Search

Dry eye disease affects millions of people worldwide, causing pain, vision disturbance, and reduced productivity. Meibomian gland dysfunction, a major cause of dry eye, is characterized by chronic glandular inflammation, thickening of the meibum, obstruction of terminal ducts, and glandular atrophy. Treatment of meibomian gland dysfunction can utilize heat and pressure applied to the meibomian glands, increasing meibum expression. With self-treatments, however, not all patients achieve lasting improvement, and compliance is often low. In-office thermal systems offer a second line of treatment and could be a much-needed addition for patients who do not respond to conventional treatment. We critically evaluated the efficacy and safety of LipiFlow, iLux, and TearCare based on existing literature. While the studies found a single in-office thermal treatment to be safe and effective in improving short-term signs and symptoms in patients with dry eye, long-term efficacy needs to be further evaluated. Thus, well-controlled, long-term efficacy studies are warranted to draw clear conclusions. The treatment seemed to provide rapid relief of symptoms that may last up to 1 year, but at a considerably higher cost than the at-home treatments. The choice of treatment depends on cost, compliance with at-home treatment, and personal preference.

Laser material deposition (LMD) is a widely used coating process in industry. However, to increase its economic appeal, higher process speeds are required. The solution to this challenge is an innovative modification known as extreme high-speed laser material deposition (EHLA). EHLA allows for an impressive increase in process speed from 2 m/min for conventional LMD to 500 m/min. With the ability to adjust process parameters, EHLA can generate tailor-made surface properties, expanding its potential application beyond current industrial uses. In this novel study, we explore the effects of relative positioning between tools (laser beam and powder–gas jet) and substrate on the surface properties of EHLA coatings. By laterally and axially offsetting the tools, the proportional energy coupling of the laser radiation into the powder–gas jet and substrate can be modified. Altering the position of the powder–gas jet can also affect the weld pool flow or number of particle attachments, thereby affecting surface properties. This approach allows for the adjustment of surface roughness over a wide range—from smooth, quasi-laser-polished surfaces to rough surfaces covered with particle adhesions.

Background and Objectives: Dry eye disease (DED) is a common and very symptomatic pathology that affects normal daily activity. The aim of the study was to evaluate the efficacy of plasma rich in growth factors (PRGF) added to one routine treatment protocol for DED (artificial tears substitutes, lid hygiene, and anti-inflammatory therapy). Materials and Methods: Patients were divided into two groups of treatment: standard treatment group (n = 43 eyes) and PRGF group (n = 59). Patients’ symptomatology (inferred from OSDI and SANDE questionnaires), ocular inflammation, tear stability, and ocular surface damage were analyzed at baseline and after 3 months of treatment. Results: OSDI test scores were significantly lower in both groups (p < 0.001). SANDE frequency test scores also improved statistically, with differences between groups (p = 0.0089 SANDE frequency and p < 0.0119 SANDE severity). There was a greater reduction in ocular redness (ocular inflammation) in the PRGF group (p < 0.0001) and fluorescein tear break-up time was significantly improved in the PRGF group (p = 0.0006). No significant changes were found in terms of ocular surface damage. No adverse events were obtained in either group. Conclusions: The addition of PRGF to the standard treatment of DED, according to the results obtained, proved to be safe and produced an improvement in ocular symptomatology and signs of inflammation, particularly in moderate and severe cases, when compared to standard treatment.

Additive manufacturing technologies have numerous advantages over conventional technologies; nevertheless, their production process can lead to high residual stresses and distortions in the produced parts. The use of numerical simulation models is presented as a solution to predict the deformations and residual stresses resulting from the printing process. This study aimed to predict the tensions and distortions imposed in the gear repair process by directed energy deposition (DED). First, the case study proposed by National Institute of Standards and Technology (NIST) was analyzed to validate the model and the numerically obtained results. Subsequently, a parametric study of the influence of some of the parameters of DED technology was carried out. The results obtained for the validation of the NIST benchmark bridge model were in agreement with the results obtained experimentally. In turn, the results obtained from the parametric study were almost always in line with what is theoretically expected; however, some results were not very clear and consistent. The results obtained help to clarify the influence of certain printing parameters. The proposed model allowed accounting for the effect of residual stresses in calculating the stresses resulting from gear loading, which are essential data for fatigue analysis. Modeling and simulating a deposition process can be challenging due to several factors, including calibrating the model, managing the computational cost, accounting for boundary conditions, and accurately representing material properties. This paper aimed to carefully address these parameters in two case studies, towards reliable simulations.

Aluminum alloy is an important material used in railway train structures. It is of great significance to repair aluminum alloy through directional energy deposition to reduce cost and improve the performance of the aluminum alloy. In this study, 7N01 aluminum alloy was repaired by means of laser-directed energy deposition (DED) with the powder of Sc-modified Al-Zn-Mg aluminum alloy as raw material. The microstructure and mechanical properties of the repaired specimens were studied through the metallographic microscope, scanning electron microscope, electron backscatter diffraction, universal tensile test, and Vickers hardness test in combination. The results show that the bonding interface of the repaired aluminum alloy is satisfactory, and the porosity is 2.8%. The grains in the repaired area are the columnar crystals growing vertically along the boundary of the melt pool with an obvious temperature gradient. Fine equiaxed crystals are distributed along the boundary of the melt pool, and Al3(Sc,Zr) particles play a role in grain refinement. The average grain size of the fine grain area in the repair zone next to the fusion zone is 9.1 μm, and the average grain size of the coarse grain area is 20 μm. The average tensile strength in the area of repair approaches 349 MPa, which is 91% that of the base material, and the elongation rate is 10.9%, which is 53.2% that of the base material. The hardness ranges between 122 HV and 131 HV, which is comparable to the base material. However, there is a significant decrease in the tensile strength and hardness of the base material (heat-affected zone).

Background: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described.Purpose: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED.Methods: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated.Findings: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development.Conclusion: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED.

Samples of 316L SS were manufactured by Laser Engineered Net Shaping (LENS®) using different technological parameters. The deposited samples were investigated in terms of microstructure, mechanical properties, phase content and corrosion resistance (salt chamber and electrochemical corrosion). Parameters were chosen to obtain a proper sample built for layer thicknesses of 0.2, 0.4 and 0.7 mm by changing the laser feed rate while keeping the powder feed rate constant. After a comprehensive analysis of the results, it was found that the manufacturing parameters slightly affected the resulting microstructure and also had a minor impact (almost undetectable considering the uncertainty of the measurement) on the mechanical properties of samples. Decreases in resistance to electrochemical pitting corrosion and environmental corrosion with an increased feed rate and a decrease in layer thickness and grain size were observed; however, all additively manufactured samples were found to be less prone to corrosion than the reference material. In the investigated processing window, no influence of deposition parameters on the phase content of the final product was found—all the samples were found to possess austenitic microstructure with almost no detectable ferrite.

(1) This work answers the question of whether and to what extent there is a significant difference in mechanical properties when different additive manufacturing processes are applied to the material 1.2709. The Laser-Powder-Bed-Fusion (L-PBF) and Laser-Metal-Deposition (LMD) processes are considered, as they differ fundamentally in the way a part is manufactured. (2) Known process parameters for low-porosity parts were used to fabricate tensile strength specimens. Half of the specimens were heat-treated, and all specimens were tested for mechanical properties in a quasi-static tensile test. In addition, the material hardness was determined. (3) It was found that, firstly, heat treatment resulted in a sharp increase in mechanical properties such as hardness, elastic modulus, yield strength and ultimate strength. In addition to the increase in these properties, the elongation at break also decreases significantly after heat treatment. The choice of process, on the other hand, does not give either process a clear advantage in terms of mechanical properties but shows that it is necessary to consider the essential mechanical properties for a desired application.

