Prototypes as Future Artifacts of Today: Towards Prototyping Alternative Futures

The design of sociotechnical futures relies on institutionalized visions but also on material artifacts. In this context, prototypes are a materialized means of exploration of potential futures. This article explores interdependencies between irritations by prototypes and critical/speculative design and argues that prototypes problematize a balance between feasibility and their potential for irritation, i.e. being incited to act differently by a prototype that does not fit into familiar practices (e.g. flying cars). We investigate the significance of the feasibility-irritation tension, first, by analyzing two case studies of prototypes from urban mobility as examples of technical feasibility in marketing and testing environments, and second, by contrasting them to the notion of prototypes as deliberately irritating artifacts within critical and speculative design practices. We offer a perspective for understanding their transformative potential. Our discussion shows how prototypes, as they are used in speculative design, might open new negotiation spaces instead of limiting futures to what seems feasible. New, irritating prototypes highlight a contingency, which is necessary to openly discussing feasible and fictional futures together.&nbsp

Optical coherence tomography guided laser cochleostomy: towards the accuracy on tens of micrometer scale

Lasers have been proven to be precise tools for bone ablation. Applying no mechanical stress to the patient, they are potentially very suitable for microsurgery on fragile structures such as the inner ear. However, it remains challenging to control the laser-bone ablation without injuring embedded soft tissue. In this work, we demonstrate a closed-loop control of a short-pulsed CO2 laser to perform laser cochleostomy under the monitoring of an optical coherence tomography (OCT) system. A foresighted detection of the bone-endosteum-perilymph boundary several hundred micrometers before its exposure has been realized. Position and duration of the laser pulses are planned based on the residual bone thickness distribution. OCT itself is also used as a highly accurate tracking system for motion compensation between the target area and the optics. During ex vivo experimental evaluation on fresh porcine cochleae, the ablation process terminated automatically when the thickness of the residual tissue layer uniformly reached a predefined value. The shape of the resulting channel bottom converged to the natural curvature of the endosteal layer without injuring the critical structure. Preliminary measurements in OCT scans indicated that the mean absolute accuracy of the shape approximation was only around 20 μm

Optical Coherence Tomography Guided Laser Cochleostomy: Towards the Accuracy on Tens of Micrometer Scale

Lasers have been proven to be precise tools for bone ablation. Applying no mechanical stress to the patient, they are potentially very suitable for microsurgery on fragile structures such as the inner ear. However, it remains challenging to control the laser-bone ablation without injuring embedded soft tissue. In this work, we demonstrate a closed-loop control of a short-pulsed CO2 laser to perform laser cochleostomy under the monitoring of an optical coherence tomography (OCT) system. A foresighted detection of the bone-endosteum-perilymph boundary several hundred micrometers before its exposure has been realized. Position and duration of the laser pulses are planned based on the residual bone thickness distribution. OCT itself is also used as a highly accurate tracking system for motion compensation between the target area and the optics. During ex vivo experimental evaluation on fresh porcine cochleae, the ablation process terminated automatically when the thickness of the residual tissue layer uniformly reached a predefined value. The shape of the resulting channel bottom converged to the natural curvature of the endosteal layer without injuring the critical structure. Preliminary measurements in OCT scans indicated that the mean absolute accuracy of the shape approximation was only around 20 mu m

Thiopurine metabolite levels in patients with atopic dermatitis and/or chronic hand/foot eczema treated with azathioprine

Background: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. Objective: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema. Methods: Azathioprine metabolite levels were measured in eczema patients during maintenance treatment (Part I) and dose escalation (Part II). Clinical effectiveness, hepatotoxicity, and bone marrow suppression were analyzed and TPMT genotype was assessed. Results: A wide variation in metabolite levels in all dose groups was observed. In Part I (32 patients), there were no significant differences in 6-TGN levels between clinical responders and non-responders (p = .806). No hepatoxicity or myelotoxicity was observed. In Part II, all 6-TGN and 6-MMP levels increased during dose escalation. Hypermethylation was observed in 2/8 patients. Conclusion: For individual eczema patients treated with azathioprine, routinely measuring 6-TGN and 6-MMP can be helpful in optimizing azathioprine dose, improving clinical effectiveness, and preventing side effects

Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage

Haloes gone MAD: The Halo-Finder Comparison Project

[abridged] We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including friends-of-friends (FOF), spherical-overdensity (SO) and phase-space based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allows halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large-scale structure of the universe. All the halo finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Via a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30-40 particles. However, also here the phase space finders excelled by resolving substructure down to 10-20 particles. By comparing the halo finders using a high resolution cosmological volume we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity, and peak of the rotation curve).Comment: 27 interesting pages, 20 beautiful figures, and 4 informative tables accepted for publication in MNRAS. The high-resolution version of the paper as well as all the test cases and analysis can be found at the web site http://popia.ft.uam.es/HaloesGoingMA

Constraining Southern Ocean air-sea-ice fluxes through enhanced observations

Air-sea and air-sea-ice fluxes in the Southern Ocean play a critical role in global climate through their impact on the overturning circulation and oceanic heat and carbon uptake. The challenging conditions in the Southern Ocean have led to sparse spatial and temporal coverage of observations. This has led to a “knowledge gap” that increases uncertainty in atmosphere and ocean dynamics and boundary-layer thermodynamic processes, impeding improvements in weather and climate models. Improvements will require both process-based research to understand the mechanisms governing air-sea exchange and a significant expansion of the observing system. This will improve flux parameterizations and reduce uncertainty associated with bulk formulae and satellite observations. Improved estimates spanning the full Southern Ocean will need to take advantage of ships, surface moorings, and the growing capabilities of autonomous platforms with robust and miniaturized sensors. A key challenge is to identify observing system sampling requirements. This requires models, Observing System Simulation Experiments (OSSEs), and assessments of the specific spatial-temporal accuracy and resolution required for priority science and assessment of observational uncertainties of the mean state and direct flux measurements. Year-round, high-quality, quasi-continuous in situ flux measurements and observations of extreme events are needed to validate, improve and characterize uncertainties in blended reanalysis products and satellite data as well as to improve parameterizations. Building a robust observing system will require community consensus on observational methodologies, observational priorities, and effective strategies for data management and discovery