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Summary Research in low Earth orbit (LEO) has become more accessible. The 2020 Biomanufacturing in Space Symposium reviewed space-based regenerative medicine research and discussed leveraging LEO to advance biomanufacturing for regenerative medicine applications. The symposium identified areas where financial investments could stimulate advancements overcoming technical barriers. Opportunities in disease modeling, stem-cell-derived products, and biofabrication were highlighted. The symposium will initiate a roadmap to a sustainable market for regenerative medicine biomanufacturing in space. This perspective summarizes the 2020 Biomanufacturing in Space Symposium, highlights key biomanufacturing opportunities in LEO, and lays the framework for a roadmap to regenerative medicine biomanufacturing in space., Sharma and colleagues recap the 2020 Biomanufacturing in Space Symposium, which reviewed space-based regenerative medicine research and discussed opportunities to leverage low Earth orbit (LEO) to advance biomanufacturing for regenerative medicine. This perspective will highlight key biomanufacturing opportunities in LEO, note current technical gaps, and discuss next steps in developing a roadmap to biomanufacturing in space for regenerative medicine applications.

Straightforward manufacturing pathways toward large-scale, uniformly layered composites may enable the next generation of materials with advanced optical, thermal, and mechanical properties. Reaction–diffusion systems are attractive candidates to this aim, but while layered composites theoretically could spontaneously arise from reaction–diffusion, in practice randomly oriented patches separated by defects form, yielding nonuniformly patterned materials. A propagating reaction front can prevent such nonuniform patterning, as is the case for Liesegang processes, in which diffusion drives a reaction front to produce layered precipitation patterns. However, while diffusion is crucial to control patterning, it slows down transport of reactants to the front and results in a steady increase of the band spacing as the front advances. Here, we circumvent these diffusive limitations by embedding the Liesegang process in mechanically responsive hydrogels. The coupling between a moving reaction front and hydrogel contraction induces the formation of a self-regulated transport channel that ballistically carries reactants toward the area where patterning occurs. This ensures rapid and uniform patterning. Specifically, large-scale ( > 5-cm) uniform banding patterns are produced with tunable band distance ( d = 60 to 160 µm) of silver dichromate crystals inside responsive gelatin–alginate hydrogels. The generality and applicability of our mechanoreaction–diffusion strategy are demonstrated by forming patterns of precipitates in significantly smaller microscopic banding patterns ( d = 10 to 30 µm) that act as self-organized diffraction gratings. By circumventing the inherent limitations of diffusion, our strategy unlocks the potential of reaction–diffusion processes for the manufacturing of uniformly layered materials.

This study aims to assess the viability of waste tire chips as sand reinforcement for enhancing the performance of shallow foundations. Detailed experimental investigation is carried out to analyze the behavior of model footing placed on sand reinforced with waste tire chips, and the observed improvement is quantified in terms of a non-dimensional factor, bearing capacity ratio (BCR). The influence of variation of several factors such as the content of tire-chip reinforcement, the extent of tire reinforced sand zone, footing shape, the effect of submergence, and scale effects on BCR has also been studied. Test results indicate significant improvement in BCR validating the effectiveness of tire chips in improving the bearing capacity of sand. The optimum tire content, depth of reinforced zone, and width of the reinforced zone are recommended as 30%, 1B-2B, and 3B-5B, respectively (B is the width of the footing), where BCR increased to more than 5 under both low strain and high strain conditions. It was also established that submergence of the reinforced soil and shape and size of footing did not have a significant influence on the BCR. Moreover, the performance of tire chip-reinforced sand is found to be better than both fiber- and geogrid-reinforced sand. Bearing capacity increase of up to 1.89 times and 2.40 times was observed in tire chip-reinforced sand in comparison to fiber- and geogrid-reinforced sand, respectively. On the whole, the significant improvement in BCR and the better performance of tire chips over other alternatives ascertain that bulk utilization of tire wastes in shallow foundations has immense potential for effective waste management of large stockpiles of tires and can prove to be an economical and sustainable solution for the construction industry.

The development of intelligent packaging based on natural and biodegradable resources is getting more attention by researchers in recent years. The aim of this study was to develop and characterize a pH-sensitive films based on sago starch and incorporated with anthocyanin from torch ginger. The pH-sensitive films were fabricated by casting method with incorporation of different torch ginger extract (TGE) concentration. The surface morphology, physicochemical, barrier, and mechanical properties as well as the pH-sensitivity of films were investigated. The film with the highest concentration of TGE showed the lowest tensile strength (4.26 N/m2), toughness (2.54 MJ/m3), Young's modulus (73.96 MPa) and water vapour permeability (2.6 × 10−4 g·m/day·kPa·m2). However, its elongation at break (85.14%), moisture content (0.27%) and water solubility (37.92%) were the highest compared to other films. pH sensitivity analysis showed that the films containing TGE extract, changes in colour by changing the pH. The colour of films changed from pink to slightly green as the pH increased from pH 4 to 9. Thus, the developed pH-sensitive film with torch ginger extract has potential as intelligent packaging for detection of food freshness or spoilage to ensure their quality and safe consumption.

The aim of this work was to develop new method for the production of chitosan/agarose (CHN/A) film that could serve as a potential artificial skin substitute for regenerative medicine applications. Within this new production method, the concentrations of biomaterial components (chitosan in CH3COOH and agarose in NaOH) were optimized to provide neutralization of the resultant mixture up to pH approx. 6.0 without uncontrolled precipitation (gelation) of chitosan constituent. Produced thin film was subjected to comprehensive evaluation of its biomedical potential by determination of mechanical, physicochemical, and biological properties. It was demonstrated that the developed CHN/A film reveals slightly acidic pH of 5.98 known to support skin regeneration, high exudate absorption capacity, and is prone to biodegradation in simulated enzymatic wound environment. Performed tensile test proved high elastic deformations of the film (Young's modulus = 0.02 MPa, elongation at break = 23%) in a wet state, which would allow suitable stretching after application at the wound site. Moreover, novel biomaterial is non-toxic and supports fibroblast growth on its surface. Based on the obtained results it may be concluded that the produced CHN/A film possesses all necessary features of the artificial skin substitute.