Wire and Arc Additive manufacturing (WAAM) is a Direct Energy Deposition process suitable for the manufacture of large aluminium components. Additive Manufacturing can enable the production of functionally graded structure which could be done by integrating the substrate required to start the deposition into the final component. This paper aims to assess the possibility of including a substrate in a component by investigating the mechanical performances of the interface between a wrought plate and WAAM deposit. Four substrates alloys and 2319 WAAM alloy were investigated. Inter-layer rolling and heat treatment, process steps known for improving the properties of WAAM deposit, were implemented. Each interface was examined using microhardness profiles, tensile tests, post rupture fractography and microstructural analysis. The WAAM deposit hardness was lower than that of the substrate in the as-deposited condition. Although the interface had no impact when using the same alloy for both substrate and wire, the weakest point of the combination was at the interface in dissimilar alloy combination. Heat treatment reduced the properties difference between the substrate and WAAM deposit. Inter-pass rolling strengthen the WAAM deposit without impacting the substrate and eliminated the micro crack that occasionally formed in the fusion zone in the as-deposited condition.

Directed Energy Deposition (DED) additive manufacturing has recently been adopted in the industry for the build-up of structural components with weld lengths up to kilometers. As with all welding processes, DED suffers from thermal distortion, causing loss of dimensional accuracy and risk of cracking. Currently, process optimization with objective to minimize distortion requires expensive experimental trial-and-error. With numerical simulation of the DED process, this distortion compensation can be performed virtually, significantly reducing experimental trials. Although such approaches are generally available, their widespread adoption is currently being hampered by long computational times for large builds. This work presents a novel approach to reduce the calculation time by a simplification of the transient heat-source motion. This approach is assessed in terms of result accuracy for an industrial-scale component by progressively reducing the resolution of the heat-source motion. Calculation times as well as distortions in comparison to experimental trials are investigated.

Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface.

Paul Karpecki,1 David Wirta,2 Smajo Osmanovic,3 Kavita Dhamdhere4 1Kentucky Eye Institute, Lexington, KY, USA; 2Eye Research Foundation, Newport Beach, CA, USA; 3Arlington Eye Physicians Llc, Arlington Heights, IL, USA; 4Sight Sciences, Inc., Menlo Park, CA, USACorrespondence: Kavita Dhamdhere 4040 Campbell Avenue, Suite 100, Menlo Park, CA 94025, USATel +1 650-223-4062Fax +1 877-266-1144Email kdhamdhere@sightsciences.comPurpose: This study evaluated the safety and effectiveness of TearCare® System to treat the signs and symptoms of dry eye disease (DED).Methods: In this multicenter, prospective, post-market, exploratory, interventional trial, 58 eyes (29 subjects) received a single TearCare procedure and were assessed at baseline, post-procedure 1-week and 1-month. Effectiveness was assessed as mean change from baseline in tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), total Meibomian Gland Secretion Score (MGSS), and corneal/conjunctival staining. Adverse events (AE) and changes in visual acuity were used to asses safety.Results: The baseline TBUT of 3.7± 1.1 seconds was improved by 2.6± 1.6 (70%) seconds at 1-week and by 3.1± 2.2 (84%) seconds at 1-month (p < 0.0001). Mean baseline OSDI of 54.9± 20.2 improved by 17.9± 20.9 at 1-week and 25.8± 24.3 at 1-month (p < 0.001). A clinically meaningful improvement was seen in 83% of subjects as per the Miller-Plugfelder definition and 66% of subjects improved by at least 1 OSDI category. The baseline MGSS of 5.6± 4.0 improved by 9.3± 4.0 at 1-week and 8.8± 5.8 at 1-month (p < 0.0001). Corneal and conjunctival staining improved by 1.4± 2.8 and 1.2± 2.9 from a mean baseline of 4.8± 2.5 and 5.9± 3.2, respectively. Moreover, similar trajectories of improvement were observed for subgroups of subjects stratified by severity. Subjects with more severe gland obstruction at baseline had greater improvements in TBUT and staining compared to the less severe subgroup. No device-related adverse events or significant changes in visual acuity were observed.Conclusion: These results suggest that single TearCare procedure is safe and effective in treating signs/symptoms of DED. Significant improvements were seen in all subjects (100%) in all signs and symptoms of DED within 1-week of treatment and 83% subjects experienced clinically meaningful symptom relief. Additionally, TearCare seems to be effective in treating DED associated with all severities of meibomian gland obstruction.Keywords: meibomian gland dysfunction, MGD, thermal therapy, TearCare procedure, evaporative dry eye disease, DED

Paul Karpecki,1 David Wirta,2 Smajo Osmanovic,3 Kavita Dhamdhere4 1Kentucky Eye Institute, Lexington, KY, USA; 2Eye Research Foundation, Newport Beach, CA, USA; 3Arlington Eye Physicians Llc, Arlington Heights, IL, USA; 4Sight Sciences, Inc., Menlo Park, CA, USACorrespondence: Kavita Dhamdhere 4040 Campbell Avenue, Suite 100, Menlo Park, CA 94025, USATel +1 650-223-4062Fax +1 877-266-1144Email kdhamdhere@sightsciences.comPurpose: This study evaluated the safety and effectiveness of TearCare® System to treat the signs and symptoms of dry eye disease (DED).Methods: In this multicenter, prospective, post-market, exploratory, interventional trial, 58 eyes (29 subjects) received a single TearCare procedure and were assessed at baseline, post-procedure 1-week and 1-month. Effectiveness was assessed as mean change from baseline in tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), total Meibomian Gland Secretion Score (MGSS), and corneal/conjunctival staining. Adverse events (AE) and changes in visual acuity were used to asses safety.Results: The baseline TBUT of 3.7± 1.1 seconds was improved by 2.6± 1.6 (70%) seconds at 1-week and by 3.1± 2.2 (84%) seconds at 1-month (p < 0.0001). Mean baseline OSDI of 54.9± 20.2 improved by 17.9± 20.9 at 1-week and 25.8± 24.3 at 1-month (p < 0.001). A clinically meaningful improvement was seen in 83% of subjects as per the Miller-Plugfelder definition and 66% of subjects improved by at least 1 OSDI category. The baseline MGSS of 5.6± 4.0 improved by 9.3± 4.0 at 1-week and 8.8± 5.8 at 1-month (p < 0.0001). Corneal and conjunctival staining improved by 1.4± 2.8 and 1.2± 2.9 from a mean baseline of 4.8± 2.5 and 5.9± 3.2, respectively. Moreover, similar trajectories of improvement were observed for subgroups of subjects stratified by severity. Subjects with more severe gland obstruction at baseline had greater improvements in TBUT and staining compared to the less severe subgroup. No device-related adverse events or significant changes in visual acuity were observed.Conclusion: These results suggest that single TearCare procedure is safe and effective in treating signs/symptoms of DED. Significant improvements were seen in all subjects (100%) in all signs and symptoms of DED within 1-week of treatment and 83% subjects experienced clinically meaningful symptom relief. Additionally, TearCare seems to be effective in treating DED associated with all severities of meibomian gland obstruction.Keywords: meibomian gland dysfunction, MGD, thermal therapy, TearCare procedure, evaporative dry eye disease, DED

The Directed Energy Deposition process is used in a wide range of applications including the repair, coating or modification of existing structures and the additive manufacturing of individual parts. As the process is frequently applied in the aerospace industry, the requirements for quality assurance are extremely high. Therefore, more and more sensor systems are being implemented for process monitoring. To evaluate the generated data, suitable methods must be developed. A solution, in this context, was the application of artificial neural networks (ANNs). This article demonstrates how measurement data can be used as input data for ANNs. The measurement data were generated using a pyrometer, an emission spectrometer, a camera (Charge-Coupled Device) and a laser scanner. First, a concept for the extraction of relevant features from dynamic measurement data series was presented. The developed method was then applied to generate a data set for the quality prediction of various geometries, including weld beads, coatings and cubes. The results were compared to ANNs trained with process parameters such as laser power, scan speed and powder mass flow. It was shown that the use of measurement data provides additional value. Neural networks trained with measurement data achieve significantly higher prediction accuracy, especially for more complex geometries.

