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The demand for delivering product variety has been increasing. Increased product variety caused by product customization, personalization, evolution and changes in their manufacturing systems. Variety allows manufacturers to satisfy a wide range of customer requirements, but it can also be a major contributing factor to increased complexity of assembly. Complexity is generally believed to be one of the main causes of the present challenges in manufacturing systems such as lengthy and costly design processes, higher life cycle costs and the existence of numerous failure modes. Complex assembly systems are costly to implement, run, control and maintain. Assessing complexity of assembly helps guides designers in creating assembly-oriented product designs and following steps to reduce and manage sources of assembly complexity. On the other hand, reducing complexity of assembly helps lower assembly cost and time, improves productivity and quality and increases profitability and competitiveness. The complexity of assembly should be assessed by considering both products and their assembly systems. In this paper, a structural classification coding scheme has been used to measure assembly systems complexity. It considers the inherent structural complexity of typical assembly equipment. The derived assembly systems complexity accounts for the number, diversity and information content within each class of the assembly system modules. A domestic appliance drive assembly system is used to demonstrate the use of the classification code to calculate the assembly system complexity. The developed complexity metrics can be used by designers as decision support tools to compare and rationalize various automated assembly systems alternatives and select the design that meets the requirements while reducing potential assembly complexity and associated cost. [ABSTRACT FROM AUTHOR]

This paper presents data analysis and model generation techniques for reverse engineering rotary components such as shafts and rotary dies. Existing reverse engineering techniques create a computer-aided design model from point cloud data that are a mathematical ‘best fit’, but this may be an inaccurate representation due to noise contained in the model. Also, rotary components have their own set of design parameters and reverse engineering design challenges. For several rotary applications, the point cloud data go through a series of transformations (such as transforming the points from a rotational to a planar representation) in order to extract the relevant information, and then a ‘healing’ process is performed to modify critical geometry and dimensions. To meet these challenges, a systematic approach is adopted in a comprehensive manner to extract the relevant information and transform it into relevant design knowledge. Several practical examples are presented that highlight the issues, the reverse engineering methodology, and how these techniques provide a platform for any subsequent design modifications and the component manufacture. [ABSTRACT FROM AUTHOR]

Supply chain management (SCM) presents significant opportunities for improving profit margins and reducing cost. It encompasses functional and geographical integration as well as integration of tactical and operational decisions. The functional integration aspects involve purchasing, manufacturing, and logistics within the company and across the supply chain. A supply chain design framework has been developed including linear/mixed integer multi-criteria optimization models for determining the identified supply chain design parameters. The selection of suppliers, determination of production quantities, inventory locations and sizes, selection of transportation method and transported quantities in a multi-stage, multi-level supply chain are investigated. Additional criteria including first-time quality (FTQ) and suppliers on-time delivery risk with and without allowing splitting of customer demand between suppliers are considered. An example of typical automotive power train supply chain design and decision issues is used to illustrate the effect of various factors. [ABSTRACT FROM AUTHOR]

A design analysis approach is developed for improving the stability of dynamic systems subject to non-conservative forces. It combines genetic algorithms, sequential quadratic programming (SQP), and dynamic mode tracking (DMT). The proposed approach automatically optimizes the stability criterion and is applicable to rotor dynamics, wind turbine dynamics, aeronautics, and ground vehicle dynamics. The Routh-Hurwitz criterion has traditionally been used for determining the stability characteristics of these dynamic systems. In the conventional trial and error approaches, designers iteratively change the values of the design variables and reanalyze until an acceptable stability characteristic is achieved. This is both time-consuming and tedious. The proposed approach automates the design/analysis cycle by using the DMT technique to identify the modes; then, the SQP algorithm determines the stability criterion; and finally a genetic algorithm is applied to optimize design variables. The proposed integrated approach has been tested and evaluated numerically using a linearized car-trailer model with three degrees of freedom and the results demonstrate its feasibility and efficacy. The performed parametric sensitivity analysis revealed that the geometric parameters have a much greater influence on the lateral stability of the vehicle systems, compared with inertia parameters and torsional spring stiffness coefficients. [ABSTRACT FROM AUTHOR]

