A multiscale simulation framework for the manufacturing facility and supply chain of autologous cell therapies.

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.

Computational modeling of fatigue crack propagation in butt welded joints subjected to axial load.

This article addresses the study of crack behavior elicited on axial fatigue in specimens joined by butt weld made of steel ASTM A36 by using fracture mechanics and simulation software of finite elements (Ansys APDL, Franc3D). The computational model was initially to define the geometry model by using CAD software. Specimens with Weld Reinforcement of 2 mm and 3mm were simulated. Subsequently, the type of element for the mesh, the information inclusion concerning material mechanical properties and load conditions were selected. By using Franc3D software, the crack propagation phenomenon is analyzed, and its growth parameters have been established. In this way, it is possible to calculate the magnitude of stress intensity factor (SIF) along the crack front. It is concluded that the stress located in the weld toe is maximized proportionately to the size of the weld reinforcement due to the concentration effect of geometric stress. In addition, it is observed that the propagation rate obtained from Paris law has a similar behavior for the studied weld reinforcements; the latter as there were short cracks.

Evaluating the consumption of chemical products and articles as proxies for diffuse emissions to the environment.

In this study we have evaluated the use of consumption of manufactured products (chemical products and articles) in the EU as proxies for diffuse emissions of chemicals to the environment. The content of chemical products is relatively well known. However, the content of articles (products defined by their shape rather than their composition) is less known and currently has to be estimated from chemicals that are known to occur in a small set of materials, such as plastics, that are part of the articles. Using trade and production data from Eurostat in combination with product composition data from a database on chemical content in materials (the Commodity Guide), we were able to calculate trends in the apparent consumption and in-use stocks for 768 chemicals in the EU for the period 2003-2016. The results showed that changes in the apparent consumption of these chemicals over time are smaller than in the consumption of corresponding products in which the chemicals are present. In general, our results suggest that little change in chemical consumption has occurred over the timespan studied, partly due to the financial crisis in 2008 which led to a sudden drop in the consumption, and partly due to the fact that each of the chemicals studied is present in a wide variety of products. Estimated in-use stocks of chemicals show an increasing trend over time, indicating that the mass of chemicals in articles in the EU, that could potentially be released to the environment, is increasing. The quantitative results from this study are associated with large uncertainties due to limitations of the available data. These limitations are highlighted in this study and further underline the current lack of transparency on chemicals in articles. Recommendations on how to address these limitations are also discussed.

Prevalence of Artificial Food Colors in Grocery Store Products Marketed to Children.

Artificial food colors (AFCs) in foods and beverages may be harmful to children. This study assesses the percentage of grocery store products marketed to children that contain AFCs, by category and company. The research team collected product and food-color information about 810 products in one grocery store in North Carolina in 2014. Overall, 350 products (43.2%) contained AFCs. The most common AFCs were Red 40 (29.8% of products), Blue 1 (24.2%), Yellow 5 (20.5%), and Yellow 6 (19.5%). Produce was the only category that did not have any AFCs. The highest percentage of products with AFCs was found in candies (96.3%), fruit-flavored snacks (94%), and drink mixes/powders (89.7%). Forty-one of the 66 companies marketed products containing AFCs. Given concerns about health effects of AFCs and high proportions of high-AFC categories, clinicians, parents, food companies, and the government can take steps to support children's healthy eating and development by reducing AFCs in children's diets.

Paper recycling framework, the "Wheel of Fiber".

At present, there is no reliable method in use that unequivocally describes paper industry material flows and makes it possible to compare geographical regions with each other. A functioning paper industry Material Flow Account (MFA) that uses uniform terminology and standard definitions for terms and structures is necessary. Many of the presently used general level MFAs, which are called frameworks in this article, stress the importance of input and output flows but do not provide a uniform picture of material recycling. Paper industry is an example of a field in which recycling plays a key role. Additionally, terms related to paper industry recycling, such as collection rate, recycling rate, and utilization rate, are not defined uniformly across regions and time. Thus, reliably comparing material recycling activity between geographical regions or calculating any regional summaries is difficult or even impossible. The objective of this study is to give a partial solution to the problem of not having a reliable method in use that unequivocally describes paper industry material flows. This is done by introducing a new material flow framework for paper industry in which the flow and stage structure supports the use of uniform definitions for terms related to paper recycling. This new framework is termed the Detailed Wheel of Fiber.

Multidisciplinary Testing of Floor Pads on Stability, Energy Absorption, and Ease of Hospital Use for Enhanced Patient Safety.