Background: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described. Purpose: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED. Methods: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated. Findings: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development. Conclusion: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED. This research was partly funded by NFR 271555 grant by the Norwegian Research Council, through the Medical Student Research Program. D.A. Dartt was supported by grants from the US NIH: R01 EY019470, R01 EY029789 and R01 EY021292.

Resumo Os processos de Manufatura Aditiva (MA) de Metais permitem criar peças tridimensionais através da adição progressiva de finas camadas de material. Estes processos se enquadram em duas grandes categorias, denominadas Fusão em Leito de Pó e Deposição por Energia Direcionada. A compreensão física dos processos de MA pode fornecer uma visão holística sobre as sensibilidades aos parâmetros de processo. Já a modelagem computacional destes processos não só pode fornecer uma visão importante dos fenômenos físicos que levam às propriedades finais do material e à qualidade do produto, mas também os meios para explorar o espaço de projeto, visando criar produtos funcionais. Esta revisão introdutória foca na MA de materiais metálicos, particularmente nas questões de modelagem física e numérica. São apresentadas considerações sobre os diversos fenômenos físicos atuantes, métodos computacionais mais empregados, técnicas para realizar a modelagem e suas respectivas validações, demonstrando os desafios e limitações atuais, assim como as perspectivas futuras da simulação computacional aplicada aos processos de MA. Abstract Additive Manufacturing (AM) processes of metals allow creating three-dimensional parts through the progressive addition of thin layers of material. These processes fall into two major categories, called Powder Bed Fusion and Directed Energy Deposition. Physical understanding of the AM processes can provide a holistic view of the sensitivity to process parameters. Computational modeling of these processes can not only provide an important view of the physical phenomena that lead to the final properties of the material and quality of the product, but also the means to explore the design space, in order to create functional products. This introductory review focuses on the AM of metallic materials, particularly on issues of physical and numerical modeling. Considerations are presented about the various physical phenomena at work, most used computational methods, techniques to perform the modeling and their respective validations, demonstrating the current challenges and limitations, as well as the future perspectives for computer simulations applied to AM processes.

Heat exchangers for use in propulsion applications are very critical components because they must be efficient, compact and light and often operate with working fluids at extreme temperatures or pressures or both. Various components and systems use heat exchangers such as combustion chambers of gas turbines and internal combustion engines, fuel cells (air supply and thermal management), electric batteries (thermal management), evaporators and recuperators of waste-heat-to-power systems, and rocket engines. Even if the results are more generally applicable, the heat exchangers applications to which this study is more closely related are regeneratively cooled rocket nozzles and chambers, and repressurization systems for the launch vehicles. These components are often thin-walled and contain pressurized fluids, like propellants at cryogenic or elevated temperatures. Given that the environments that these propulsion components must endure are challenging, the manufacturing to meet these specifications often require long lead times due to specialty processes and unique tooling associated with the combined thin-wall integral channel and large-scale structures. Additive manufacturing (AM) offers programmatic advantages for reduction in processing time and cost in addition to various technical advantages, including the possibility to achieve enhanced hardware complexity targeted to superior performance, part consolidation, and the capability of processing of novel alloys. While AM is already being utilized for heat exchanger components in propulsion applications, almost all these AM components are made by means of Laser Powder Bed Fusion (L-PBF). L-PBF allows for fine features but is rather limited with respect to the overall size of the components that can be manufactured. Recent developments are maturing the Laser Powder Directed Energy Deposition (LP-DED) process which may be used, for example, to make integral channel thin-wall regeneratively-cooled rocket nozzles with diameters greater than 1 m. This paper highlights some integral channel heat exchanger demonstrator hardware applications of LP-DED, as well as the characterization of this process in combination with the use of the NASA HR-1 alloy. To properly utilize LP-DED for heat exchanger manufacturing, various aspects are being characterized such as geometry limitations, measurement of surface texture and geometric angled surfaces, surface enhancements for internal channels, and material evaluation. NASA HR-1 (Fe-Ni-Cr) is a high strength hydrogen resistant superalloy developed for use in aerospace applications, such as heat exchangers. Some aspects and considerations about the design of heat exchangers are summarized together with data relevant to LP-DED manufacturing in combination with the NASA HR-1 alloy. Microchannels were successful deposited down to 2.54 mm and 1 mm wall thickness, wall angles of 30°, both with high reproducibility. It was also found that the areal surface roughness is highly dependent on the size of the powder feedstock used for deposition. The characterization of these LP-DED features is critical for fluid flow and heat transfer predictions as it can be exploited to enhance heat transfer at the cost of increased pressure drop.

This thesis aims to investigate whether additive manufacturing is applicable in manufacturing the 1N thruster option that Bradford Ecaps offers. Therefore, the nozzle design is of particular interest as AM provides accessibilities to manufacturing complex structures. The current Ecaps 1N thruster has an operating thrust lifespan that exceeds the required lifespan commonly needed for the majority of customers. With AM, an increase in production throughput and optimization of nozzle design is possible. A candidate material, a platinum group metal, was picked for a future 1N thruster prototype concerning the limiting operating constraints. Computational fluid analysis was performed to investigate different contour nozzles to investigate the possibility of improving the performance of the Bradford ECAPS 1N thruster. AMATLAB code was developed to model the contour nozzles, and ANSYS Fluent was used for the computational analysis. Three different nozzle geometries were evaluated to investigate the overall performance of the expanding exhaust gas and thrust properties in vacuum conditions. Configuration 1. which had an extended nozzle was selected as a solution since it eliminatedthe interferences with the continuum. The Nasa CEA code was used to generate the fluid gas properties. No substantial performance gain was observed for the 1N thruster. This was found to be due to the boundary-dominated flow exhibited in the nozzle. A conical nozzle was found to work comparatively well. Detta examensarbete syftar till att undersöka om additiv tillverkning (AM) är tillämplig vid tillverkning av Bradford Ecaps 1N raketmotor. Därför är munstycksdesignen av särskilt intresse eftersom AM ger möjlighet för tillverkning av komplexa strukturer. Den nuvarande Ecaps 1N-motorn har en livslängd som överstiger den livslängd som krävs för de flesta kunder. Med AM är ökning av produktionsgenomströmningen och optimering av munstycksdesign möjlig. Ett kandidatmaterial, en metall i platinagruppen, valdes ut för en framtida 1N prototyp med hänvisning till de begränsande driftsbegränsningarna. Beräkningsflödesanalys utfördes för att undersöka olika konturmunstycken för att undersöka möjligheten till att förbättra prestandan hos Bradford ECAPS 1N framdrivningssystem. En MATLAB-kod utvecklades för att modellera konturmunstyckena och ANSYS Fluent användes för beräkningsanalysen. Tre olika munstycksgeometrier utvärderades för att undersöka den totala prestandan hos de expanderande avgaserna och dragkraftsegenskaperna under vakuumförhållanden. Konfiguration 1. som hade ett förlängt munstycke valdes som en lösning eftersom detta eliminerade interferenserna med kontinuumet. Nasa CEA-koden användes för att generera fluidens gasegenskaper. Ingen betydande prestandaökning observerades för 1N motorn. Detta visade sig bero på det gränsskiktsdominerade flödet som uppvisades i munstycket. Ett koniskt munstycke visade sig fungera relativt bra.