This paper presents a new methodology for designing modular products taking into account assembly complexity and Design for Assembly. DFA encourages components integration to reduce assembly time, while modularity promotes partitioning and decomposition of product architectures into components and modules to facilitate interchangeability. A product granularity level determines the details of its architecture. The best product architecture granularity level, and size and number of product modules are determined using Cladistics – a hierarchical classification tool – along with the Design Structure Matrix (DSM) and assembly insertion and handling complexity indices. A case study using a DC vibration motor is used to demonstrate the application of the presented methodology. It is observed that increasing assembly complexity promotes coarser product architecture granularity and more modularity results in finer product granularity. Use of the presented design methodology achieves the best trade-off between products modularity and integration. [ABSTRACT FROM AUTHOR]

A new extension of the stochastic linear quadratic Gaussian (LQG) regulator problem is developed and used for the design of new suboptimal cross-coupling controllers for machine tool drives. This new extension allowed us to combine both the drive and the cutting dynamics into a unified model driven by the static and the dynamic portions of the cutting force. The dynamic portion of the cutting force is considered as a stochastic random process in end milling contouring processes. The outputs of the axes are corrected by the cutting tool deflections which result from the cutting force-workpiece resistance interactive dynamics. Most importantly, the LQG extension developed here is directly applicable to the design and optimization of centralized, decentralized, and hierarchical machine tool controllers that have previously appeared in the literature. This is possible because our extension allows the assignment of a different control structure for each control input even if more than one control input are contributing to the same axis. Furthermore, the method admits each controller to function in any chosen subset of the available measurements. Thus, it provides us with a powerful means for designing any of the above-mentioned controllers using the same approach. The results of our suboptimal cross-coupling controllers were magnificent when compared to the commercially available positioning controllers. [ABSTRACT FROM AUTHOR]

Summary: Background: Significantly more patients with moderate‐to‐severe plaque psoriasis treated with the interleukin (IL)‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab in the IXORA‐R head‐to‐head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. Objectives: To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to week 24. Methods: IXORA‐R enrolled adults with moderate‐to‐severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran–Mantel–Haenszel test stratified by pooled site. Time‐to‐first‐event comparisons were performed using Kaplan–Meier analysis, and P‐values were generated using adjusted log‐rank tests stratified by treatment group. Cumulative days at clinical and patient‐reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). Results: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference −2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. Conclusions: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate‐to‐severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab. What is already known about this topic?Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A.In the 12‐week report of the IXORA‐R study, ixekizumab demonstrated significantly higher efficacy at early timepoints than the IL‐23p19 inhibitor guselkumab, with more patients achieving 100% improvement in Psoriasis Area and Severity Index (PASI 100) and improved quality of life as early as week 4. What does this study add?Patients on ixekizumab vs. guselkumab achieved similar levels of skin clearance and superior efficacy in the resolution of nail psoriasis at week 24.Patients on ixekizumab vs. guselkumab had a greater cumulative benefit, with more days at PASI 90 and 100, more days when psoriasis did not impact their quality of life, and more itch‐free days.The safety profiles of both drugs were consistent with those in previous studies. Linked Comment: Puig. Br J Dermatol 2021; 184:992–993. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with psoriasis value rapid and complete skin clearance. No head‐to‐head studies have focused on early responses to interleukin (IL)‐17 vs. IL‐23 inhibitors. Objectives: To compare early and complete skin clearance by the IL‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab. Methods: IXORA‐R, a 24‐week, randomized, double‐blinded study, enrolled adults with moderate‐to‐severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran–Mantel–Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. Results: In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. Conclusions: Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate‐to‐severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL‐23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate‐to‐severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response.Clinical trial data and systematic reviews have suggested that IL‐17 inhibitors can improve a patient's psoriasis more rapidly than IL‐23 inhibitors. What does this study add? The head‐to‐head study design directly compares the efficacy and speed of response of ixekizumab and the IL‐23 inhibitor guselkumab in moderate‐to‐severe plaque psoriasis.The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12.The safety profile of ixekizumab was consistent with previous studies.Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab. Linked Comment:Veysey. Br J Dermatol 2020; 182:1321–1322. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Long‐term management of moderate‐to‐severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment. Objective: To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis. Methods: This single‐arm, open‐label study (UNCOVER‐J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160‐mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ≤50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks. Results: At Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment‐emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period. Conclusion: In patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment. [ABSTRACT FROM AUTHOR]