The aim of this study was to develop a zein/potato starch (PS) film based on chitosan nanoparticles incorporated with curcumin (CCN). The CCN film was characterized for encapsulation efficiency, particle size, zeta potential, polydispersity index (PDI), relative release, and DPPH radical scavenging test. Our results showed that the CCN encapsulated effectively curcumin (CUR) (84.8% ± 1.1%) and presented with high oxidation resistance and relative release efficiency. The CCN/zein/PS composite films were round, smooth, and compact. We measured and compared the mechanical properties, oxygen permeability (OP), water vapor permeability (WVP), relative release efficiency, and DPPH radical scavenging properties of the composite films of different mass ratios. We observed that the composite film had good mechanical and barrier properties. Further, we evaluated the preservative efficacy of the composite film on Schizothorax prenati fillets by measuring pH, total volatile basic nitrogen (TVB-N), thiobarbituric acid-reactive substances (TBARS), hardness, microbial counts, organoleptic characteristics, and other fillet quality parameters. The CCN/zein/PS composite film delayed physicochemical changes in the Schizothorax prenati fillets and prolonged their shelf life by up to 15 days. In conclusion, our work shows that CCN/zein/PS composite film holds promise as a potential bioactive packaging material for Schizothorax prenati fillets.

The interaction between the terahertz wave propagating in free space and the sample is weak, which leads to the weak signal of the sample, which cannot meet the detection needs of trace samples. In order to meet the detection of trace samples, a kind of metamaterial absorber (the basic unit of the absorber is composed of gold-high resistance silicon-aluminum three-layer structure) is designed, and the monolayer graphene is transferred on the surface of the metamaterial absorber to construct the graphene-metamaterial absorber heterostructure. The transmission spectrum of the resonant cavity is simulated and measured by terahertz time domain spectroscopy system, and the obvious resonance frequency shift is observed. The results show that the graphene-metamaterial absorber heterostructure can detect josamycin antibiotic solution with concentration of 0.02 mg/L (the mass of josamycin is 0.2 ng). Compared with using the same structure metamaterial absorber to detect josamycin antibiotics, the sensitivity is increased by an order of magnitude. Using graphene-metamaterial heterostructure to detect the relative change of heterostructure reflectivity caused by josamycin antibiotics can reach 40%. The research in this paper provides a new technical means for accurate and rapid detection in terahertz band.

ObjectivesThe popularity of high silica content artificial stone has been associated with emergence of severe, progressive silicosis as a major health issue affecting workers in the stone benchtop industry. This population-based health assessment programme has been implemented with the aim of identifcation of silica-associated disease at a preclinical stage.MethodsAll current and former workers from the stone benchtop industry in the State of Victoria are offered free health assessments. Primary evaluations include a standardised questionnaire, physical examination, spirometry and gas transfer assessment and International Labour Organisation-categorised chest X-ray. Secondary evaluations include high-resolution CT chest, blood tests and a respiratory physician evaluation.ResultsAt the end of the first 12 months, 86/239 (36%) workers who had completed secondary evaluation were diagnosed with silicosis (65 simple silicosis and 21 complicated silicosis). 22 had worked in the industry for less than 10 years at the time of diagnosis. Of those with simple silicosis, 80% of workers reported breathlessness only with strenuous exercise (modified Medical Research Council score of 0), and lung function was well preserved (prebronchodilator forced vital capacity mean 99.8% predicted (SD 13.6), diffusion capacity of the lung for carbon monoxide mean 96.2% predicted (SD 18.0)). Antinuclear antibodies were detected in 37% with silicosis and 24% without silicosis.ConclusionEarly results from this comprehensive health assessment programme have indicated a high proportion of referred artificial stone benchtop workers have silicosis, including many with early-stage disease. The common finding of antinuclear antibodies suggest significant potential for autoimmune disease in this occupational group.

Coal mine lung dust disease (CMDLD) and artificial stone (AS) silicosis are preventable diseases which have occurred in serious outbreaks in Australia recently. This has prompted a TSANZ review of Australia's approach to respiratory periodic health surveillance. While regulating respirable dust exposure remains the foundation of primary and secondary prevention, identification of workers with early disease assists with control of further exposure, and with the aims of preserving lung function and decreasing respiratory morbidity in those affected. Prompt detection of an abnormality also allows for ongoing respiratory specialist clinical management. This review outlines a medical framework for improvements in respiratory surveillance to detect CMDLD and AS silicosis in Australia. This includes appropriate referral, improved data collection and interpretation, enhanced surveillance, the establishment of a nationwide Occupational Lung Disease Registry and an independent advisory group. These measures are designed to improve health outcomes for workers in the coal mining, AS and other dust‐exposed and mining industries.

