Finding Perfection in Imperfection:: A Case Study of Adding Value by Design in Circular Economy

The United States' manufacturing industry generates approximately 7.6 billion tons of non- hazardous solid waste each year, a significant portion of which is either recyclable or reusable. Emerging ecosystem concepts such as cradle-to-cradle, design for disassembly, sustainable manufacturing, and most recently circular economy, are promoting the reusing or recycling of non-hazardous industrial waste. Empirical evidence suggests that there are significant economic, environmental, and social benefits to reusing industrial waste rather than recycling it. This paper presents, discusses and synthesis five speculative case studies in designing exterior building skins using standard automobile stamping by-products. The goal of the design experiment was to transform the linear approach in making building components, particularly, exterior metal skins and cladding systems, to a closed-loop approach, which ensures multi-dimensional economic, social, and environmental benefits. The results of the study are expected to aid in the reduction of energy used for extracting new materials and change the focus of the current waste management practices in the manufacturing industry from conventional recycling to creative reuse. The imperfection of the manufacturing industrial waste despite optimization measures, and the aging of zinc (patina) can both be transformed into novel unconventional architectural products

Activating Circular Economy through Industrial Symbiosis: A Case Study of a Novel Modular Living Wall System

This research investigates the potentials of designing for sustainability, specifically “design for reuse” using a systematic by-product of industrial production processes, in a mutual exchange known as industrial symbiosis (IS) for a more circular economy (CE). CE seeks to change traditional methods of take, make, waste to eliminate the concept of waste after consumers use goods. This study focuses on fostering CE through IS between the automotive and the building and construction industries through creative architectural reuse. Previous attempts at IS between both industries have involved reusing materials such as end-of-life metal, tires and plastics but none have explored the reuse of prompt sheet metal cutouts (Offal) from automotive assembly processes. A workflow of three parts is presented in this manuscript-style dissertation. The first manuscript presents “design for reuse” modules made from Offal. Experimental studies were conducted for four unique geometries to determine their cooling effect in two seasons and resource efficiency. The second manuscript presents a novel modular living wall system (MLWS) made with a module from Manuscript 1. Experimental data from measurement campaigns during four seasons (winter, spring, summer and fall) was used to calibrate 24-hour simulations of thermal performance in ENVI-met. Life cycle analyses (LCA) were also used to determine economic and environmental impacts. The third manuscript presented a techno-economic analysis comparing the novel MLWS to traditional living wall systems (LWS). Analysis of the novel MLWS was carried out through LCA and available data for parameters such as fuel consumption, electricity, net primary energy, and product costs. This dissertation investigates the potentials of creatively reusing industrial byproducts as feedstock in building and construction products through a case study. The case study was approached by studying module units, then a system which provided data for simulation at a bigger scale. Findings include a new method to test the performance of LWS; a new methodology to initiate reuse for solid non-hazardous industrial waste streams and opportunities to investigate frameworks for other industrial waste streams. Activating CE through IS could provide economic, environmental and technical benefits. Findings contribute to operational data required by decision and policy makers to promote circularity

Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial

BACKGROUND: Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). METHODS: KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1-21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT02576977, and it is closed for accrual. FINDINGS: Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8\ub71 months (IQR 4\ub75-10\ub79). Median progression-free survival was 5\ub76 months (95% CI 3\ub77-7\ub75) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8\ub74 months (5\ub79-not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37-58) versus 60% (49-69) at 6 months (hazard ratio [HR] 1\ub753; 95% CI 1\ub705-2\ub722; p=0\ub798). Median overall survival was not reached (95% CI 12\ub79-not reached) versus 15\ub72 months (12\ub77-not reached; HR 1\ub761; 95% CI 0\ub791-2\ub785; p=0\ub795); overall survival estimates at 6 months were 82% (95% CI 74-88) versus 90% (82-95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens-Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. INTERPRETATION: The results from this unplanned, FDA-requested, interim analysis showed that the benefit-risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA)