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Background: Amyloid-β (Aβ), the key constituent of Alzheimer’s disease (AD) plaques, has antimicrobial properties. Objective: To investigate the association between plasma Aβ and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae. Methods: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aβ40 and Aβ42 concentrations with Luminex xMAP technology and INNOBIA plasma Aβ-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases. Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aβ42 or Aβ40 in cases or controls. Conclusion: Levels of plasma Aβ were not associated with antibodies against different AD-related pathogens.

Introduction: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD. Methods: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year. Results: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018). Discussion: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.

Introduction Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster-virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes-infected individuals. Methods The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year. Results Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74). Discussion Antiviral treatment was associated with a reduced long-term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.

Background: Amyloid-beta (A beta), the key constituent of Alzheimer's disease (AD) plaques, has antimicrobial properties. Objective: To investigate the association between plasma A beta and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae. Methods: Plasma from 339 AD cases, obtained on average 9.4 years (+/- 4.00) before diagnosis, and their matched controls were analyzed for A beta(40) and A beta(42) oncentrations with Luminex xMAP technology and INNOBIA plasma A beta-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases. Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of A beta 42 or A beta 40 in cases or controls. Conclusion: Levels of plasma A beta were not associated with antibodies against different AD-related pathogens.

Progressive stamping tools are widely used in mass-production of sheet metal components and their performance is critical as the design of the tool impact the cost of the manufactured component significantly. Knowledge reuse is an important part of successful design in general, and in progressive stamping tool design in particular. In the study described in this paper, 8 tool designers from 5 different Swedish companies were interviewed about (1) at what points in the tool design process they search for previously designed tools for information and knowledge reuse, (2) under what conditions and for what reasons does this reuse take place, and (3) what types of information and knowledge are sought for at each point. The results show that reuse of information and knowledge from previously designed tools happens in many parts of the tool design process. The reasons and conditions for reuse vary depending on where in the process the designer is. High component complexity is one example of a common factor triggering reuse. Also, information about the performance of the tool is important to tool designers, as they only want to reuse information and knowledge from tools with good performance and low maintenance.

New business opportunities are created when the advantage of changeable manufacturing systems expand beyond increased freedom in production location to increased freedom in product design. However, there are new challenges to overcome, including improved ability to design and adapt products when requirements from stakeholders quickly change and/or new technology rapidly evolves. Simultaneously, the producibility of each design must be ensured while keeping the lead-time of the whole process to the minimum. Changeable product platforms (both flexible and adaptable platforms) are gaining attention in both research and industry. However, the level of alignment and integration of product development and production is critical for the efficiency of the product realization process. In this study, we map the state of practice in five companies with an initial literature review. The companies had no formal platform strategy and faced challenges with variant management and development time, had manual processes for production preparation and reuse of technical solutions and knowledge happened through components and documents. The production preparation and reuse were dependent on the engineer’s competence. Future work will concentrate on identifying how manufacturing inputs can be added as a design asset in a changeable product platform to enhance producibility and production preparation., Virtual Conference, Online.

From the Introduction: Some companies represent their product family design as a space of design alternatives. The design space is a mathematical space that is governed by applying a set of design rules to design parameters. A key principle in establishing a design space instead of developing a single solution is to put minimum requirements for design optimization in the early stages of development. Developing a new design variant requires understanding the base design and adapting the design according to the new requirements. Use of design rationale can provide such understanding. With increasing the number of variants, access to design rationale becomes more important. Understanding why a design variant was accepted and if there have been any other alternatives in the beginning but were rejected (due to functionality or manufacturing limitations) can help the designers to avoid developing new design variants that have previously been proven wrong. Or it can support the designers to propose design variants that can be accepted under specific conditions for unique customers. The repetitive and time consuming design activities can be assigned to design automation systems in order to increase efficiency and shorten the lead time. The use of design automation system is more vital when the number of design variants drastically increase. Use of Domain Specific Language (DSL) can amplify the applicability of the design automation system by targeting specific domains. A DSL is a computer language that is developed focusing on a particular application domain [3] (some DSLs are widespread such as SQL which is used for database querying, but many are note widespread). In this paper, a method is presented for capturing and sharing design rationale for each design variant in an integrated design environment. An argumentation-based approach is used for capturing design rationale. An industrial partner which has a long tradition in automating its design process has been involved, CAD'21 was planned to be held in Barelona, July 5-7, 2021. Due to COVID-19, it was moved online.

Increasing evidence implicates HSV type 1 (HSV1) in the pathogenesis of late-onset Alzheimer disease (AD). HSV1 has evolved highly sophisticated strategies to evade host immunosurveillance. One strategy involves encoding a decoy Fc gamma receptor (Fc gamma R), which blocks Fc-mediated effector functions, such as Ab-dependent cellular cytotoxicity. Ig gamma marker (GM) allotypes, encoded by highly polymorphic IGHG genes on chromosome 14q32, modulate this immunoevasion strategy, and thus may act as effect modifiers of the HSV1-AD association. In this nested case-control human study, 365 closely matched case-control pairs-whose blood was drawn on average 9.6 y before AD diagnosis-were typed for GM alleles by a TagMan genotyping assay. APOE genotype and a genetic risk score based on nine additional previously known AD risk genes (ABCA7, BIN1, CD33, CLU, CR1, EPHA1, MS4A4E, NECTIN2, and PICALM) were extracted from a genome-wide association study analysis. Antiviral Abs were measured by ELISA. Conditional logistic regression models were applied. The distribution of GM 3/17 genotypes differed significantly between AD cases and controls, with higher frequency of GM 17/17 homozygotes in AD cases as compared with controls (19.8 versus 10.7%, p = 0.001). The GM 17/17 genotype was associated with a 4-fold increased risk of AD (odds ratio 4.142,p < 0.001). In conclusion, the results of this study demonstrate that Ig GM 17/17 genotype contributes to the risk of later AD development, independent of apolipoprotein epsilon 4 genotype and other AD risk genes, and explain, at least in part, why every HSV1-infected person is not equally likely to develop HSV1-associated AD.

One interesting method to take advantage of the particular capabilities of Additive Manufacturing is to utilize a combination of lattice-structures and topology optimization. This paper presents the results and experiences from attempting to incorporate these in an existing multidisciplinary design automation system within the aerospace industry. A combined state of art and practice is outlined with discussions regarding challenges in current commercial CAD tools, multidisciplinary design automation, and with respect to aerospace requirements.

BACKGROUND: Chlamydia trachomatis salpingitis causes inflammatory damage to the fallopian tube and could potentially cause initiation and progression of high-grade serous ovarian cancer (HGSC). Furthermore, C. trachomatis infection may stimulate mucin 1 (MUC1) protein production, possibly affecting anti-MUC1 antibody levels. The aim of this study was to examine if serology indicating past infection with C. trachomatis as well as anti-MUC1 production was associated with subsequent risk of HGSC. MATERIALS AND METHODS: In a prospective nested case-control study within the Northern Sweden Health and Disease Study and the Northern Sweden Maternity Cohort, the prevalence of chlamydial and anti-MUC1 antibodies was analyzed in blood samples drawn more than one year before diagnosis from 92 women with HGSC and 359 matched controls. Matching factors were age, date at blood draw, and sampling cohort. Plasma C. trachomatis IgG was analyzed using commercial micro-immunofluorescence test; chlamydial Heat Shock Protein 60 IgG (cHSP60) and anti-MUC1 IgG were analyzed with ELISA technique. RESULTS: The prevalence of C. trachomatis IgG and cHSP60 IgG antibodies, as well as the level of anti-MUC1 IgG was similar in women with HGSC and controls (16.3% vs. 17.0%, P = 0.87; 27.2% vs. 28.5%, P = 0.80; median 0.24 vs. 0.25, P = 0.70). Anti-MUC1 IgG and cHSP60 IgG levels were correlated (r = 0.169; P < 0.001). CONCLUSIONS: The findings of this prospective nested case-control study did not support an association between C. trachomatis infection, as measured by chlamydial serology, or anti-MUC1 IgG antibodies, and subsequent risk of HGSC.

Demanding markets and complex products are only some of the reasons that make changes and variations inevitable through different stages of product realization. From early phases of product development to downstream production phase, these changes or variations cause failure either directly or by propagating to other phases, triggering more fluctuations like the well-known butterfly effect. In this paper, first, the definition of changes in product realization will be reviewed and then different papers and their classification on change related system properties (illites) will be discussed and compared. It was argued that considering a system-level view, one could trace these propagations in the systems as a result of not being robust, flexible, or adaptable, etc. Some of the ambiguity in this semantic field demonstrated and most repeated definitions are identified as the unanimous and agreed-upon definitions in the literature. In the end, a historical comparison of the three identified properties presented. The results of this study help us to understand the multidisciplinary nature of these propagations and identify their stemming turbulent environment. This will be used as a foundation for forthcoming research either to prevent these propagations or utilize their attributes in the product realization.

Design automation can be used to support efficient information handling and knowledge processing in computer-based product modelling, as well as make possible new design exploration and optimisation capabilities. To be able to utilise and manage design automation systems over time, it is important to understand how the disciplinary methods and models are dependent on each other through the product model constituents and then how these relations should be built to support maintenance, leveraging and future reuse. Awareness of the concrete representation of relations could support the system's traceability and transparency, and depending on the chosen technique, comprehension and extendability can be affected. This paper presents a conceptual framework for how a set of product model constituents are, can and to some extent, should be extended to define relations in multidisciplinary design automation systems., Included in thesis in manuscript form.

The selective laser melting (SLM) process has created new possibilities for the manufacture of new lightweight jet engine components with lattice structures replacing solid sections. Hopes are to reduce the density of the component and thereby saving weight. To introduce the new manufacturing process, the components need to be redesigned and verified to comply with an array of requirements concerning, for example, strength, aerodynamics, and manufacturing. To find out how a capability of designing and evaluating components for the SLM process can be built into an organization, an interview investigation has been conducted at an aerospace company finding the state of practice in technology and product development. The impact of introducing SLM is thereafter estimated. The result is that introducing a novel manufacturing process will primarily influence the methods used to predict product lifecycle performance. An important finding is that it is currently difficult to include a topology optimization step in the multiobjective design evaluation environment used at the company due to which the complexity would increase significantly., Selected paper from the 25th ISTE International Conference on Transdisciplinary Engineering, 3–6 July 2018, Modena, Italy.

There is a demand on the current markets of industrialized house building for higher product design flexibility and customization. One of the success factors in addressing this challenge efficiently is the formalization and use of product platforms through information technology applications. However, there is a lack of knowledge on how product platforms and their use should be modeled to support the development of information technology applications. The aim of this paper is therefore, to increase the knowledge on information modeling of product platforms and their use in the industrialized house building design process. The available information modeling methods were identified and analyzed using literature review while considering the contextual criteria of industrialized house building. An information modelling method for product platforms and their use in the industrialized house building design process is proposed. The information modeling rationale is synthesized using the design platform modeling and the information delivery manual modeling. The former is a PLM-oriented while the latter is a BIM-oriented information modeling method. The proposed information modeling method is composed of three parts: product platform information model, process maps and exchange requirement specification. Future work should aim for the validation of the proposed information modeling method by application on empirical data in a case study., Online conference due to COVID-19.

Industrialised house builders in Sweden have been challenged to meet the demand for housing solutions as the population has increased at a faster rate. As a result, the housing industry is currently faced with objectives to improve productivity and internal efficiency while also controlling the production cost of houses without compromising external efficiency. To remain competitive, many companies developed own building system (BS) based on fixed or partially fixed production systems with different prefabrication techniques. The challenges remain in the design phase and proper methods and tools are required to manage it. In many industries, the product platform approach has been used as a means to achieve both internal and external efficiency. However, little attention has been paid in relating the platform approach to building system support in the design phase of Industrialised house building (IHB). Thus, the main purpose of this paper is to explore the current state of the industrialised house building system and outline design support solutions for the building system from a product platform approach. Qualitative research was conducted by linking a single case company working with post and beam building system in combination with a literature review. Empirical data were gathered from five semi-structured interviews and two workshop sections. A cause-effect analysis has been conducted to realize the potential causes of challenges in the design process. The result illustrates a methodology with principle solutions that can be used as design support for the case company as a path forward and improve further from a product platform perspective., The symposium was held online on 7 & 8 October 2020 because of restrictions due to the Corona virus pandemic. Included in thesis in manuscript form.