OBJECTIVES: A major improvement in hospital safety could be realized if serious injury did not accompany falls. We studied several commercially available floor pads made of different materials to determine which (if any) would be practical in a hospital room and reduce injury without posing a threat to the balance of patients. METHODS: A multidisciplinary approach was undertaken to (1) measure upper and lower body motion in 17 young (<50 years) and 17 older (>55 years) adults during an instrumented sit to stand test from a hospital bed onto the different floor pads, (2) predict the energy dissipation available in floor pads by quantifying the relative mechanical properties, and (3) obtain professional feedback from hospital nurses via a questionnaire (8 questions) following a period of working on the different floor pads. Five floor pads, composed of foam, gel, and/or rubber were tested. All pads were compared with a typical hospital floor (concrete covered with linoleum tiles, considered the control). RESULTS: All of the pads subject to mechanical testing showed at least 3 times more energy absorption compared with the control. Balance testing showed that three of the pads resulted in minimal or no significant increases in body motion during sit-to-stand. Nursing feedback revealed that only 2 of these 3 pads may be feasible for hospital room use: one made primarily of firm rubber and one made of foam. CONCLUSIONS: Floor pads do exist that show promise for hospital use that absorbing energy without major impacts on balance during sit-to-stand. Although only commercially available pads were investigated, results may inform the design and multidisciplinary testing of other floor surfaces.

The effect of field condition and shoe type on lower extremity injuries in American Football.

BACKGROUND/AIM: Considerable improvement has been made in football field surfaces and types of shoe, yet relatively few epidemiological studies have investigated their roles in the risk of football injuries. This study examined the effects of field surface, surface condition and shoe type on the likelihood of lower extremity football injuries. METHODS: Deidentified data from 188 players from one division I university football team during the 2007-2010 seasons were analysed. Lower extremity injury rate and rate ratio, along with 95% confidence limits, were calculated by football activity, playing surface condition and shoe type. RESULTS: A total of 130 lower extremity injuries were sustained, with an overall lower extremity injury rate of 33.5/10 000 athlete-sessions. The lower extremity injury rate was 2.61 times higher when the surface condition was abnormal compared with when the surface condition was normal. During games, the risk for lower extremity injury was 3.34 times higher (95% CI 1.70 to 6.56) on artificial turf compared with natural grass. However, this trend was not statistically significant in practice sessions. Furthermore, neither the number of shoe cleats nor the height of the shoe top was statistically associated with risk of lower extremity injuries. CONCLUSIONS: Football players who played on artificial turf or when the surface condition was abnormal were susceptible to lower extremity injuries. Evidence from this study suggests that further research into playing surfaces and shoe types may provide fruitful opportunities to reduce injuries to collegiate football players.

Long-term health experience of jet engine manufacturing workers: VIII. glioblastoma incidence in relation to workplace experiences with parts and processes.

OBJECTIVE: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed. METHODS: Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases. RESULTS: In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk. CONCLUSIONS: If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.

Ecotoxicity of manufactured ZnO nanoparticles--a review.

This report presents an exhaustive literature review on the toxicity of manufactured ZnO nanoparticles (NPs) to ecological receptors across different taxa: bacteria, algae and plants, aquatic and terrestrial invertebrates and vertebrates. Ecotoxicity studies on ZnO NPs are most abundant in bacteria, and are relatively lacking in other species. These studies suggest relative high acute toxicity of ZnO NPs (in the low mg/l levels) to environmental species, although this toxicity is highly dependent on test species, physico-chemical properties of the material, and test methods. Particle dissolution to ionic zinc and particle-induced generation of reactive oxygen species (ROS) represent the primary modes of action for ZnO NP toxicity across all species tested, and photo-induced toxicity associated with its photocatalytic property may be another important mechanism of toxicity under environmentally relevant UV radiation. Finally, current knowledge gaps within this area are briefly discussed and recommendations for future research are made.

Diversity of containers and buildings infested with Aedes aegypti in Puerto Iguazú, Argentina.

Aedes aegypti is the main domestic vector of the dengue virus. Control measures to prevent dengue transmission focus on the treatment and elimination of this vector's oviposition sites. There is limited biological information on Ae. aegypti in Argentina. The aim of this study was to characterize Ae. aegypti oviposition sites in the city of Puerto Iguazú, Argentina. We surveyed an area covering nine neighborhoods in 2005. We identified 191 premises as positive for Ae. aegypti, giving a general house index of 9.6%. Premises classified as residential and vacant lots presented the highest number of infested premises, with 9% and 22% respectively. The total number of surveyed containers was 29,600. The overall container index (CI) was 1.1. The most frequently infested containers were water tanks (CI = 37). These preliminary results suggest that vacant lots and water tanks provide suitable breeding areas and environmental conditions, improving the chances of Ae. aegypti survival in Puerto Iguazú.

Quantifying capital goods for collection and transport of waste.

The capital goods for collection and transport of waste were quantified for different types of containers (plastic containers, cubes and steel containers) and an 18-tonnes compacting collection truck. The data were collected from producers and vendors of the bins and the truck. The service lifetime and the capacity of the goods were also assessed. Environmental impact assessment of the production of the capital goods revealed that, per tonne of waste handled, the truck had the largest contribution followed by the steel container. Large high density polyethylene (HDPE) containers had the lowest impact per tonne of waste handled. The impact of producing the capital goods for waste collection and transport cannot be neglected as the capital goods dominate (>85%) the categories human-toxicity (non-cancer and cancer), ecotoxicity, resource depletion and aquatic eutrophication, but also play a role (>13%) within the other impact categories when compared with the impacts from combustion of fuels for the collection and transport of the waste, when a transport distance of 25 km was assumed.