Background Exposure to toner, a substance used in photocopiers and printers, has been associated with siderosilicosis and other adverse effects. However, these findings are limited, and there is insufficient evidence on the long-term effects of toner exposure. Using longitudinal analysis, this study aimed to examine the effects of work involving toner exposure on the respiratory system over time. Methods We conducted a prospective cohort study in a Japanese toner and copier manufacturing enterprise between 2003 and 2013. The cohort included a total of 1468 workers, which comprised 887 toner-handling workers and 581 non-toner-handling workers. We subdivided the toner-handling workers into two groups according to the toner exposure concentration, based on the baseline survey in 2003. We compared the chest X-ray results, respiratory function indicators, and serum and urinary biomarkers of inflammation, allergy, and oxidative stress among the three groups: high-concentration toner exposure group, low-concentration toner exposure group, and non-toner-handling group. To consider the effects of individual differences on the longitudinal data, we used a linear mixed model. Results Similar chest X-ray results, the biomarkers, and most of the respiratory function indicators were found in the non-toner-handling and toner-handling groups. There were no significant yearly changes in the percentage of vital capacity (%VC) in the high-concentration toner exposure group, while there was a significant yearly increase in %VC in the low-concentration toner exposure group and non-toner-handling group. The yearly change in each group was as follows: high-concentration toner exposure group, − 0.11% (95% confidence interval [CI], − 0.29 to 0.08; P = 0.250); low-concentration toner exposure group, 0.13% (95% CI, 0.09–0.17; P Conclusions In our 10-year prospective study, toner-handling work was not associated with the deterioration of respiratory function and an increase in biomarker values for inflammation, allergy, and oxidative stress. This finding suggests that toner-handling work is irrelevant to the onset of respiratory disease and has minimal adverse effects on the respiratory system under a well-managed work environment.

Aims Develop an effective laboratory method to consistently recover viral loads from porous concrete coupons sufficient for disinfectant efficacy testing. Investigate the role of concrete matrix pH on the recovery of foot-and-mouth disease virus (FMDV) and African Swine Fever virus (ASFV) from porous concrete. Compare parameters off FMDV and ASFV inactivation on porous and nonporous surfaces in quantitative carrier tests of a liquid chemical disinfectant. Methods and results Concrete test coupons were fabricated from commercial and industrial sources and carbonated by exposure to 5% CO2 in a humidified incubator, lowering the matrix pH. Neither dried FMDV nor ASFV were recovered from high-pH concrete control coupons. Recovery of infectious virus from lower pH carbonated concrete was similar to stainless steel coupon controls. Exposure to the liquid disinfectant Virkon™ S inactivated FMDV and ASFV on porous concrete. Conclusions Concrete matrix pH had a greater impact than surface porosity on the ability to recover viable virus from unsealed concrete. Significance and Impact of the Study Concrete is commonly found in environments where virus decontamination is required. This study demonstrates a reproducible method to recover sufficient viral loads from porous concrete coupons to facilitate quantitative carrier testing. This method provides a basis for evidence-based validation testing of chemical disinfectants to inactivate pH-sensitive viruses on unsealed concrete.

Purpose: To evaluate glistening and long-term stability of five commercially available intraocular lenses. Methods: This experimental study evaluated the SN60WF (Alcon), XY1 (Hoya), NS-60YG (NIDEK), ZCB00V (Johnson & Johnson Vision) and AN6KA (Kowa) intraocular lenses. To generate glistenings, intraocular lenses were immersed in physiological saline at 50°C for 2 h, then left in situ at 35°C and removed at regular intervals over 24 h. Stability of the intraocular lens material was assessed by immersing intraocular lenses into vials of purified water placed at 100°C for 115 days, which simulated 20-year ageing. Gas chromatography–mass spectrometry was used to detect leached compounds. Results: Almost no glistenings were observed for the AN6KA. Glistenings were observed in the remaining intraocular lenses after 3 h. The number of glistenings gradually disappeared by 6 h for all intraocular lenses except SN60WF (12 h). Only the NS-60YG and ZCB00V intraocular lenses had no changes in weight or dimensions. Gas chromatography–mass spectrometry detected phenethyl alcohol in XY1 and SN60WF, 2-phenoxyethanol in AN6K and no compounds in the remaining intraocular lenses. A peak shift due to the carbonyl group between 1600 and 1700 cm−1 was detected for the SN60WF and AN6K intraocular lenses only. Conclusion: SN60WF had the most numerous glistenings that resolved over a longer duration. The long-term stability test confirmed elution of the intraocular lens material–derived compounds and signs of degradation for the XY1, SN60WF and AN6K intraocular lenses. NS-60YG and ZCB00V showed no signs of deterioration due to ageing. Differing manufacturing methods likely play a role in the stability of intraocular lenses.

Ancillary materials (AMs) play a critical role in the manufacture of cell and gene therapies, and best practices for their quality management are the subject of ongoing discussion. Given that the final product cannot be sterilized, AM quality becomes increasingly critical to the clinical advancement of cell and gene therapies. Despite a lack of direct legislative direction regarding AM quality, internationally harmonized guidance is available from several industry-standard bodies that describe the principles and application of a risk-based approach to AM qualification and related supply-chain risk management. According to a best-practice risk-based approach, AMs must be adequately qualified to a degree that reflects the level of risk the material presents to patient safety and the drug product's specification. This general approach can be implemented in different ways, and balancing quality with cost of goods is critical to the cost-effective manufacture of advanced therapy medicinal products. In some cases, it may be preferable or necessary to use AMs that are produced in compliance with current Good Manufacturing Practice. However, developers may be able to suppress manufacturing costs without undermining safety or regulatory compliance in the case that a material presents a lower risk profile. Despite a great deal of attention and interest in the quality of AMs in the cell and gene therapy space, there is still a need for greater harmonization to create a shared understanding of what constitutes a risk-based approach to AM production and sourcing. In this article, we propose a staged approach to AM quality that achieves a balance between the competing demands of risk mitigation and cost of goods containment at the various stages of AM quality development. Our novel, heuristic framework for communication among AM suppliers, users and regulators aims to bring down development and manufacturing costs and lessen the workload around regulatory compliance.

