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Control-Based Continuation (CBC) is a general and systematic method to carry out the bifurcation analysis of physical experiments. CBC does not rely on a mathematical model and thus overcomes the uncertainty introduced when identifying bifurcation curves indirectly through modeling and parameter estimation. We demonstrate, in silico , CBC applicability to biochemical processes by tracking the equilibrium curve of a toggle switch, which includes additive process noise and exhibits bistability. We compare the results obtained when CBC uses a model-free and model-based control strategy and show that both can track stable and unstable solutions, revealing bistability. We then demonstrate CBC in conditions more representative of an in vivo experiment using an agent-based simulator describing cell growth and division, cell-to-cell variability, spatial distribution, and diffusion of chemicals. We further show how the identified curves can be used for parameter estimation and discuss how CBC can significantly accelerate the prototyping of synthetic gene regulatory networks.

Nonlinear normal modes (NNMs) are widely used as a tool for developing mathematical models of nonlinear structures and understanding their dynamics. NNMs can be identified experimentally through a phase quadrature condition between the system response and the applied excitation. This paper demonstrates that this commonly used quadrature condition can give results that are significantly different from the true NNM, in particular, when the excitation applied to the system is limited to one input force, as is frequently used in practice. The system studied is a clamped-clamped cross-beam with two closely spaced modes. This paper shows that the regions where the quadrature condition is (in)accurate can be qualitatively captured by analysing transfer of energy between the modes of the system, leading to a discussion of the appropriate number of input forces and their locations across the structure., Competing Interests: We declare we have no competing interests.

Introduction: Government-funded quality improvement projects aimed to reduce the high psychotropic medication use in Belgian long-term care settings., Design: A pilot project (2013-2014) with a pre-post and follow-up intervention design., Methods: Two nursing homes received three educational courses. In the intervention nursing home (INH) additionally, a transition towards person-centred care through professional support was applied. Drug use was recorded at baseline, after 10 months (post) and after 22 months (follow-up), and coded into the Anatomical Therapeutic Chemical classification., Results: At baseline, the INH residents' (n = 118) mean age at baseline was 82 years, with 71% females. The control nursing home residents' (CNH, n = 275) mean age was 82.7 years, with 75% females. At baseline, mean drug use was 9 (range 1-21) and 8 (range 0-20), predominantly with a high proportion of psychotropic drug users of 73 and 65%, in INH and CNH respectively. At the time of post-measurement, only the proportion of hypno-sedative users decreased significantly in the INH (by 13%, p = 0.048). No significant changes were found in the CNH. At time of the follow-up, the proportion of hypno-sedative (51% vs. 31%; p = 0.005) and antidepressant users (42% vs. 25%, p = 0.007) decreased significantly in the INH. The decrease of antipsychotic drug users was less distinct. In the CNH, the proportion of hypno-sedative, antidepressant and overall psychotropic drug users did not change significantly., Conclusion: This quality improvement initiative led to a significant decrease in the use of psychotropic drugs in the INH, even after 1-year follow-up. Education only had a limited effect.

Background: Achieving accurate alignment in total knee arthroplasty (TKA) remains a concern. Patient-specific instrumentation (PSI) produced using preoperative 3D models was developed to offer surgeons a simplified, reliable, efficient and customised TKA procedure., Methods: In this prospective study, 60 patients underwent TKA with conventional instrumentation and 71 patients were operated on using PSI. The primary endpoint was surgical time. Secondary endpoints included operating room (OR) time, the number of instrument trays used and postoperative radiographic limb alignment., Results: Compared to conventional instrumentation, PSI significantly reduced total surgical time by 8.9 ± 3.3 min (p=0.038), OR time by 8.6 ± 4.2 min (p=0.043), and the number of instrument trays by six trays (p<0.001). Mechanical axis malalignment of the lower limb of >3° was observed in 13% of PSI patients versus 29% with conventional instrumentation (p=0.043). PSI predicted the size of the femoral and tibial components actually used in 85.9% and 78.9% of cases, respectively., Conclusion: PSI improves alignment, surgical and OR time, reduces the number of instruments trays used compared to conventional instrumentation in patients undergoing TKA and results in fewer outliers in overall mechanical alignment in the coronal plane., Level of Evidence Ii: Prospective comparative therapeutic study., (Copyright © 2014 Elsevier B.V. All rights reserved.)

To establish the value of quantitative radionuclide bone scanning after total knee replacement, 21 patients were scheduled for examination. Eight patients were scanned more than 1 year after surgery (group 1), and 13 within the first postsurgical year (group 2). Ratios were calculated for three regions of interest. The ratio was defined as the counts per pixel for each region of interest, normalized by dividing them by the counts per pixel of the ipsilateral femoral shaft. There was no significant difference in uptake between control subjects and patients in group 2, indicating that the test was not reliable within this time period. No statistical difference was found between the uptake scores in groups 1 and 2, demonstrating that an uninterpretable period of 1 year is perhaps too short. Using a ratio of more than three, seen more than 1 year after surgery as pathologic, a sensitivity of 100%, a specificity of 33%, and an accuracy of 75% was found. Quantitative bone scanning is a very sensitive test for detecting complications, but it is nonspecific in diagnosing loosening of total knee arthroplasties. The value of quantitative scanning presumably lies in the follow-up of patients as an objective method for the evaluation of sequential scanning. Nevertheless, radionuclide data need to be interpreted in correlation with clinical and radiologic findings.

Osteoid osteoma is a benign tumor frequently situated around the knee. It should therefore be considered as a possible cause of atraumatic knee pain in young adults. The mean interval from onset of symptoms to diagnosis is 14 months. Clinical symptoms are the most reliable diagnostic factors. Block resection is the treatment of choice. A retrospective study of 10 patients is presented.

In both radiological and orthopedic journals the value of MRI for diagnosing internal derangement of the knee has been assessed recently. However, results vary widely and no study reports on the differentiation among types of ACL tears. As far as meniscal pathology is concerned, attention has been drawn by Reicher et al. (11) and Glashow et al. (5) upon the false positive tears of the posterior horn of the medial meniscus. Where most authors consider signal inversion in the posterior horn of the meniscus as a normal finding in children--due to the higher water content--the same fact in adults can be interpreted as a false positive image or a missed tear at arthroscopy (5).

A 1 year prospective study was done to develop an accident-prone and overuse-prone profile of young athletes. A group of 185 freshman physical education students (118 males; 67 females of the same age (18.3 +/- 0.5 years) trained under the same conditions and were exposed to similar extrinsic risk factors. Using a descriptive statistical technique, an analysis of correspondence, the complex interrelation between the criterium variables (acute injuries and overuse injuries) and the predictor variables (intrinsic risk factors; physical characteristics--anthropometric data, physical fitness parameters, flexibility aspects and malalignment of the lower extremities; and psychological factors--16 personality traits) was estimated for males and females separately. Although dynamic strength seems to be an important risk factor in acute injuries, sports accidents must be seen in relation to psychological factors. However, the overuse-prone profile is mainly based on physical traits: a combination of muscle weakness, ligamentous laxity, and muscle tightness predisposes to stress injuries. In addition, these overuse effects are intensified by large body weight and length, a high explosive strength, and malalignment of the lower limbs. Nevertheless, it has to be kept in mind that psychosomatic factors play a role in how one experiences these overuse phenomena.