Parental occupational exposure to exhausts, solvents, glues and paints, and risk of childhood leukemia.

PURPOSE: It is unknown whether parental occupational exposure to chemicals before during and after pregnancy increases the risk of acute lymphoblastic leukemia (ALL) in the offspring. Few studies on this topic have assessed maternal exposures. METHODS: In an Australian case-control study of ALL in children aged <15 years, parents were asked about tasks they undertook in each job using a set of job-specific modules (JSMs). An expert reviewed the likelihood of exposure to exhausts, solvents, glues, and paints. Exposure was examined in each job 2 years, 1 year and anytime before birth of the child, and up to 1 year after birth of child. RESULTS: Solvent exposure was similar for case and control mothers in all time periods. More case mothers had moderate/high exposure to exhausts than control mothers anytime before the birth of the child (p = 0.010). Exposure to moderate or substantial levels of exhausts by mothers (OR = 1.97 95% CI 0.99-3.90) or fathers (OR = 1.37 95% CI 1.01-1.86) before the birth increased the risk of ALL in their offspring. Exposure to paints, pigments, glues, and resins was similar in case and control parents. CONCLUSION: We found little evidence that parental occupational exposure to solvents, glues, and paints was associated with childhood ALL. There was some evidence ALL was associated with exhaust exposure.

Remanufacturing and energy savings.

Remanufactured products that can substitute for new products are generally claimed to save energy. These claims are made from studies that look mainly at the differences in materials production and manufacturing. However, when the use phase is included, the situation can change radically. In this Article, 25 case studies for eight different product categories were studied, including: (1) furniture, (2) clothing, (3) computers, (4) electric motors, (5) tires, (6) appliances, (7) engines, and (8) toner cartridges. For most of these products, the use phase energy dominates that for materials production and manufacturing combined. As a result, small changes in use phase efficiency can overwhelm the claimed savings from materials production and manufacturing. These use phase energy changes are primarily due to efficiency improvements in new products, and efficiency degradation in remanufactured products. For those products with no, or an unchanging, use phase energy requirement, remanufacturing can save energy. For the 25 cases, we found that 8 cases clearly saved energy, 6 did not, and 11 were too close to call. In some cases, we could examine how the energy savings potential of remanufacturing has changed over time. Specifically, during times of significant improvements in energy efficiency, remanufacturing would often not save energy. A general design trend seems to be to add power to a previously unpowered product, and then to improve on the energy efficiency of the product over time. These trends tend to undermine the energy savings potential of remanufacturing.

Potential exposure of German consumers to engineered nanoparticles in cosmetics and personal care products.

The rapid increase in the number of consumer products containing engineered nanoparticles (ENP) raises concerns about an appropriate risk assessment of these products. Along with toxicological data, exposure estimates are essential for assessing risk. Currently, cosmetics and personal care products (C&PCP) represent the largest ENP-containing consumer product class on the market. We analyzed factors influencing the likelihood that ENP-containing products are available to consumers. We modelled potential external exposure of German consumers, assuming a maximum possible case where only ENP-containing products are used. The distribution of exposure levels within the population due to different behavior patterns was included by using data from an extensive database on consumer behavior. Exposure levels were found to vary significantly between products and between consumers showing different behavior patterns. The assessment scheme developed here represents a basis for refined exposure modelling as soon as more specific information about ENPs in C&PCP becomes available.

Appreciating the role of thermodynamics in LCA improvement analysis via an application to titanium dioxide nanoparticles.

Although many regard it as the most important step of life cycle assessment, improvement analysis is given relatively little attention in the literature. Most available improvement approaches are highly subjective, and traditional LCA methods often do not account for resources other than fossil fuels. In this work exergy is evaluated as a thermodynamically rigorous way of identifying process improvement opportunities. As a case study, a novel process for producing titanium dioxide nanoparticles is considered. A traditional impact assessment, a first law energy analysis, and an exergy analysis are done at both the process and life cycle scales. The results indicate that exergy analysis provides insights not available via other methods, especially for identifying unit operations with the greatest potential for improvement. Exergetic resource accounting at the life cycle scale shows that other materials are at least as significant as fossil fuels for the production of TiO2 nanoparticles in this process.

Life cycle assessment of a road safety product made with virgin and recycled HDPE.

The present study aims at evaluating the potential environmental impact of using recycled high-density polyethylene (HDPE) in the production of an anti-glare lamella (AGL), a road safety device currently manufactured from virgin (not recycled) polymer. The impact was evaluated using the life cycle assessment (LCA) technique and comparing two alternative systems: current AGL, manufactured from virgin HDPE, and optional AGL, made with recycled HDPE obtained from post-consumer packages. The AGL manufacturing phase was found to be responsible for most of the impacts in both systems, with the production of the raw material being the largest contributor for that phase. The present study makes a contribution to the problem of developing value-added products made from post-consumer polymeric recyclates.