Regulatory T cells (Tregs) are a promising therapy for several immune-mediated conditions but manufacturing a homogeneous and consistent product, especially one that includes cryopreservation, has been challenging. Discarded pediatric thymuses are an excellent source of therapeutic Tregs with advantages including cell quantity, homogeneity and stability. Here we report systematic testing of activation reagents, cell culture media, restimulation timing, and cryopreservation to develop a good-manufacturing-practice (GMP)-compatible method to expand and cryopreserve Tregs. By comparing activation reagents, including soluble antibody tetramers, antibody-conjugated beads and artificial antigen-presenting cells (aAPCs), and different media, we found that the combination of Dynabeads Treg Xpander and ImmunoCult-XF medium preserved FOXP3 expression and suppressive function, and resulted in expansion that was comparable to a single stimulation with aAPCs. Cryopreservation tests revealed a critical timing effect: only cells cryopreserved 1–3 days, but not >3 days, after restimulation maintained high viability and FOXP3 expression upon thawing. Restimulation timing was a less critical process parameter than the time between restimulation and cryopreservation. This systematic testing of key variables provides increased certainty regarding methods for in vitro expansion and cryopreservation of Tregs. The ability to cryopreserve expanded Tregs will have broad-ranging applications including enabling centralized manufacturing and long-term storage of cell products.

Humanity has become a dominant force in shaping the face of Earth1–9. An emerging question is how the overall material output of human activities compares to the overall natural biomass. Here we quantify the human-made mass, referred to as ‘anthropogenic mass’, and compare it to the overall living biomass on Earth, which currently equals approximately 1.1 teratonnes10,11. We find that Earth is exactly at the crossover point; in the year 2020 (± 6), the anthropogenic mass, which has recently doubled roughly every 20 years, will surpass all global living biomass. On average, for each person on the globe, anthropogenic mass equal to more than his or her bodyweight is produced every week. This quantification of the human enterprise gives a mass-based quantitative and symbolic characterization of the human-induced epoch of the Anthropocene. Estimates of global total biomass (the mass of all living things) and anthopogenic mass (the mass embedded in inanimate objects made by humans) over time show that we are roughly at the timepoint when anthropogenic mass exceeds total biomass.

The aim of this study was to characterize the performance of polylactic acid (PLA) material when manufactured by melt deposition modeling (FDM) technology. For the elaboration and organization of the experimental procedure, this study was constructed in accordance with the ASTM D3039/3039-95A standard, using a total of 36 specimens, modeled using Autodesk Inventor CAD software and later exported to CAM software Makerware, where parameters and processes for 3D printing were defined. The tensile tests were carried out on the EMIC DL 3000 machine, maintaining a standard condition with the laboratory at a temperature around 20°C. The values ​​defined as significant for this study were: Maximum Tension; Breaking Stress and Modulus of Elasticity. The manufactured specimens showed anisotropic behavior. In the stress-strain tests, the ruptures occurred in perfect profile rupture. The stress-strain curves showed practically no yield area. The deposition rates of 100% for the X axis showed higher rates for tensile strength as opposed to the 20% deposition rates for the Y axis. With regard to elongation, the parts with 20% deposition rate on the X axis had higher rates. Mechanical properties, tensile strength and flexural strength, increased with filling. PLA, manufactured using the FDM process, demonstrated better mechanical performance when produced on an X axis with 100% deposition rates for the structural internal fill and an extrusion temperature of 200°C. It is characterized as a typical polymeric brittle. El objetivo de este estudio fue caracterizar el rendimiento del material de ácido poliláctico (PLA) cuando se fabrica mediante la tecnología de modelado de deposición por fusión (FDM). Para la preparación y organización del procedimiento experimental, este estudio se construyó de acuerdo con la norma ASTM D3039 / 3039-95A, utilizando un total de 36 probetas, modeladas con el software Autodesk Inventor CAD y posteriormente exportadas al software CAM Makerware, donde parámetros y Se definieron los procesos para la impresión 3D. Se realizaron ensayos de tracción en la máquina EMIC DL 3000, manteniendo una condición estándar con el laboratorio a una temperatura en torno a los 20 ° C. Los valores definidos como significativos para este estudio fueron: Voltaje Máximo; Esfuerzo de rotura y módulo de elasticidad. Las probetas fabricadas mostraron un comportamiento anisotrópico. En las pruebas de tensión-deformación, las roturas se produjeron en perfecta rotura de perfil. Las curvas de tensión-deformación no mostraron prácticamente ningún área de fluencia. Las tasas de deposición del 100% para el eje X mostraron tasas más altas de resistencia a la tracción en comparación con las tasas de deposición del 20% para el eje Y. Con respecto al alargamiento, las piezas con una tasa de deposición del 20% en el eje X tenían tasas más altas. Propiedades mecánicas, resistencia a la tracción y resistencia a la flexión, aumentadas con el relleno. El PLA, fabricado mediante el proceso FDM, demostró un mejor rendimiento mecánico cuando se produjo en un eje X con tasas de deposición del 100% para el relleno interno estructural y una temperatura de extrusión de 200 ° C. Se caracteriza por ser un frágil polimérico típico. O objetivo deste estudo foi caracterizar a performance do material poli ácido lático (PLA) quando manufaturado pela tecnologia modelagem por fusão e deposição (FDM). Para a elaboração e organização do procedimento experimental, este estudo foi construído de acordo com a norma ASTM D3039/3039-95A, utilizando um total de 36 corpos de prova, modelados através do software CAD Autodesk Inventor e, posteriormente, exportados para o software CAM Makerware, onde definiu-se os parâmetros e processos para a impressão 3D. Os ensaios de tração foram realizados na máquina EMIC DL 3000, mantendo uma condição padrão com o laboratório a uma temperatura em torno de 20°C. Os valores definidos como significativos para este estudo foram: Tensão Máxima; Tensão de Ruptura e Módulo de Elasticidade. Os corpos de prova manufaturados apresentaram comportamento anisotrópico. Nos testes de tensão-deformação, as rupturas ocorreram em perfeito rompimento de perfil. As curvas tensão-deformação apresentaram-se praticamente sem área de escoamento. As taxas de deposição de 100% para o eixo X demonstraram maiores índices para tensão de ruptura em contraposto as taxas de deposição de 20% do eixo Y. No que se refere ao alongamento, as peças com 20% de taxa de deposição no eixo X apresentaram maiores índices. As propriedades mecânicas, resistência à tração e resistência à flexão, aumentaram conforme o preenchimento. O PLA, manufaturado pelo processo de FDM, demonstrou melhor performance mecânica quando produzido em eixo X com taxas de deposição de 100% para o preenchimento interno estrutural e temperatura de extrusão de 200°C. Caracteriza-se como típico frágil polimérico.

