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Association between biological immunotherapy for psoriasis and time to incident inflammatory arthritis: Limitations and opportunities
No full textPsoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease that affects approximately 30% of psoriasis patients. In most cases, skin disease clearly precedes the musculoskeletal disease. Some studies suggest that targeted treatment may intercept the disease course and prevent psoriasis patients from developing PsA. A recent population-based retrospective analysis in 15 501 psoriasis patients evaluated the association between different biological treatment strategies and time to incident inflammatory arthritis based on data in a US electronic health records database. A cumulative incidence of 2.6 PsA cases per 100 person-years was determined. The multivariable regression analysis revealed a significantly lower risk of developing inflammatory arthritis in patients who had been prescribed interleukin (IL)-12/23 or IL-23 inhibitors compared with tumour necrosis factor (TNF) inhibitor-treated patients, whereas there was no significant difference in risk for patients prescribed inhibitors of IL-17 versus TNF. Although the analysis was based on a large set of clinical data and the findings were rigorously evaluated, there are some limitations in interpretation due to the study design. Prospective clinical trials are missing, and retrospective data analyses from clinical trials or population-based studies show conflicting results. Overall, the recent data on prevention of PsA in patients with psoriasis support the high need to characterise biomarkers of increased risk and perform prospective clinical trials to give a clear guidance on possibilities for disease interception in psoriatic disease.9
Principles for the Effective Application of Systems Engineering: A Systematic Literature Review and Application Use Case
No full text13071312The implementation of Systems Engineering (SE) offers a solution for organizations facing challenges from digitalization and increasing product complexity and interconnectivity. However, the implementation of SE company-wide requires a holistic approach that considers human and organizational factors beyond just technology and technical processes. This paper presents a systematic literature review (SLR) that aimed to determine the key principles for the effective application of SE in industrial practice. Through open, axial, and selective coding, 12 key principles were identified. Finally, an application example is given to show how the principles can be used to improve the process of the offer phase in special purpose machinery
Pulsed scattering events during HEL atmospheric propagation
No full textWhen employing a High Energy Laser (HEL) in an outdoor environment, a laser safety evaluation has to consider the energy scattered by aerosols during the propagation of the laser. We developed a measurement device SeLMA (ScattEred Laser Measurement Assembly), comprising a set of optical receivers installed on an arc to perform an angularly- and temporally-resolved measurement of this scattered radiation. Measurements with high laser emission intensities revealed powerful pulses in the scattered radiation with the peak power significantly exceeding the average level of the signal. Radiative intensity distribution of the scattered emission was measured in a controlled laboratory environment at various irradiance levels in the laser beam. These results were used for preliminary evaluations of the off-axis ocular hazard distance for a typical HEL operation scenario
Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients
No full text195204Introduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. Conclusion: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.36
A robust, viable, and resource sparing HPLC-based logP method applied to common drugs
No full textReliable, experimentally determined partition coefficient P (logP) for most drugs are often unavailable in the literature. Many values are from in silico predictions and may not accurately reflect drug lipophilicity. In this study, a robust, viable, and resource sparing method to measure logP was developed using reverse phase high performance liquid chromatography (RP-HPLC). The logP of twelve common drugs was measured using calibration curves at pH 6 and 9 that were created using reference standards with well-established logP. The HPLC method reported here can be used for high throughput estimation of logP of commonly used drugs. LogP values here showed general agreement with the other few HPLC-based literature logP values available. Additionally, the HPLC-based logP values found here agreed partially with literature logP values found using other methodologies (±10%). However, there was no strong agreement since there are few experimentally determined literature logP values. This paper shows a facile method to estimate logP without using octanol or computational approaches. This method has excellent promise to provide reliable logP values of commonly used drugs available in literature. A larger pool of reliable logP values of commonly drugs has promise to improve quality of medicinal chemistry and pharmacokinetic (PK) models.64
A Model of Driver Readiness After Sleep
No full text358371In this contribution, we propose a model of driver readiness after sleep. It is supposed to cover user states occuring in SAE levels L3 and L4. We propose four states for our model: "Ready to drive", "Relaxing", "Sleeping", and "Affected by Sleep Inertia". We provide first suggestions on transitions between the states and on appropriate transition times. We describe the three states "Relaxing", "Sleeping", and "Affected by Sleep Inertia" in a chapter each as they are new states not occuring in L0, L1, and L2 models
