Development of a dry, stable and inhalable acyl–homoserine–lactone–acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections

In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl–homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20 °C and 55 °C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55 °C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of ∼1.8 μm implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation

Debating the Desirability of New Biomedical Technologies: Lessons from the Introduction of Breast Cancer Screening in the Netherlands

Health technology assessment (HTA) was developed in the 1970s and 1980s to facilitate decision making on the desirability of new biomedical technologies. Since then, many of the standard tools and methods of HTA have been criticized for their implicit normativity. At the same time research into the character of technology in practice has motivated philosophers, sociologists and anthropologists to criticize the traditional view of technology as a neutral instrument designed to perform a specific function. Such research suggests that the tools and methods of more traditional forms of HTA are often inspired by an ‘instrumentalist’ conception of technology that does not fit the way technology actually works. This paper explores this hypothesis for a specific case: the assessments and deliberations leading to the introduction of breast cancer screening in the Netherlands. After reconstructing this history of HTA ‘in the making’ the stepwise model of HTA that emerged during the process is discussed. This model was rooted indeed in an instrumentalist conception of technology. However, a more detailed reconstruction of several episodes from this history reveals how the actors already experienced the inadequacy of some of the instrumentalist presuppositions. The historical case thus shows how an instrumentalist conception of technology may result in implicit normative effects. The paper concludes that an instrumentalist view of technology is not a good starting point for HTA and briefly suggests how the fit between HTA methods and the actual character of technology in practice might be improved

Characterizing the emergence of a technological field: Expectations, agendas and networks in Lab-on-a-chip technologies

International audienc

Fracture of Metal Foams: In-situ Testing and Numerical Modeling

This paper is on a combined experimental/modeling study on the tensile fracture of open-cell foams. In-situ tensile tests show that individual struts can fail in a brittle or ductile mode, presumably depending on the presence of casting defects. In-situ single strut tests were performed, enabling observation of deformation and fracture behavior and, in addition, serving as calibration for the proposed single-strut model. The single strut model consists of beam elements to account for elasticity and plasticity, and of special-purpose fracture elements to account for failure. The model is demonstrated for a characteristic loading configuration, combining stretching and bending.

Technical Aspects and Validation of a New Biofeedback System for Measuring Lower Limb Loading in the Dynamic Situation

Background: A variety of techniques for measuring lower limb loading exists, each with their own limitations. A new ambulatory biofeedback system was developed to overcome these limitations. In this study, we described the technical aspects and validated the accuracy of this system. Methods: A bench press was used to validate the system in the static situation. Ten healthy volunteers were measured by the new biofeedback system and a dual-belt instrumented treadmill to validate the system in the dynamic situation. Results: Bench press results showed that the sensor accurately measured peak loads up to 1000 N in the static situation. In the healthy volunteers, the load curves measured by the biofeedback system were similar to the treadmill. However, the peak loads and loading rates were lower in the biofeedback system in all participants at all speeds. Conclusions: Advanced sensor technologies used in the new biofeedback system resulted in highly accurate measurements in the static situation. The position of the sensor and the design of the biofeedback system should be optimized to improve results in the dynamic situation

Fracture of open- and closed-cell metal foams

Two closed cell aluminium foams and one open cell nickel-chromium foam were subjected to microstructural characterization, in situ fracture tests and fractography. The failure process of the open cell foam was observed to be rather ductile, while that of the closed cell foams was found to be brittle. The ductility was related to the purity of the nickel chromium alloy, resulting in necking to be the dominant source of energy dissipation during failure. The brittleness of the closed cell foams was related to the presence of precipitates and particles in the cell wall microstructure, limiting the amount of plastic dissipation. The embrittling phases were traced back to the alloy composition, viscosity enhancing additions and foaming agent.