Additive Manufacturing (AM) offers new design and manufacturing opportunities of thin-wall microchannel heat exchangers for aerospace and industrial applications. Laser Powder Directed Energy Deposition (LP-DED) is an AM process providing large scale manufacturing of thin-wall microchannel heat exchangers. Successful industrialization of the LP-DED process requires critical quantification and understanding of the metallurgical, geometric, and process limitations. Specifically, understanding the as-built surface texture, inclusive of roughness and waviness, is significant due to its effects on the friction factor and pressure drop within a heat exchanger. This experimental study completed a design of experiments (DOE) to determine the critical build parameters that impact surface texture for enclosed thin-wall samples. This study summarizes the characterization work of the LP-DED process for 1 mm enclosed walls with an Fe–Ni–Cr (NASA HR-1) alloy. The LP-DED parameters including laser power, powder feedrate, travel speed, layer height, and rotary atomized powder feedstock were modified in the experiment. An evaluation of the DOE samples and resulting surface texture is provided along with conclusions from these experiments. Results indicate that 3D areal and 2D profile (directional) surface texture is estimated by 2x the powder diameter that becomes captured or partially melted on the trailing edge of the melt pool. The fine powder showed a higher sensitivity to parameter changes but resulted in a higher density material and 23% reduction in roughness. Surface texture was also shown to vary between closed channel shapes (internal) due to ricochets, recirculation, and higher volume of powder available to bond compared to external (outer) surfaces. The understanding of the LP-DED process as-built surface texture is essential to fluid flow applications such as heat exchanges and can modify performance for enhanced heat transfer or can be a detriment to pressure drop.

Heat exchangers for use in propulsion applications are very critical components because they must be efficient, compact and light and often operate with working fluids at extreme temperatures or pressures or both. Various components and systems use heat exchangers such as combustion chambers of gas turbines and internal combustion engines, fuel cells (air supply and thermal management), electric batteries (thermal management), evaporators and recuperators of waste-heat-to-power systems, and rocket engines. Even if the results are more generally applicable, the heat exchangers applications to which this study is more closely related are regeneratively cooled rocket nozzles and chambers, and repressurization systems for the launch vehicles. These components are often thin-walled and contain pressurized fluids, like propellants at cryogenic or elevated temperatures. Given that the environments that these propulsion components must endure are challenging, the manufacturing to meet these specifications often require long lead times due to specialty processes and unique tooling associated with the combined thin-wall integral channel and large-scale structures. Additive manufacturing (AM) offers programmatic advantages for reduction in processing time and cost in addition to various technical advantages, including the possibility to achieve enhanced hardware complexity targeted to superior performance, part consolidation, and the capability of processing of novel alloys. While AM is already being utilized for heat exchanger components in propulsion applications, almost all these AM components are made by means of Laser Powder Bed Fusion (L-PBF). L-PBF allows for fine features but is rather limited with respect to the overall size of the components that can be manufactured. Recent developments are maturing the Laser Powder Directed Energy Deposition (LP-DED) process which may be used, for example, to make integral channel thin-wall regeneratively-cooled rocket nozzles with diameters greater than 1 m. This paper highlights some integral channel heat exchanger demonstrator hardware applications of LP-DED, as well as the characterization of this process in combination with the use of the NASA HR-1 alloy. To properly utilize LP-DED for heat exchanger manufacturing, various aspects are being characterized such as geometry limitations, measurement of surface texture and geometric angled surfaces, surface enhancements for internal channels, and material evaluation. NASA HR-1 (Fe-Ni-Cr) is a high strength hydrogen resistant superalloy developed for use in aerospace applications, such as heat exchangers. Some aspects and considerations about the design of heat exchangers are summarized together with data relevant to LP-DED manufacturing in combination with the NASA HR-1 alloy. Microchannels were successful deposited down to 2.54 mm and 1 mm wall thickness, wall angles of 30°, both with high reproducibility. It was also found that the areal surface roughness is highly dependent on the size of the powder feedstock used for deposition. The characterization of these LP-DED features is critical for fluid flow and heat transfer predictions as it can be exploited to enhance heat transfer at the cost of increased pressure drop.

International audience; The two additive manufacturing processes Powder Bed Fusion (LPBF) and Directed Energy Deposition (DED) have different geometrical resolutions and production flexibilities, making their hybridization attractive. LPBF microstructure displays fine grains, with weak preferential crystal orientation. DED generates a highly textured and inhomogeneous microstructure with equivalent grains diameters ranging from a few micrometers to over a millimeter. The microstructure of the hybrid LPBF-DED sample is the addition of these two microstructures with an interface free from cracks or particular pores. The effect of this strong heterogeneity of the hybrid microstructure on mechanical behavior is analyzed by tensile tests instrumented with local strain gauges, others using digital image correlation method and finally on samples tested inside a scanning electron microscope. This multi-scale characterization showed that the difference in the elastic properties causes the localization of the strain field and generates a plastic incompatibility at the interface. An optimized heat treatment leads to isotropic and homogeneous hybrid microstructure, with a larger DED grain size. It leads to identical plasticity mechanisms during tensile tests and lowers the strain gradient around the interface.

55. CIRP Conference on Manufacturing Systems, CMS 2022, Lugano, Switzerland, 29 Jun 2022 - 1 Jul 2022; Procedia CIRP 107, 1539-1544 (2022). doi:10.1016/j.procir.2022.05.188 special issue: "Leading manufacturing systems transformation – Proceedings of the 55th CIRP Conference on Manufacturing Systems 2022 / Edited by Emanuele Carpanzano, Claudio Boër, Anna Valente", Published by Elsevier, Amsterdam [u.a.]

Directed Energy Deposition (DED) Additive Manufacturing process for metallic parts are becoming increasingly popular and widely accepted due to their potential of fabricating parts of large dimensions. The complex thermal cycles obtained due to the process physics results in accumulation of residual stress and distortion. However, to accurately model metal deposition heat transfer for large parts, numerical model leads to impractical computation time. In this work, a 3D transient finite element model with Quiet/Active element activation is developed for modeling metal deposition heat transfer analysis of DED process. To accurately model moving heat source, Goldak’s double ellipsoid model is implemented with small enough simulation time increment such that laser moves a distance of its radius over the course of each increment. Considering thin build-wall of Stainless Steel 316L fabricated with different process parameters, numerical results obtained with COMSOL 5.6 Multi-Physics software are successfully validated with experiment temperature data recorded at the substrate during the fabrication of 20 layers. To reduce the computation time, elongated ellipsoid heat input model that averages the heat source over its entire path is implemented. It has been found that by taking such large time increments, numerical model gives inaccurate results. Therefore, the track is divided into several sub-tracks, each of which is applied in one simulation increment. In this work, an investigation is done to find out the correct simulation time increment or sub-track size that leads to reduction in computation time (5–10 times) but still yields sufficiently accurate results (below 10% of relative error on temperature). Also, a Correction factor is introduced that further reduces computation error of elongated heat source. Finally, a new correlation is also established in finding out the correct time increment size and correction factor value to reduce the computation time yielding accurate results.