This article provides guidance into the quantitative risk assessment of skin exposures to metals. The use of wipe sampling methodologies has been shown to be standardised and effective for skin exposure assessment to metals. However, there is a lack of guidance documents and frameworks available to evaluate the level of health risk to workers from skin exposures to metals. Adverse health effects from exposures to metals have been described in the literature ( Fernandez-Nieto et al. 2006 ; Herman et al. 2006 ; Kreiss et al. 1996 ). Monitoring of workplace exposures typically focuses on the assessment of respiratory exposures. To provide a safe workplace there is a need to ensure all routes of exposure are risk assessed and controlled. The goal of this article was to develop skin (surface) exposure limits to metals, using the construction industry as a test environment, to quantitatively assess worker health risk of skin exposures to metals. This research concluded it was not feasible to establish single quantitative skin exposure limits to metals due to the many assumptions surrounding dermal exposures. A range of acceptable exposure limits are presented.

Background Although dendritic cell (DC)–based cancer vaccines represent a promising treatment strategy, its exploration in the clinic is hampered due to the need for Good Manufacturing Practice (GMP) facilities and associated trained staff for the generation of large numbers of DCs. The Quantum bioreactor system offered by Terumo BCT represents a hollow-fiber platform integrating GMP-compliant manufacturing steps in a closed system for automated cultivation of cellular products. In the respective established protocols, the hollow fibers are coated with fibronectin and trypsin is used to harvest the final cell product, which in the case of DCs allows processing of only one tenth of an apheresis product. Materials and Results We successfully developed a new protocol that circumvents the need for fibronectin coating and trypsin digestion, and makes the Quantum bioreactor system now suitable for generating large numbers of mature human monocyte-derived DCs (Mo-DCs) by processing a complete apheresis product at once. To achieve that, it needed a step-by-step optimization of DC-differentiation, e.g., the varying of media exchange rates and cytokine concentration until the total yield (% of input CD14+ monocytes), as well as the phenotype and functionality of mature Mo-DCs, became equivalent to those generated by our established standard production of Mo-DCs in cell culture bags. Conclusions By using this new protocol for the Food and Drug Administration–approved Quantum system, it is now possible for the first time to process one complete apheresis to automatically generate large numbers of human Mo-DCs, making it much more feasible to exploit the potential of individualized DC-based immunotherapy.

The ability to effect a change of direction (COD) when performing high-speed actions is essential in team sports like futsal. Nevertheless, the interaction effect of sports surfaces on this ability remains unknown. This research aimed to analyse the plantar pressures and time performance of 15 youth futsal players when performing CODs on two playing surfaces with different mechanical properties. The shock absorption and vertical deformation of one synthetic flooring surface and one wooden flooring surface were assessed. CODs were evaluated using a modified version of the Agility T-Test, while total time of the test, time of CODs, and plantar pressure in CODs were all recorded. The wooden flooring surface displayed higher values of shock absorption (35.70% ± 2.87%) and vertical deformation (2.77 ± 0.38 mm) compared with the synthetic flooring (p 0.05). Finally, no differences in plantar pressures by playing surface were found. In sum, the differences in the mechanical properties of the two futsal surfaces affected the performance of futsal players in the modified agility test. However, these differences were not great enough to generate different plantar pressures on players, probably due to playerś own adaptations. Sin financiación 4.050 JCR (2020) Q1, 21/88 Sport Sciences 1.252 SJR (2020) Q1, 382/2448 Medicine (miscellaneous) No data IDR 2020 UEM

Background aims Autologous cell therapy (AuCT) is an emerging therapeutic treatment that is undergoing transformation from laboratory- to industry-scale manufacturing with recent regulatory approvals. Various challenges facing the complex AuCT manufacturing and supply chain process hinder the scale out and broader application of this highly potent treatment. Methods We present a multiscale logistics simulation framework, AuCT-Sim, that integrates novel supply chain system modeling algorithms, methods, and tools. AuCT-Sim includes a single facility model and a system-wide network model. Unique challenges of the AuCT industry are analyzed and addressed in AuCT-Sim. Decision-supporting tools can be developed based on this framework to explore “what-if” manufacturing and supply chain scenarios of importance to various cell therapy stakeholder groups. Results Two case studies demonstrate the decision-supporting capability of AuCT-Sim where one investigates the optimal reagent base stocking level, and the other one simulates a reagent supply disruption event. These case studies serve as guidelines for designing computational experiments with AuCT-Sim to solve specific problems in AuCT manufacturing and supply chain. Discussion This simulation framework will be useful in understanding the impact of possible manufacturing and supply chain strategies, policies, regulations, and standards informing strategies to increase patient access to AuCT.

