Minimization of Intra-Operative Shaping of Orthopaedic Fixation Plates: A Population-Based Design

In this paper we present a new population-based method for the design of bone fixation plates. Standard pre-contoured plates are designed based on the mean shape of a certain population. We propose a computational process to design implants while reducing the amount of required intra-operative shaping, thus reducing the mechanical stresses applied to the plate. A bending and torsion model was used to measure and minimize the necessary intra-operative deformation. The method was applied and validated on a population of 200 femurs that was further augmented with a statistical shape model. The obtained results showed substantial reduction in the bending and torsion needed to shape the new design into any bone in the population when compared to the standard mean-based plates.

Population-Based Design of Mandibular Plates Based on Bone Quality and Morphology

In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method enhances the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. Using computational anatomy techniques, the method automatically derives, from a set of computed tomography images, the mandibular angle and the bone thickness and intensity values at the path of every screw. An optimisation strategy is then used to optimise the two parameters of plate angle and screw position. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate. A statistically highly significant improvement was observed. Our experiments allowed us to conclude that an angle of 126° and a screw separation of 8mm is a more suitable design than the standard 120° and 9mm.

Population-based design of mandibular fixation plates with bone quality and morphology considerations

In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method may enhance the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The computational method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. The method automatically derives the mandibular angle and the bone thickness and intensity values at the path of every screw from a set of computed tomography images. An optimization strategy is then used to optimize the two parameters of plate angle and screw position. The method was applied to two populations of different genders. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate (MODUS(®) TriLock(®) 2.0/2.3/2.5, Medartis AG, Basel, Switzerland). The proposed designs resulted in a statistically significant improvement in the available bone thickness when compared to the standard plate. There is a higher probability that the proposed implants cover areas of thicker cortical bone without compromising the bone mineral density around the screws. The obtained results allowed us to conclude that an angle and screw separation of 129° and 9 mm for females and 121° and 10 mm for males are more suitable designs than the commercially available 120° and 9 mm.

The Law of the WTO and the Communications Law of the EC : On a Path of Harmony or Discord?

This paper presents an overview of the law of the World Trade Organization (WTO) relevant to telecommunications services and correlates this body of law with the current regulatory framework for electronic communications networks and services in the European Community. The latter has been adapted to meet the challenges of technological and market developments in communications, epitomized by the processes of digitization, enhanced transport networks and convergence. The novel solutions embodied in the EC electronic communications regime, notably, a new design of the Significant Market Power mechanism, a projected withdrawal of sector specific regulation and an affirmation of the principle of technological neutrality, pose interesting questions as to the conformity of this reformed EC communications law with the WTO rules on telecommunications services and the obligations of the European Communities and their Member States. Looking beyond the WTO legal compatibility test, essential questions regarding the need for evolution of the WTO telecommunications rules are raised. The present paper contributes to the ongoing debate in that context in light of the EC experience.

Searching the hearts of graphene-like molecules for simplicity, sensitivity and logic

If quantum interference patterns in the hearts of polycyclic aromatic hydrocarbons (PAHs) could be isolated and manipulated, then a significant step towards realizing the potential of single-molecule electronics would be achieved. Here we demonstrate experimentally and theoretically that a simple, parameter-free, analytic theory of interference patterns evaluated at the mid-point of the HOMO-LUMO gap (referred to as M-functions) correctly predicts conductance ratios of molecules with pyrene, naphthalene, anthracene, anthanthrene or azulene hearts. M-functions provide new design strategies for identifying molecules with phase-coherent logic functions and enhancing the sensitivity of molecular-scale interferometers.

Towards Batteryless Cardiac Implantable Electronic Devices – The Swiss Way

Energy harvesting devices are widely discussed as an alternative power source for todays active implantable medical devices. Repeated battery replacement procedures can be avoided by extending the implants life span, which is the goal of energy harvesting concepts. This reduces the risk of complications for the patient and may even reduce device size. The continuous and powerful contractions of a human heart ideally qualify as a battery substitute. In particular, devices in close proximity to the heart such as pacemakers, defibrillators or bio signal (ECG) recorders would benefit from this alternative energy source. The clockwork of an automatic wristwatch was used to transform the hearts kinetic energy into electrical energy. In order to qualify as a continuous energy supply for the consuming device, the mechanism needs to demonstrate its harvesting capability under various conditions. Several in-vivo recorded heart motions were used as input of a mathematical model to optimize the clockworks original conversion efficiency with respect to myocardial contractions. The resulting design was implemented and tested during in-vitro and in-vivo experiments, which demonstrated the superior sensitivity of the new design for all tested heart motions.

Synthesis and biological activity of new functionalized epothilones for prodrug design and tumor targeting

Epothilones are potent antiproliferative agents, which have served as successful lead structures for anticancer drug discovery. However, their therapeutic efficacy would benefit greatly from an increase in their selectivity for tumor cells, which may be achieved through conjugation with a tumor-targeting moiety. Three novel epothilone analogs bearing variously functionalized benzimidazole side chains were synthesized using a strategy based on palladium-mediated coupling and macrolactonization. The synthesis of these compounds is described and their in vitro biological activity is discussed with respect to their interactions with the tubulin/microtubule system and the inhibition of human cancer cell proliferation. The additional functional groups may be used to synthesize conjugates of epothilone derivatives with a variety of tumor-targeting moieties.

Design and construction of a new Drosophila species, D.synthetica, by synthetic regulatory evolution

Here, I merge the principles of synthetic biology1,2 and regulatory evolution3-11 to create a new species12-15 with a minimal set of known elements. Using preexisting transgenes and recessive mutations of Drosophila melanogaster, a transgenic population arises with small eyes and a different venation pattern that fulfills the criteria of a new species according to Mayr's "Biological Species Concept"7,10. The genetic circuit entails the loss of a non-essential transcription factor and the introduction of cryptic enhancers. Subsequent activation of those enhancers causes hybrid lethality. The transition from "transgenic organisms" towards "synthetic species", such as Drosophila synthetica, constitutes a safety mechanism to avoid hybridization with wild type populations and preserve natural biodiversity16-18. Drosophila synthetica is the first transgenic organism that cannot hybridize with the original wild type population but remains fertile when crossed with other transgenic animals.

The Design of International Trade Agreements: Introducing a New Dataset

Preferential trade agreements (PTAs) have been proliferating for the last twenty years. A large literature has studied various aspects of this phenomenon. Until recently, however, many large-N studies have paid only scant attention to variation across PTAs in terms of content and design. Our contribution to this literature is a new dataset on the design of trade agreements that is the most comprehensive in terms of both variables coded and agreements covered. We illustrate the dataset’s usefulness in re-visiting the questions if and to what extent PTAs impact trade flows. The analysis shows that on average PTAs increase trade flows, but that this effect is largely driven by deep agreements. In addition, we provide evidence that provisions that tackle behind-the-border regulation matter for trade flows. The dataset’s contribution is not limited to the PTA literature, however. Broader debates on topics such as institutional design and the legalization of international relations will also benefit from the novel data.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.