Aluminium zinc alloys are widely used in the aerospace industry due to their high strength. However, only a few studies have been reported on the additive manufacture of aluminium zinc alloys. This rarity is due to the difficulties occurring during the fusion processing of these alloys and to the lack of available raw material. This paper presents an alternative process used for the deposition of aluminium zinc alloys. In this study, a Wire Laser Arc Additive Manufacture (WLAAM) system was used. This consisted of a gas metal arc power source, used to generate the melt pool, and a laser beam applied to control the melt pool size. By using this approach, it was possible to produce an elongated melt pool and feed zinc into it with a cold wire without compromising the process stability. A welding camera along with a system measuring the arc voltage and current was used to monitor the process. Different process parameters and configurations were investigated along with their effect on process stability and deposited material microstructure. A very high zinc concentration was achieved in the deposited material without macro-segregation.

Purpose To evaluate 6-month treatment benefits with lifitegrast ophthalmic solution 5% in symptomatic dry eye patients. Setting Retrospective chart analysis. Method A retrospective chart review was conducted in 168 patients (111 females and 57 males) who presented with symptoms of chronic dry eye disease and were treated with lifitegrast 5% ophthalmic solution for 6 months. Collected symptom data included improvement of eye dryness, tearing, eye pain, fluctuation in vision, foreign body sensation, itching, grittiness, burning and contact lens intolerance if applicable. Collected clinical signs included changes in superficial punctate keratitis, corneal fluorescein staining, conjunctival hyperemia and presence of tear debris. Results Treatment with lifitegrast ophthalmic solution 5% twice daily for 6 months significantly improved majority of dry eye symptoms reported by patients. Improvements were also observed in corneal and conjunctival staining and tear debris for most of the patients reviewed. Conclusion Treatment with lifitegrast twice a day for 6 months improved both signs and symptoms of chronic dry eye.

Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P

Simple Summary Dutch elm disease (DED) has been killing elms for more than a century in northern Europe; the trees’ health status has worsened substantially in recent decades. Elm bark beetles Scolytus spp. are vectors of DED. Our aim was to estimate the distribution range of elm bark beetles and to detect potential new vectors of DED agents in northern Europe. Beetles were caught with bottle traps and manually. Then DNA from each specimen was extracted and analysed by the third generation sequencing method. DED agents were detected on the following bark beetles for Europe: Scolytus scolytus, S. triarmatus, S. multistriatus, S. laevis, and on new vectors: Xyleborus dispar and Xyleborinus saxesenii. The spread of Scolytus triarmatus, S. multistriatus and Xyleborinus saxesenii has been remarkable for the last two decades, and S. triarmatus and X. saxesenii are relatively recent newcomers in the northern Baltics. The problem is that the more vectoring beetles there are, the faster spread of Dutch elm disease from tree to tree. Abstract Potential Dutch elm disease vector beetle species were caught with pheromone bottle traps and handpicked in 2019: in total, seven species and 261 specimens were collected. The most common was Scolytus triarmatus, but by percent, the incidence of Ophiostoma novo-ulmi was highest in Scolytus scolytus, followed by Xyleborinus saxesenii and S. triarmatus. We analysed the beetles’ DNA using PacBio sequencing to determine vector beetles of Ophiostoma novo-ulmi. Ophiostoma novo-ulmi was found on six out of seven analysed beetle species: Scolytus scolytus, S. triarmatus, S. multistriatus, S. laevis, Xyleborinus saxesenii and Xyleborus dispar. The last two beetles were detected as vectors for Ophiostoma novo-ulmi for the first time. Previous knowledge on the spread of beetles is discussed.

Purpose: Sleep is an important determinant of health and quality of life. This study aimed to clarify the association between dry eye and sleep quality using a large population-based cohort.Methods: 71,761 participants (19-94 yrs, 59.4% female) from the Lifelines cohort in the Netherlands were assessed for dry eye using the Women's Health Study Dry Eye Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to examine the relationship between poor sleep quality (PSQI score > 5) and dry eye, while correcting for age, sex, BMI, education, income, and 51 possible confounding comorbidities, including autoimmune diseases and psychiatric disorders.Results: Overall, 8.9% of participants had dry eye. Of these, 36.4% had poor sleep quality compared to 24.8% of controls (OR 1.52 (95%CI 1.44-1.60), P < 0.0001, corrected for age and sex). After correcting for all comorbidities, dry eye was still associated with poor sleep (OR 1.20 (95%CI 1.11-1.28), P < 0.0001). This relationship was seen across all ages and sexes. Patients with dry eye scored worse on all subcomponents of the PSQI. Almost one-in-two (44.9%) persons with dry eye symptoms "often" or "constantly" had poor sleep quality. This proportion was similar to participants with sleep apnea and osteoarthritis. Additionally, increasing symptom frequency was tied to increased prevalence of poor sleep quality.Conclusions: All components of sleep quality were significantly reduced in participants with dry eye, even after correcting for comorbidities. These results indicate the substantial impact of dry eye on patients' lives, especially for those with frequent symptoms.

Due to their good material properties (e.g., corrosion and wear resistance, biocompatibility), thermoplastic materials like polyamide 12 (PA12) are interesting for functional coatings on metallic components. To ensure a spatially resolved coating and to shorten the process chain, directed energy deposition of polymer powders by means of a laser beam (DED-LB/P) offers a promising approach. Due to characteristic absorption bands, the use of a thulium fiber laser with a wavelength of 1.94 μm is investigated in a DED-LB/P setup to generate PA12 coatings on stainless steel substrates without the need to add any absorbing additives. The influence of the energy density and powder mass flow was analyzed by infrared thermography. Furthermore, the coatings were characterized by differential scanning calorimetry, laser-scanning-microscopy, optical microscopy and cross-cutting tests. The results in this study demonstrate for the first time the basic feasibility of an absorber-free DED-LB/P process by using a thulium fiber laser. PA12 coatings with a low porosity and good adhesion are achievable. Depending on the application-specific requirements, a trade-off must be made between the density and surface quality of the PA12 coatings. The use of infrared thermography is appropriate for in-situ detection of process instabilities caused by an excessive energy input.

Dry eye disease affects millions of people worldwide, causing pain, vision disturbance, and reduced productivity. Meibomian gland dysfunction, a major cause of dry eye, is characterized by chronic glandular inflammation, thickening of the meibum, obstruction of terminal ducts, and glandular atrophy. Treatment of meibomian gland dysfunction can utilize heat and pressure applied to the meibomian glands, increasing meibum expression. With self-treatments, however, not all patients achieve lasting improvement, and compliance is often low. In-office thermal systems offer a second line of treatment and could be a much-needed addition for patients who do not respond to conventional treatment. We critically evaluated the efficacy and safety of LipiFlow, iLux, and TearCare based on existing literature. While the studies found a single in-office thermal treatment to be safe and effective in improving short-term signs and symptoms in patients with dry eye, long-term efficacy needs to be further evaluated. Thus, well-controlled, long-term efficacy studies are warranted to draw clear conclusions. The treatment seemed to provide rapid relief of symptoms that may last up to 1 year, but at a considerably higher cost than the at-home treatments. The choice of treatment depends on cost, compliance with at-home treatment, and personal preference. This research has been finded by the Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway (TPU) and the US National Institutes of Health Grants R01 EY029789 (DAD) and EY019470 (DAD).