House building projects are distinctive, and the degree of customisation creates bottlenecks in the design process and challenges for production, which results in longer lead time and higher costs. Aligned with a product platform approach, previous studies have introduced cost-effective approaches such as standardisation, modularization, configurators, etc. Still, components that cannot be completely modularized and configured due to high complexity level, may require a lot of engineering efforts during development. A platform approach that can be used to support engineer-to-order products that change over time still needs to be explored. The application of parametric modelling to automate the design process in the construction industry has the potential to further increase both the design and production efficiency. Thus, the objective of this research is to apply parametric modelling in the design of steel connectors used in a glulam based post and beam building system as part of a flexible product platform for increased design and production efficiency. A single case study has been carried out with a Swedish multi-storey house building company. Empirical data were gathered from a workshop with the design team followed by interviews, and document analysis. A computer-supported method for the steel bracket connectors has been developed, that connects post and beam components with pre-defined rules and constraints as part of the platform development. The result contributes to expanding knowledge about the development of a flexible product platform for improved design process and downstream production of customised components with parametric modelling support in the industrial post and beam buildng system.

Knowledge-intensive product realization implies embedded intelligence; meaning that if both theoretical and practical knowledge and understanding of a subject is integrated into the design and production processes of products, this will significantly increase added value. This book presents papers accepted for the 9th Swedish Production Symposium (SPS2020), hosted by the School of Engineering, Jönköping University, Sweden, and held online on 7 & 8 October 2020 because of restrictions due to the Corona virus pandemic. The subtitle of the conference was Knowledge Intensive Product Realization in Co-Operation for Future Sustainable Competitiveness. The book contains the 57 papers accepted for presentation at the conference, and these are divided into nine sections which reflect the topics covered: resource efficient production; flexible production; virtual production development; humans in production systems; circular production systems and maintenance; integrated product and production development; advanced and optimized components, materials and manufacturing; digitalization for smart products and services; and responsive and efficient operations and supply chains. In addition, the book presents five special sessions from the symposium: development of changeable and reconfigurable production systems; smart production system design and development; supply chain relocation; management of manufacturing digitalization; and additive manufacturing in the production system. The book will be of interest to all those working in the field of knowledge-intensive product realization., Conference held online because of restrictions due to the Corona virus pandemic

Sheet metal forming tools play an important role in the manufacturing of many products. With shorter product life cycles and demand for shorter time to market for new products, the process for design and manufacturing of stamping tools becomes a critical part. Stamping dies are often designed and manufactured by smaller, specialized companies. For a tooling company, knowledge and experience is an important competitive advantage. Traditionally the design process has been characterized by being based on few key individuals with much experience and craftsmanship. To stay competitive in this market there is a need for more efficient processes, systems, tools and supports in order to become more industrialized. This paper presents results from a study of the state of practice in industry within progressive stamping tool design as well as a review of relevant literature. The design and manufacturing processes for stamping dies in six companies have been investigated through semi-structured interviews, from which the main challenges in the current state for the companies are identified. The results from the interviews was analyzed and compared to the established concepts and frameworks of methods found in the literature review. The results and analysis points in the direction of efforts needed in supporting the formalization and reuse of information and knowledge from previous tool projects and production, especially during the critical steps of tool process planning and creating the tool layout.

A rapidly growing strategy in product design and manufacture, with great potential to improve customer value, is mass-customization. The main idea is to divide the product into modules that can be shared among different product variants. This will support a wide range of options for the end customer to select among, while an internal efficiency, similar to mass-production, can be achieved. This has been a success for many companies acting on the consumer market. However, many manufacturing companies are engineer-to-order (ETO) oriented, such as original equipment suppliers (OES). They design a unique solution, often in close collaboration with other companies. The solution can then be manufactured in different quantities depending on the client’s need. For these companies, there is a strategic need for developing high quality engineering support to further utilize and exploit the information and knowledge produced during product development and to succeed with a strategy influenced by the principles of mass-customization. This has to include the implementation and management of systems enabling highly custom-engineered products to be efficiently designed and manufactured. One challenge when introducing such flexible support is to enable traceability of decisions taken, tasks executed, knowledge used and artefacts developed throughout the whole lifecycle of an individual product. In this chapter, it is shown that traceability can be achieved by introducing support for capturing, structuring and mapping between decisions and resulting outputs, such as geometrical building blocks, knowledge implemented as rules, and the argumentation for the selection, design and specification of these. Three examples are presented where the concept Design Description has been modelled based on an item-oriented, a task-oriented, and a decision-oriented perspective which show the generality of the Design Description concept. The three examples demonstrate how to use the Design Descripti