Heterosystem-integrated carbon nanotube sensors for on-ASIC condition monitoring
No full text458461This work demonstrates modular integrability of CNT-based nanodevices on top of the BEOL interconnect stack of a conventional ASIC enabling additional condition monitoring features in the framework of advanced prognostic health monitoring concepts. We highlight in particular a Nanoelectromechanical system (NEMS) technology featuring suspended CNTs with controllable prestrain to ensure detectability of smallest strain variation along with changes in the packing environment. The NEMS is generated by a CMOS-compatible surface micromachining process flow making use of a relaxation of prestrained layer stacks after local removal of a sacrificial-layer. Corresponding critical dimensions and design are derived from FE-simulations. The impressed strain into the nanomaterial is confirmed by Raman spectroscopy. According to this analysis, the CNT specific G-band exhibits a clear blue shift of 6.2 cm-1 upon membrane release indicating on axially acting tensile strain between up to 0.8%. For the piezoresistive sensors this corresponds to a significant reduction of the strain detection limit to 30 MPa and gauge factor of up to 644, which is around 5 times higher than for conventional Si-based strain gauges
Feasibility of in-orbit 3D printing of continuous fibre reinforced composites
No full textIn-Space manufacturing (ISM) is actively being investigated as a method to fabricate large, complex, yet resource efficient structures in orbit. Novel technologies such as fused filament fabrication (FFF) based additive manufacturing (AM) using thermoplastics have been identified as potential sustainable production technology for ISM due to their inherent manufacturing flexibility and low waste generation. Fibre- reinforced composites have been hypothesized to facilitate ISM while simultaneously realising functional structures with strength, modulus and weight advantage. In this study, we proposed and established an adapted FFF process that enables manufacturing of continuous fibre reinforced composite (CFRC) structures in space, beyond the confines of the International Space Station. Using continuous fibre tow and thermoplastic filament as feedstocks, a flexible printing setup was developed. It enables in-situ impregnation and coextrusion of tailored CFRC to directly print composite structures with desired matrix-fibre combination for a specific use case. First, the feasibility of in-situ impregnation and coextrusion process to function in the low-pressure space environment was assessed. The setup was successfully tested in a vacuum chamber using a modified 3D printer, and the impact of low pressure on FFF manufactured CFRC was studied. Initial investigations showed positive results with similar fibre impregnation for the samples produced in low-pressure environment compared to samples manufactured in atmosphere. Next, the viability of the proposed setup to fabricate large, free-form composite structures in the free-floating space environment was evaluated. The proposed coextrusion setup was used to print CFRC trusses in a simulated free-floating environment using the Experimental Lab for Proximity Operations and Space Situational Awareness (ELISSA) air bearing table at the Institute of Space Systems in TU Braunschweig. Combining the reach of a free-flying satellite with the accuracy afforded by a robotic arm in conjunction with coextruding print-head, and using a continuous toolpath, printing of complex, free-standing CFRC structures with sub-millimetre resolution was successfully demonstrated
Structure and Organization of Product Development Projects
No full textThis book conveys useful knowledge, skills and behaviour that an engineer who is responsible for product development/project management often needs, but which is not given enough attention in the usual engineering education. It goes beyond the specialist knowledge into the human domain, because technical and/or organisational difficulties are in fact always based on human problems. The book is aimed at professionals and managers working in the development of machines, apparatus, equipment and the like, including the responsible organizational managers
Numerical model of a large scale monopile test in non-cohesive soil
No full text16221628Accurate modelling of the pile-soil interaction for offshore support structures is a great challenge for the industry. A main influencing parameter is the installation technique and the effects to the surrounding soil. As the numerical modelling of a pile installation process is time consuming, piles are usually modelled numerically as wished-in-place structures. When using this modelling strategy, the initial soil parameters should be adapted, depending on the installation technique. Especially for offshore piles, there are currently no general approaches to consider these installation effects. In this contribution a brief summary regarding impact and vibratory driven installation and their influence on the lateral load-bearing behavior is given. Furthermore, experimental results as well as a hypoplastic numerical prediction of a large-scale impact driven monopile test are presented and their results are evaluated. Finally, conclusions about the consideration of installation effects when modeling the pile load bearing behavior are drawn