WE43, a magnesium alloy containing yttrium and neodymium as main alloying elements, has become a well-established bioresorbable implant material. Implants made of WE43 are often fabricated by powder extrusion and subsequent machining, but for more complex geometries laser powder bed fusion (LPBF) appears to be a promising alternative. However, the extremely high cooling rates and subsequent heat treatment after solidification of the melt pool involved in this process induce a drastic change in microstructure, which governs mechanical properties and degradation behaviour in a way that is still unclear. In this study we investigated the changes in the microstructure of WE43 induced by LPBF in comparison to that of cast WE43. We did this mainly by electron microscopy imaging, and chemical mapping based on energy-dispersive X-ray spectroscopy in conjunction with electron diffraction for the identification of the various phases. We identified different types of microstructure: an equiaxed grain zone in the center of the laser-induced melt pool, and a lamellar zone and a partially melted zone at its border. The lamellar zone presents dendritic lamellae lying on the Mg basal plane and separated by aligned Nd-rich nanometric intermetallic phases. They appear as globular particles made of Mg3Nd and as platelets made of Mg41Nd5 occurring on Mg prismatic planes. Yttrium is found in solid solution and in oxide particles stemming from the powder particles' shell. Due to the heat influence on the lamellar zone during subsequent laser passes, a strong texture developed in the bulk material after substantial grain growth. STATEMENT OF SIGNIFICANCE: Additively manufactured magnesium alloys have the potential of providing a major breakthrough in bone-reconstruction surgery by serving as biodegradable porous scaffold material. This study is the first to report in detail on the microstructure development of the established magnesium alloy WE43 fabricated by the additive manufacturing process of Laser Powder Bed Fusion (LPBF). It presents unique microstructural features which originate from the laser-melting process. An in situ transmission electron microscopy heating experiment further demonstrates the development of two distinct intermetallic phases in additively manufactured WE43 alloys. While one forms already during solidification, the other precipitates due to the ongoing heat treatment during LPBF processing.

Silicosis is an incurable occupational lung disease caused by inhaling particles of respirable crystalline silica. These particles trigger inflammation and fibrosis in the lungs, leading to progressive, irreversible, and potentially disabling disease. Silica exposure is also associated with increased risk for lung infection (notably, tuberculosis), lung cancer, emphysema, autoimmune diseases, and kidney disease (1). Because quartz, a type of crystalline silica, is commonly found in stone, workers who cut, polish, or grind stone materials can be exposed to silica dust. Recently, silicosis outbreaks have been reported in several countries among workers who cut and finish stone slabs for countertops, a process known as stone fabrication (2-5). Most worked with engineered stone, a manufactured, quartz-based composite material that can contain >90% crystalline silica (6). This report describes 18 cases of silicosis, including the first two fatalities reported in the United States, among workers in the stone fabrication industry in California, Colorado, Texas, and Washington. Several patients had severe progressive disease, and some had associated autoimmune diseases and latent tuberculosis infection. Cases were identified through independent investigations in each state and confirmed based on computed tomography (CT) scan of the chest or lung biopsy findings. Silica dust exposure reduction and effective regulatory enforcement, along with enhanced workplace medical and public health surveillance, are urgently needed to address the emerging public health threat of silicosis in the stone fabrication industry.

The classical method for evaluating the waveguide ability only focuses on the optical loss coefficient. However, for the micro- or submicroscale, an organic waveguide is demonstrated by the present study whose scale effect should not be neglected. We found that the optical loss coefficient increased remarkably when decreasing the sectional size of the microfibers. Furthermore, simulations based on Finite-Difference Time-Domain also demonstrated the size-dependent effect of the waveguide. Both the experimental and simulating results showed that the optical loss coefficient converges to a certain value, which means that the scale effect can be neglected as the sectional size is large enough. On the basis of the present study, we suggest that the scale-dependent effect on the sectional size of the waveguide should be investigated by evaluating the waveguide ability by the optical loss coefficient.

The microbial corrosion of oil and gas pipes is one of the problems occurring in the oil industry. Various mechanisms explaining microbial corrosion have been demonstrated. Commonly, biocorrosion is attributed to sulfate-reducing bacteria. Also, it has recently been reported that microbial species can connect their electron transport system to metal electrodes. In this research, two spore-forming bacteria isolated in different years from a gas pipeline were identified by biochemical techniques and by 16S rDNA amplification, sequencing, and comparison with the NCBI database. Isolates were also compared between them using molecular techniques as the restriction patterns, unique for 16S rDNA (ARDRA), and the profile of the amplified bit from the genomic DNA, using an unspecific primer (RAPD). The results obtained showed that both isolates corresponded to Clostridium celerecrescens with a 99% similarity according to the sequence reported on the NCBI database. Also, the ARDRA and RAPD electrophoretic profiles of both strains were identical, and no plasmids were found in the strains. Thus, it can be settled that this bacterium is persistent in the environment prevailing in gas pipelines. Also, it was demonstrated that the bacterial secretion of organic acids contributes to the pitting and general biocorrosion of API XL 52 steel. The rates of corrosion obtained, approximately after 40 days, were correlated with the presence and metabolic activity of C. celerecrescens on the metallic surfaces.

Background Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery. Study design and methods Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37°C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution. A laboratory study was conducted on six pools of ABO/D-matched units made the day after donation. On Days 7, 21, and 28 of 4 ± 2°C storage, one unit per pool was rejuvenated and measured over 96 hours for volume, hematocrit, hemolysis, ATP, 2,3-DPG, supernatant potassium, lactate, and purines added (inosine) or produced (hypoxanthine) by rejuvenation. Subsequently, an operational validation (two phases of 32 units each) was undertaken, with results from the first informing a trial component specification applied to the second. Rejuvenation effects were also tested on crossmatch reactivity and RBC antigen profiles. Results Rejuvenation raised 2,3-DPG to, and ATP above, levels of fresh cells. The final component had potassium and hemolysis values below those of standard storage Days 7 and 21, respectively, containing 1.2% exogenous inosine and 500 to 1900 μmoles/unit of hypoxanthine. The second operational validation met compliance to the trial component specification. Rejuvenation did not adversely affect crossmatch reactivity or RBC antigen profiles. Conclusion The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials.