Directed energy deposition (DED) is an additive manufacturing technique that enables rapid production and repair of metallic parts with flexible geometry. The complex nature of thermal and material transport during DED can yield unwanted microstructure heterogeneity, which causes scatter in parts performance. Here, we investigate microstructure variations at different length scales in Inconel 718 produced by powder-blown DED using different deposition rates. We quantify spatial trends in grain structure, texture, composition, and solidification structure within parts and correlate them with variations in hardness, yield strength, and Young's Modulus to highlight the effect of the thermal environment during solidification. We find that the high energy input employed when using high deposition rates is conducive to significant microstructure heterogeneity along both the build and transversal directions, which stems from the asymmetric cooling rates generated by the deposition strategy used. We also find that standard heat treatments employed on Inconel 718 are not suitable to homogenize the microstructure. These results have important implications for the development of industrially relevant build rate strategies for additively manufactured parts. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version This research was funded by the National Research Foundation (NRF) Singapore, under the NRF Fellowship program (NRFNRFF2018–05), and by STE Aerospace Pte. Ltd. YYC and EJ are supported by Nanyang Technological University Singapore (NTU) and the Ministry of Education of Singapore through an Industrial Postgraduate Programme (IPP) scholarship (M4062246) and the collaboration with the University of Strathclyde, UK, respectively.

Directed Energy Deposition (DED) Additive Manufacturing process for metallic parts are becoming increasingly popular and widely accepted due to their potential of fabricating parts of large dimensions. The complex thermal cycles obtained due to the process physics results in accumulation of residual stress and distortion. However, to accurately model metal deposition heat transfer for large parts, numerical model leads to impracticalcomputation time. In this work, a 3D transient finite element model with Quiet/Active element activation is developed for modeling metal deposition heat transfer analysis of DED process. To accurately model moving heat source, Goldak’s double ellipsoid model is implemented with small enough simulation time increment such that laser moves a distance of its radius over the course of each increment. Considering thin build-wall of Stainless Steel 316L fabricated with different process parameters, numerical results obtained with COMSOL 5.6 Multi-Physics software are successfully validated with experiment temperature data recorded at the substrate during the fabrication of 20 layers. To reduce the computation time, elongated ellipsoid heat input model that averages the heat source over its entire path is implemented. It has been found that by taking such large time increments, numerical model gives inaccurate results. Therefore, the track is divided into several sub-tracks, each of which is applied in one simulation increment. In this work, an investigation is done to find out the correct simulation time increment or sub-track size that leads to reduction in computation time (5–10 times) but still yields sufficiently accurate results (below 10% of relative error on temperature). Also, a Correction factor is introduced that further reduces computation error of elongated heat source. Finally, a new correlation is also established in finding out the correct time increment size and correction factor value to reduce the computation time yielding accurate results.

Purpose: The aim of this study was to explore whether prolonged and consistent face mask use might be associated with worsening of dry eye symptoms in patients with dry eye disease (DED). Methods: Subjects with a previous diagnosis of DED. Their OSDI scores were compared with those recorded in Fall 2019 using the Wilcoxon paired test. Participants were stratified by face mask use: heavy (Group A) or standard (Group B) face mask users. Heavy use was defined as wearing any type of face mask for at least 6 hours a day, at least 5 days per week in the last 2 months. Results: 67 subjects (mean age: 45.27 ± 10.06 SD years, 40% males and 60% females). Median OSDI score in Fall 2019: 18.75. Median OSDI in Spring 2020: 20.83. The Hodges-Lehmann median difference was 2.09 (95% CI [1.05, 4.17]) (P < 0.0001). The population was then stratified into heavy and standard face mask users: Group A included heavy users (31 subjects; mean age: 42.81 ± 10.48 SD years; 35% males and 65% females), Group B included standard users (36 subjects; mean age: 47.39 ± 9.31 SD years; 44% males and 56% females). The Hodges-Lehmann median difference was 5.21 (95% CI [3.13, 7.29]) in Group A (P < 0.0001), and 1.04 (95% [0],[ 2.08]) in Group B (P = 0.0177). Conclusion: Prolonged and consistent face mask use is associated with an increase in OSDI scores. Whether face mask use is responsible for the worsening of symptoms of DED remains to be elucidated.

Additive Manufacturing (AM) is a promising technology compared to subtractive processes, in terms of cost or freedom of manufacturing functional parts. Among the AM techniques, Laser Metal Deposition (LMD) and Wire-Arc Additive Manufacturing (WAAM), included in the Direct Energy Deposition (DED) processes, manufacture parts by directly melting the material in a layer-by-layer maner. Those processes are currently mainly operated in open-loop. Thus, an acceptable part regarding the specified specifications is often the result of a trial-and-error method. In order to improve DED processes performances and to get rid of this trial-and-error method, monitoring and numerical simulation are the most widely investigated solutions. These PhD works propose a generic multiphysic monitoring methodology, based on four independant control loops which can be operated simultaneously. Those control loops are dedicated to the part temperature, geometry, and structural health, and the Stick Out. In these PhD works, control loops have been mainly implemented on the WAAM process, and a specific attention has been devoted to their developments to ensure their applicability to the LMD process. Concurrent to these monitoring develoments, an evaluation of some existing numerical tools has been conducted, in order to integrate simulation together with monitoring in a manufacturing environement. This PhD project is part of the Joint Laboratory of Marine Techology formed by Naval Group and Centrale Nantes; La Fabrication Additive métallique apporte de nouvelles possibilités de fabrication et de liberté de conception des pièces fonctionnelles métalliques par rapport aux procédés conventionnels. En particulier, les technologies Direct Energy Deposition (DED), notamment les procédés Laser Metal Deposition (LMD) et Wire-Arc Additive Manufacturing (WAAM) fusionnent directement la matière et la déposent couche par couche pour réaliser une pièce. Actuellement, ces procédés sont majoritairement mis en œuvre en boucle ouverte. Ainsi, l’obtention d’une pièce conforme aux exigences du cahier des charges résulte le plus souvent d’une méthode essai-erreur. Afin d’améliorer la maitrise des procédés DED et de s’affranchir de cette méthode essai-erreur, la simulation numérique et le monitoring sont les principales pistes investiguées dans la littérature. Cette thèse propose une méthodologie générique de monitoring multiphysique, basée sur quatre boucles de contrôle indépendantes et pouvant être mises en œuvre simultanément. Ces boucles de contrôle se focalisent sur la température, la géométrie et la santé matière de la pièce, ainsi que sur le Stick Out. Dans ces travaux, les boucles de contrôle ont été principalement implémentées sur le procédé WAAM. Un soin particulier a été porté sur leur développement pour rendre ces boucles de contrôle adaptables au procédé LMD. Parallèlement à ces travaux, certains outils numériques existants ont été évalués dans l’optique d’être intégrés dans l’environnement de fabrication aux côtés du monitoring. Cette thèse s’inscrit dans le cadre du laboratoire commun Joint Laboratory of Marine Technology regroupant Naval Group et Centrale Nantes