Background: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24‐ and 52‐week findings of an open‐label, phase 3 trial (UNCOVER‐J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. Objective: To assess the long‐term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. Methods: These subgroup analyses were of a partial population of patients from UNCOVER‐J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment‐emergent adverse events and adverse events of special interest. Results: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. Conclusion: These findings suggest that ixekizumab can be an effective long‐term treatment option for erythrodermic or generalized pustular psoriasis. Linked article: This article is commented on G. Egawa et al., p. 259 in this issue. To view this article visit https://doi.org/10.1111/jdv.15416 [ABSTRACT FROM AUTHOR]

Summary: 银屑病是一种皮肤病,会导致全身皮肤出现红色、鳞屑和瘙痒的斑块。 它影响着全球约 1.25 亿人。除了导致生活质量下降外,更广泛的银屑病往往会影响内在健康。过去几年开发的新药经常可以帮助银屑病患者实现完全清除皮损,并改善整体健康状况。 其中两种药物是 ixekizumab (IXE) 和 guselkumab (GUS)。然而,IXE 和 GUS 的工作方式不同,之前的一些研究表明,IXE 可能比 GUS 起效更快。 在这项研究中,来自美国和加拿大的研究人员对这些药物进行了直接对比测试,测量了开始用药后头 12 周的清除速度和皮肤完全清除率。 这项研究中的人接受了 IXE 或 GUS。12 周后,接受 IXE 治疗的人皮损完全清除者所占比例比接受 GUS 治疗的人高 16%(使用 IXE 的人为 41%,使用 GUS 的人为 25%)。 无论使用一周后皮肤清除率达 50% 的人数,还是使用两周后皮肤清除率达 75% 的人数,IXE 都比 GUS 多。与 GUS 相比,IXE 对瘙痒、皮肤疼痛和生活质量的改善也更快。IXE 和 GUS 出现严重副作用的患者数量相似。 总体而言,与使用 GUS 的患者相比,使用 IXE 的银屑病患者皮肤清除干净的速度更快,也更为迅速感觉好转。 本摘要涉及研究: 来自一项随机分配、双盲试验的 Ixekizumab 与 Guselkumab 治疗中度至重度斑块型银屑病患者的直接比较: 12 周疗效、安全性和应答速度 Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a skin disease that causes red, scaly and itchy patches of skin all over the body. It affects about 125 million people worldwide. As well as causing decreased quality of life, more widespread psoriasis often affects internal health. New drugs developed in the last few years often help people with psoriasis to achieve completely clear skin, and improve overall health. Two of these drugs are ixekizumab (IXE) and guselkumab (GUS). IXE and GUS work in different ways, however, and some prior research showed that IXE may work faster than GUS. In this study, researchers from the U.S.A. and Canada tested these drugs head‐to‐head, measuring speed of clearance and complete skin clearance rates over the first 12 weeks after starting drug. People in this study received either IXE or GUS. After 12 weeks, completely clear skin was achieved by 16% more people if they were treated with IXE compared to GUS (41% of people who took IXE versus 25% of people who took GUS). More people on IXE than GUS had 50% clearer skin after just one week and 75% clearer skin after two weeks. Itching, skin pain, and quality of life also improved faster with IXE compared to GUS. The number of patients with serious side effects was similar for IXE and GUS. Overall, people with psoriasis who take IXE may get clear skin faster and feel better more quickly than people who take GUS. This is a summary of the study: A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]