The design and fabrication of a continuous-flow μPCR device with very short amplification time and low power consumption are presented. Commercially available, 4-layer printed circuit board (PCB) substrates are employed, with in-house designed yet industrially manufactured embedded Cu micro-resistive heaters lying at very close distance from the microfluidic network, where DNA amplification takes place. The 1.9-m-long microchannel in combination with desirably high flow velocities (for fast amplification) challenged the robustness of the sealing that was overcome with the development of a novel bonding method rendering the microdevice robust even at extreme pressure drops (12 bars). The proposed fabrication methods are PCB compatible, allowing for mass and reliable production of the μPCR device in the established PCB industry. The μPCR chip was successfully validated during the amplification of two different DNA fragments (and with different target DNA copies) corresponding to the exon 20 of the BRCA1 gene, and to the plasmid pBR322, a commonly used cloning vector in E. coli. Successful DNA amplification was demonstrated at total reaction times down to 2 min, with a power consumption of 2.7 W, rendering the presented μPCR one of the fastest and lowest power-consuming devices, suitable for implementation in low-resource settings. Detailed numerical calculations of the DNA residence time distributions, within an acceptable temperature range for denaturation, annealing, and extension, performed for the first time in the literature, provide useful information regarding the actual on-chip PCR protocol and justify the maximum volumetric flow rate for successful DNA amplification. The calculations indicate that the shortest amplification time is achieved when the device is operated at its enzyme kinetic limit (i.e., extension rate). Graphical abstract.

Background/Aims: Recently, to lower the production costs and risk of infection, new disposable biopsy forceps made using simple manufacturing techniques have been introduced. However, the effects of the manufacturing techniques are unclear. The aim of this study was to evaluate which types of biopsy forceps could obtain good-quality specimens according to the manufacturing techniques. Methods: By using an in vitro nitrile glove popping model, we compared the pop ping ability among eight different disposable biopsy forceps (one pair of biopsy forceps with cups made by a cutting method [cutting forceps], four pairs of biopsy forceps with cups made by a pressing method [pressing forceps], and three pairs of biopsy forceps with cups made using a injection molding method [molding forceps]). Using an in vivo swine model, we compared the penetration depth and quality of specimen among the biopsy forceps. Results: In the in vitro model, the molding forceps provided a significantly high er popping rate than the other forceps (cutting forceps, 25.0%; pressing forceps, 17.5%; and molding forceps, 41.7%; p = 0.006). In the in vivo model, the cutting and pressing forceps did not provide larger specimens, deeper biopsy specimen, and higher specimen adequacy than those obtained using the molding forceps (p = 0.2631, p = 0.5875, and p = 0.2147, respectively). However, the molding forceps showed significantly more common crush artifact than the others (cutting for ceps, 0%; pressing forceps, 5.0%; and molding forceps, 43.3%; p = 0.0007). Conclusions: The molding forceps provided lower performance than the cutting and pressing forceps in terms of crush artifact.

Additive manufacturing (AM) is a disruptive technology as it pushes the frontier of manufacturing towards a new design perspective, such as the ability to shape geometries that cannot be formed with any other traditional technique. AM has today shown successful applications in several fields such as the biomedical sector in which it provides a relatively fast and effective way to solve even complex medical cases. From this point of view, the purpose of this paper is to illustrate AM technologies currently used in the medical field and their benefits along with contemporary. The review highlights differences in processes, materials, and design of additive manufacturing techniques used in biomedical applications. Successful case studies are presented to emphasise the potentiality of AM processes. The presented review supports improvements in materials and design for future researches in biomedical surgeries using instruments and implants made by AM.

Conventional signal-based microanalytical techniques for estimating bacterial concentrations are often susceptible to false signals. A visual quantification, therefore, may compliment such techniques by providing additional information and support better management decisions in the event of outbreaks. Herein, we explore a method that combines electron microscopy (EM) and image-analysis techniques and allows both visualization and quantification of pathogenic bacteria adherent even to complex nonuniform substrates. Both the estimation and imaging parameters were optimized to reduce the estimation error ( E, %) to close to ±5%. The method was validated against conventional microbiological techniques such as the use of optical density, flow cytometry, and quantitative real-time PCR (qPCR). It could easily be tailored to estimate different species of pathogens, such as Escherichia coli O157, Listeria innocua, Staphylococcus aureus, Enterococcus faecalis, and Bacillus anthracis, on samples similar to those in real-time contamination scenarios. The present method is sensitive enough to detect ∼100 bacterial CFU/mL but has the potential to estimate even lower concentrations with increased imaging and computation times. Overall, this imaging-based method may greatly complement any signal-based pathogen-detection technique, especially in negating false signals, and therefore may significantly contribute to the field of analytical microbiology and biochemistry.

Residual chemicals on personal care and healthcare products, such as sanitary articles, sterile gauze bandages, nappies, plasters, were studied by direct analysis in real time mass spectrometry (DART-MS). We have identified around 40 compounds in seventeen different commercially available items. The tentative identification was further supported for about half of the chemicals by tandem mass spectrometric experiments (DART MS/MS). The most notable hazardous substances were tributyl phosphate, tris(2,4-di-tert-butylphenyl) phosphite, phthalic acid esters, erucamide, and nonylphenol ethoxylates (NPEs). In addition, we developed an efficient DART-MS analysis to determine the concentration of NPE in a swab sample. The quantitative result obtained by DART-MS was confirmed by liquid chromatography with mass spectrometric detection (LC-MS).