Dry eye disease (DED) is defined by the International Dry Eye Workshop (TFOS DEWS II) as a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.1 In DED patients, activities requiring prolonged gazing with involuntary suppression of blinking can lead to ocular surface irregularities and corneal epithelium damage,2 both affecting visual function3 and eventually preventing patients from performing basic activities of daily life such as reading, driving, or working with screens.4 Consequently, DED negatively impacts quality of life comparable with other severe diseases.5 Recently, the impact of DED on reading speed has been increasingly investigated,6–11 suggesting that reading speed might be substantially affected by the level of corneal staining, especially under straining conditions in daily life such as prolonged duration of reading. The treatment under investigation, CyclASol 0.1%, is a clear topical water-free ophthalmic solution of cyclosporine A in a novel vehicle, the semifluorinated alkane (SFA)-based EyeSol technology, using the SFA perfluorobutylpentane (abbreviated F4H5). This topical formulation was developed for the treatment of DED with the goal of increasing local bioavailability, avoiding the use of oils, surfactants, and preservatives. Cyclosporine A is an antiinflammatory agent with immunomodulatory properties with proven efficacy in DED.12 Potential benefits of the CyclASol 0.1% formulation in a water-free SFA solution include improved tolerability and decreased visual disturbance compared with typical cyclosporine A formulations, which frequently involve surfactants and oils. A further potential benefit is an improved clinical efficacy because of better local bioavailability. CyclASol has been investigated previously in one phase 1 clinical study with healthy volunteers and one phase 2 clinical study in patients with DED. Both clinical studies showed an excellent tolerability and safety profile. The CyclASol phase 2 study was a randomized, double-masked, vehicle-controlled, dose finding study with CyclASol 0.05% and CyclASol 0.1% and an open-label active comparator and showed a consistent reduction in corneal and conjunctival staining after treatment with CyclASol compared with the vehicle and with the active comparator, with an early onset of effect as of week 2.13 The central area of the cornea, which is an important region relevant to visual function, benefitted most. Thus, reading assessments were included in the present phase 2B/3 study. The treatment effect on cornea staining parameters was more pronounced in patients with higher baseline values of total corneal fluorescein staining (CFS). Therefore, patients with total CFS scores ≥10 [National Eye Institute (NEI) scale] at baseline were chosen for the confirmatory clinical phase 2B/3 study. The 0.1% concentration was selected for its trend toward a better effect on symptoms in the target population. This work presents the results of the phase 2B/3 study CYS-003 (ESSENCE) designed to confirm the efficacy, safety, and tolerability of CyclASol 0.1% ophthalmic solution in comparison with its vehicle (F4H5) for the treatment of signs and symptoms of DED.

Mike Taylor,1 George Ousler,2 Gail Torkildsen,3 Claire Walshe,1 Matthew C T Fyfe,1 Adele Rowley,1 Steve Webber,1 John D Sheppard,4 Ajay Duggal1 1TopiVert Pharma Limited, London, UK; 2Ora Inc., Andover, MA, USA; 3Andover Eye Associates, Andover, MA, USA; 4Virginia Eye Consultants, Norfolk, VA, USA Purpose: To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).Patients and methods: A randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to severe DED population included >6 months DED history; OSDI© score ≥18; Schirmer’s test score ≤10 and ≥1 mm/5 minutes; tear film break-up time >1 and

John L Bradley,1,2 Ipek Özer Stillman,3 Irina Pivneva,4 Annie Guerin,4 Amber M Evans,5 Reza Dana6 1Naval Medical Research Unit Dayton, Vision Science Lab, Wright Patterson AFB, OH, USA; 2University of Pikeville, Kentucky College of Optometry, Pikeville, KY, USA; 3Takeda, Lexington, MA, USA; 4Analysis Group, Inc, Montreal, QC, Canada; 5Health ResearchTx LLC, Trevose, PA, USA; 6Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA Objectives: Dry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care. Methods: In this population-based study using the US Department of Defense Military Health System claims database of >9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003–2015) and annual incidence (2008–2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions. Results: In 2003–2015, the most common ocular conditions were disorders of refraction and accommodation (25.84%), cataracts (17.14%), glaucoma (7.27%), disorders of the conjunctiva (6.76%), other retinal disorders (5.94%), and DED (5.28%). DED was the fifth most prevalent ocular condition in women (7.78%) and ninth most prevalent in men (2.96%). In 2012, DED had the third highest annual incidence (0.87%), behind disorders of refraction/accommodation (1.87%) and cataracts (1.50%). Conclusion: This study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment. Keywords: DED, epidemiology, prevalence, incidence

John L Bradley,1,2 Ipek Özer Stillman,3 Irina Pivneva,4 Annie Guerin,4 Amber M Evans,5 Reza Dana6 1Naval Medical Research Unit Dayton, Vision Science Lab, Wright Patterson AFB, OH, USA; 2University of Pikeville, Kentucky College of Optometry, Pikeville, KY, USA; 3Takeda, Lexington, MA, USA; 4Analysis Group, Inc, Montreal, QC, Canada; 5Health ResearchTx LLC, Trevose, PA, USA; 6Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA Objectives: Dry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care. Methods: In this population-based study using the US Department of Defense Military Health System claims database of >9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003–2015) and annual incidence (2008–2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions. Results: In 2003–2015, the most common ocular conditions were disorders of refraction and accommodation (25.84%), cataracts (17.14%), glaucoma (7.27%), disorders of the conjunctiva (6.76%), other retinal disorders (5.94%), and DED (5.28%). DED was the fifth most prevalent ocular condition in women (7.78%) and ninth most prevalent in men (2.96%). In 2012, DED had the third highest annual incidence (0.87%), behind disorders of refraction/accommodation (1.87%) and cataracts (1.50%). Conclusion: This study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment. Keywords: DED, epidemiology, prevalence, incidence

Green laser sources are advantageous in the processing of copper due to the increase of absorptivity compared with more commonly available infrared lasers. Laser metal deposition of copper with a green laser onto various substrate metals namely copper, aluminium, steel and titanium alloy was carried out and observed through high-speed imaging. The effects of process parameters such as laser power, cladding speed and powder feed rate, and material attributes such as absorptivity, surface conditions and thermal conductivity are tied together to explain the size and geometry of the melt pool as well as the fraction of the power used for melting material. The copper substrate has the smallest melt pool with a high angle, followed by aluminium, steel and titanium alloy. The incorporation times for powder grains in the melt pools vary based on the substrate materials. Its dependency on material properties, including surface tension forces, melting temperatures and material density, is discussed. Oxide skins present on melt pools can affect powder incorporation, most significantly on the aluminium substrate. The lower limits of the fraction of power irradiated on the surface used purely for melting were calculated to be 0.73%, 2.94%, 5.95% and 9.78% for the copper, aluminium, steel and titanium alloy substrates, respectively, showing a strong dependence on thermal conductivity of the substrate material. For a copper wall built, the fraction was 2.66%, much higher than a single clad on a copper substrate, due to reduced workpiece heating. The results of this paper can be transferred to other metals with low absorptivity such as gold.

Additive Manufacturing (AM) provides the possibility to produce complex part geometries on a layer-by-layer basis. In AM processes, a heat source moves over the part to either deposit powder or wire feedstock or to melt thin powder layers that are spread onto a powder bed. The moving heat source inevitably creates an inhomogeneous temperature distribution, which affects the residual stresses, part distortion, and local mechanical properties. Accumulation of heat in corners and path intersections may result in overheating and hence defects. In this study, a method for improving the temperature distribution in direct energy deposition processes is presented. FEM simulations in LS Dyna are coupled to MATLAB in order to divide a basic AM-FEM model and to adjust the model rule-based during the calculation. With this Rule-Based Path Identification (RBPI), the temperature history is used to choose the position of the next bead. With one bead wide wall, a temperature improvement of 90°C could be achieved. The new simulation method is adopted for a delay time between the beads for 10s. In conclusion, it is shown that the RBPD helps to reduce the inhomogeneous temperature distribution for a metal printing process without expensive optimization., Procedia Manufacturing, 47, ISSN:2351-9789, 23rd International Conference on Material Forming

Additive manufacturing is a technology that enables the repair and coating of high-added-value parts. In applications such as hot stamping, the thermal behavior of the material is essential to ensure the proper operation of the manufactured part. Therefore, the effective thermal diffusivity of the material needs to be evaluated. In the present work, the thermal diffusivity of laser-deposited AISI H13 is measured experimentally using flash and lock-in thermography. Because of the fast cooling rate that characterizes the additive process and the associated grain refinement, the effective thermal diffusivity of the laser-deposited AISI H13 is approximately 15% lower than the reference value of the cast AISI H13. Despite the directional nature of the process, the laser-deposited material&rsquo, s thermal diffusivity behavior is found to be isotropic. The paper also presents a case study that illustrates the impact of considering the effective thermal conductivity of the deposited material on the hot stamping process.

Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2020; Aachen 1 Online-Ressource (xiv, 125 Seiten) : Illustrationen, Diagramme (2020). = Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2020, Laser additive manufacturing (LAM) involves layer-by-layer production of components based on a computer-aided design file (CAD) by repetitive melting of metallic powder with a focused laser beam. The inherent geometrical freedom of this technique enables the production of complex and highly customized components. However, post-processing, including heat treatment, of these components remains critical with problems associated with cracking or non-uniform quenching. The layer-by-layer manufacturing process results in a peak-like time-temperature profile experienced during LAM. This intrinsic heat treatment (IHT) can trigger precipitation reactions in certain alloys. There is potential in exploiting IHT to achieve desired microstructure and mechanical properties, hence, removing the need for post-process heat treatment. This in-process heat treatment approach would be similar to current industrial practices, for example, thermomechanical treatment. Utilization of IHT to achieve desired microstructures and mechanical properties requires a fundamental understanding of the precipitation progress during IHT and development of adapted alloys and process parameters. This work aims at identifying important features of the IHT and develop a fundamental understanding of how these affect the precipitation progress. Simple, model Al-Sc alloys were selected for this study based on the fast precipitation kinetics and availability of CALPHAD databases. Use of high purity (>99 wt.%) Al alloys presented the first challenge in this work, as high conductivity metals are considered difficult to process in LAM. A predictive process parameters optimization routine was developed using analytical models to predict the melt pool depth and statistical design of experiments techniques. The predictive approach was further expanded for use in in-situ alloying during LAM using mixtures of elemental powders. After suitable process parameters for processing of the model alloys were identified, thin-walled structures were made by depositing single tracks on top of one another using directed energy deposition (DED), a type of LAM technique. Manufacturing of thin-walled samples allowed achieving different cooling rates within a single sample. Si, which has a three-fold effect in promoting precipitation: higher driving force, lower interface energy, and higher diffusivity, was used to trigger IHT induced precipitation in the model Al-Sc alloys. Process parameters were modified to be able to reach ~90% of the peak hardness for the model alloy without the need for any post-process ageing treatment. Additional samples were produced using laser powder bed fusion (LPBF), another LAM technique. Higher cooling rates are achieved during LPBF as compared to DED, preventing any IHT induced precipitation during LPBF processing. The samples were isothermally heat-treated at different temperatures and the precipitation progress was experimentally measured using in-situ small-angle X-ray scattering (SAXS) and ex-situ atom probe tomography (APT). The experimental measurements were used to develop a Kampmann-Wagner based precipitate model. Application of the precipitation model to peak-like time-temperature profiles gave important insights on the effect of various aspects of IHT on the in-process precipitation progress during LAM processing. This thesis shows the tremendous potential of using IHT during LAM processes as a replacement for post-process ageing heat treatments and presents the alloy and process design approaches which can be used to advance the precipitation progress during IHT., Published by Aachen

This thesis looks into the creation of the Takamanda National Park in South West Cameroon from 1929. In particular this thesis looks at the evolution of discourse around participation and how documents take a role of their own in the creation of the park.

The Directed Energy Deposition (DED) process of metals, has a broad range of applications in several industrial sectors. Surface modification, component repairing, production of functionally graded materials and more importantly, manufacturing of complex geometries are major DED’s applications. In this work, a multi-physics numerical model of the DED process of maraging steel is developed to study the influence of the powder stream specifications on the melt pool’s thermal and fluid dynamics conditions. The model is developed based on the Finite Volume Method (FVM) framework using the commercial software package Flow-3D. Different physical phenomena e.g. solidification, evaporation, the Marangoni effect and the recoil pressure are included in the model. As a new feature, the powder particles’ dynamics are modeled using a Lagrangian framework and their impact on the melt pool conditions is taken into account as well. In-situ and ex-situ experiments are carried out using a thermal camera and optical microscopy. The predicted track morphology is in good agreement with the experimental measurements. Besides, the predicted melt pool evolution follows the same trend as observed with the online thermal camera. Furthermore, a parametric study is carried out to investigate the effect of the powder particles incoming velocity on the track morphology. It is shown that the height-to-width ratio of tracks increases while using higher powder velocities. Moreover, it is shown that by tripling the powder particles velocity, the height-to-width ratio increases by 104% and the wettability of the track decreases by 24%.

Mike Taylor,1 George Ousler,2 Gail Torkildsen,3 Claire Walshe,1 Matthew C T Fyfe,1 Adele Rowley,1 Steve Webber,1 John D Sheppard,4 Ajay Duggal1 1TopiVert Pharma Limited, London, UK; 2Ora Inc., Andover, MA, USA; 3Andover Eye Associates, Andover, MA, USA; 4Virginia Eye Consultants, Norfolk, VA, USA Purpose: To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).Patients and methods: A randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to severe DED population included >6 months DED history; OSDI© score ≥18; Schirmer’s test score ≤10 and ≥1 mm/5 minutes; tear film break-up time >1 and

A multi-component and multi-phase-field modelling approach, combined with transformation kinetics modelling, was used to model microstructure evolution during laser metal powder directed energy deposition of Alloy 718 and subsequent heat treatments. Experimental temperature measurements were utilised to predict microstructural evolution during successive addition of layers. Segregation of alloying elements as well as formation of Laves and delta phase was specifically modelled. The predicted elemental concentrations were then used in transformation kinetics to estimate changes in Continuous Cooling Transformation (CCT) and Time Temperature Transformation (TTT) diagrams for Alloy 718. Modelling results showed good agreement with experimentally observed phase evolution within the microstructure. The results indicate that the approach can be a valuable tool, both for improving process understanding and for process development including subsequent heat treatment. Funding Agencies|European Regional Development Fund; KK Foundation (Stiftelsen for Kunskaps- och Kompetensutveckling)

Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer. [BMB Reports 2016; 49(3): 159-166].

Contemporary quantitative mass spectrometry provides fascinating opportunities in defining the stoichiometry of high-molecular weight complexes or multiprotein platforms. The composition stoichiometry of multiprotein platforms is a key to understand the regulation of complex signaling pathways and provides a basis for constructing models in systems biology. Here we present an improved AQUA technique workflow that we adapted for the quantitative mass spectrometry analysis of the stoichiometry of the CD95 (Fas/APO-1) death inducing signaling complex (DISC). The DISC is a high-molecular weight platform essential for the initiation of CD95-mediated apoptotic and non-apoptotic responses. For protein quantification, CD95 DISCs were immunoprecipitated and proteins in the immunoprecipitations were separated by one-dimensional gel electrophoresis, followed by protein quantification using the AQUA technique. We will discuss in detail AQUA analysis of the CD95 DISC focusing on the key issues of this methodology, i.e., selection and validation of AQUA peptides. The application of this powerful method allowed getting new insights into mechanisms of procaspase-8 activation at the DISC and apoptosis initiation [1]. Here we discuss the AQUA methodology adapted by us for the analysis of the CD95 DISC in more detail. This approach paves the way for the successful quantification of multiprotein complexes and thereby delineating the intrinsic details of molecular interactions.