the OAI study, mostly through increases in specificity.

Deformation and fracture of echinoderm collagen networks.

Collagen networks provide the main structural component of most tissues and represent an important ingredient for bio-mimetic materials for bio-medical applications. Here we study the mechanical properties of stiff collagen networks derived from three different echinoderms and show that they exhibit non-linear stiffening followed by brittle fracture. The disordered nature of the network leads to strong sample-to-sample fluctuations in elasticity and fracture strength. We perform numerical simulations of a three dimensional model for the deformation of a cross-linked elastic fibril network which is able to reproduce the macroscopic features of the experimental results and provide insights into the internal mechanics of stiff collagen networks. Our numerical model provides an avenue for the design of collagen membranes with tunable mechanical properties.

Role of the Number of Microtubules in Chromosome Segregation during Cell Division.

Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compares well with early observations in mammalian cell spindles. Our results shed new light on the origin of several pathological conditions related to chromosomal instability.

Navigation Strategies of Motor Proteins on Decorated Tracks.

Motor proteins display widely different stepping patterns as they move on microtubule tracks, from the deterministic linear or helical motion performed by the protein kinesin to the uncoordinated random steps made by dynein. How these different strategies produce an efficient navigation system needed to ensure correct cellular functioning is still unclear. Here, we show by numerical simulations that deterministic and random motor steps yield different outcomes when random obstacles decorate the microtubule tracks: kinesin moves faster on clean tracks but its motion is strongly hindered on decorated tracks, while dynein is slower on clean tracks but more efficient in avoiding obstacles. Further simulations indicate that dynein's advantage on decorated tracks is due to its ability to step backwards. Our results explain how different navigation strategies are employed by the cell to optimize motor driven cargo transport.

Wrinkle motifs in thin films.

On length scales from nanometres to metres, partial adhesion of thin films with substrates generates a fascinating variety of patterns, such as 'telephone cord' buckles, wrinkles, and labyrinth domains. Although these patterns are part of everyday experience and are important in industry, they are not completely understood. Here, we report simulation studies of a previously-overlooked phenomenon in which pairs of wrinkles form avoiding pairs, focusing on the case of graphene over patterned substrates. By nucleating and growing wrinkles in a controlled way, we characterize how their morphology is determined by stress fields in the sheet and friction with the substrate. Our simulations uncover the generic behaviour of avoiding wrinkle pairs that should be valid at all scales.

Accelerated stochastic sampling of discrete statistical systems.

We propose a method to reduce the relaxation time toward equilibrium in stochastic sampling of complex energy landscapes in statistical systems with discrete degrees of freedom by generalizing the platform previously developed for continuous systems. The method starts from a master equation, in contrast to the Fokker-Planck equation for the continuous case. The master equation is transformed into an imaginary-time Schrödinger equation. The Hamiltonian of the Schrödinger equation is modified by adding a projector to its known ground state. We show how this transformation decreases the relaxation time and propose a way to use it to accelerate simulated annealing for optimization problems. We implement our method in a simplified kinetic Monte Carlo scheme and show acceleration by one order of magnitude in simulated annealing of the symmetric traveling salesman problem. Comparisons of simulated annealing are made with the exchange Monte Carlo algorithm for the three-dimensional Ising spin glass. Our implementation can be seen as a step toward accelerating the stochastic sampling of generic systems with complex landscapes and long equilibration times.