Additive manufacturing (AM) is an effective tool for accelerating knowledge gain in development processes, as it enables the production of complex prototypes at low cost and with short lead times. In the development of mechanical circulatory support, the use of cheap polymer-based AM techniques for prototype manufacturing allows more design variations to be tested, promoting a better understanding of the respective system and its optimization parameters. Here, we compare four commonly used AM processes for polymers with respect to manufacturing accuracy, surface roughness, and shape fidelity in an aqueous environment. Impeller replicas of the CentriMag blood pump were manufactured with each process and integrated into original pump housings. The assemblies were tested for hydraulic properties and hemolysis in reference to the commercially available pump. Computational fluid dynamic simulations were carried out to support the transfer of the results to other applications. In hydraulic testing, the deviation in pressure head and motor current of all additively manufactured replicas from the reference pump remained below 2% over the entire operating range of the pump. In contrast, significant deviations of up to 620% were observed in hemolysis testing. Only the replicas produced by stereolithography showed a nonsignificant deviation from the reference pump, which we attribute to the low surface roughness of parts manufactured thereby. The results suggest that there is a flow-dependent threshold of roughness above which a surface strongly contributes to cell lysis by promoting a hydraulically rough boundary flow.

Masks constructed of a variety of materials are in widespread use due to the COVID-19 pandemic, and people are exposed to chemicals inherent in the masks through inhalation. This work aims to survey commonly available mask materials to provide an overview of potential exposure. A total of 19 mask materials were analyzed using a nontargeted analysis two-dimensional gas chromatography (GCxGC)-mass spectrometric (MS) workflow. Traditionally, there has been a lack of GCxGC-MS automated high-throughput screening methods, resulting in trade-offs with throughput and thoroughness. This work addresses the gap by introducing new machine learning software tools for high-throughput screening (Floodlight) and subsequent pattern analysis (Searchlight). A recursive workflow for chemical prioritization suitable for both manual curation and machine learning is introduced as a means of controlling the level of effort and equalizing sample loading while retaining key chemical signatures. Manual curation and machine learning were comparable with the mask materials clustering into three groups. The majority of the chemical signatures could be characterized by chemical class in seven categories: organophosphorus, long chain amides, polyethylene terephthalate oligomers, n-alkanes, olefins, branched alkanes and long-chain organic acids, alcohols, and aldehydes. The olefin, branched alkane, and organophosphorus components were primary contributors to clustering, with the other chemical classes having a significant degree of heterogeneity within the three clusters. Machine learning provided a means of rapidly extracting the key signatures of interest in agreement with the more traditional time-consuming and tedious manual curation process. Some identified signatures associated with plastics and flame retardants are potential toxins, warranting future study to understand the mask exposure route and potential health effects.

In this study, a novel air-ring flow regulating valve was proposed to reduce the flow resistance caused by valve structural pressure drop in fluid transportation pipeline system. The regulating characteristics at different valve openings were analyzed by numerical method and the results were compared with the center butterfly valve which is most widely applied in fluid transportation pipeline system. Besides, an experimental system was designed to validate the numerical model in the present study. The results indicated that the simulation results agree well with experimental data. The resistance coefficient of the air-ring flow regulating valve is smaller than that of the center butterfly valve when the valve opening is greater than 67%, and the resistance coefficient is reduced by up to 100% as the valve is fully opened. Both valves maintain approximately equal percentage flow characteristics, the deviation in relative flow coefficient is small. In addition, the wall shear stress of the air-ring flow regulating valve is much smaller than that of the center butterfly valve at the same valve opening, and the maximum velocity in the pipeline system is always smaller than that of the center butterfly valve, which significantly reduces valve surface abrasive erosion and thus prolongs its service life.

BACKGROUND Allergic contact dermatitis caused by shoes is common and new relevant allergens have been identified. OBJECTIVES To investigate the pattern of type IV sensitization in patients with suspected allergic contact dermatitis of the feet related to shoes as a presumed culprit trigger. METHODS Retrospective analysis of data of the Information Network of Departments of Dermatology (IVDK), 2009-2018. RESULTS Six hundred twenty-five patients with presumed shoe dermatitis were identified in a cohort of 119���417 patients. Compared to patients with suspected contact sensitization from other allergen sources (n��=��118���792), study group patients were more frequently sensitized to potassium dichromate (10.8% vs 3.5%), colophony (7.2% vs 3.7%), mercaptobenzothiazole (MBT; 4.0% vs 0.6%), mercapto mix (4.6% vs 0.6%), and p-tert-butylphenol formaldehyde resin (1.6% vs 0.5%). Sensitizations to urea formaldehyde resin, melamine formaldehyde resin, glutaraldehyde, tricresyl phosphate, and phenyl glycidylether were rare. Moreover, reactions to compounds in the leather or textile dyes test series were scarce. CONCLUSION A distinct sensitization pattern was observed in patients with suspected allergy to shoe materials. Although substances with low sensitization rates should be removed from the leather and shoe patch test series, novel potential allergens should be added.

Intense predation pressure from echolocating bats has led to the evolution of a host of anti-bat defences in nocturnal moths. The wings of moths are covered in scales that exhibit intricate shapes and sculpted nano structures. Here, we reveal that this scale layer forms a metamaterial ultrasound absorber that is 111 times thinner than the longest absorbed wavelength. Both experimental and numerical analyses of individual scale vibrodynamics reveal that the first three resonances of moth scales lie within the typical echolocation frequency range of bats, whilst scale shape diversity on the wing results in a broad resonance distribution. Individual scales form the resonant unit-cells on the wing and collectively they generate hard to attain broadband deep-subwavelength absorption. Numerical modelling confirms that the acoustic properties of moth wings originate from the interaction of differently tuned single scale resonators, creating emergent acoustic performance beyond that of its elements, confirming broadband metamaterial absorber functionality. This sound absorber provides moth wings with acoustic camouflage against echolocating bats, it combines broadband absorption of all frequencies used by bats with light and ultrathin structures that meet aerodynamic constraints on wing weight and thickness.