| 1. |
- Laheij, Amga, et al.
(författare)
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Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.
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| 2. |
- Laheij, Amga, et al.
(författare)
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Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients
- 2022
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Stem cell transplantation (SCT) is associated with oral microbial dysbiosis. However, long-term longitudinal data are lacking. Therefore, this study aimed to longitudinally assess the oral microbiome in SCT patients and to determine if changes are associated with oral mucositis and oral chronic graft-versus-host disease. Fifty allogeneic SCT recipients treated in two Dutch university hospitals were prospectively followed, starting at pre-SCT, weekly during hospitalization, and at 3, 6, 12, and 18 months after SCT. Oral rinsing samples were taken, and oral mucositis (WHO score) and oral chronic graft-versus-host disease (NIH score) were assessed. The oral microbiome diversity (Shannon index) and composition significantly changed after SCT and returned to pre-treatment levels from 3 months after SCT. Oral mucositis was associated with a more pronounced decrease in microbial diversity and with several disease-associated genera, such as Mycobacterium, Staphylococcus, and Enterococcus. On the other hand, microbiome diversity and composition were not associated with oral chronic graft-versus-host disease. To conclude, dysbiosis of the oral microbiome occurred directly after SCT but recovered after 3 months. Diversity and composition were related to oral mucositis but not to oral chronic graft-versus-host disease.
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| 3. |
- van Leeuwen, S. J. M., et al.
(författare)
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Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation
- 2021
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365.
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1x/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3x/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (>= 2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.
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| 4. |
- van Leeuwen, S. J. M., et al.
(författare)
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The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach
- 2023
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Ingår i: Bmc Oral Health. - 1472-6831. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score & GE; 2) or not (NON-OM).MethodsIn the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler.ResultsA different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis.ConclusionsThe salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively.
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| 5. |
- Bouchouireb, Hamza, 1991-
(författare)
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Advancing the life cycle energy optimisation methodology
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle-to-production of materials, operation of the vehicle, and end-of-life phases. This work further develops the LCEO methodology and expands its scope through three main methodological contributions which, for illustrative purposes, were applied to a vehicle sub-system design case study.An End-Of-Life (EOL) model, based on the substitution with a correction factor method, is included to estimate the energy credits and burdens that originate from EOL vehicle processing. Multiple recycling scenarios with different levels of assumed induced recyclate material property degradation were built, and their impact on the LCEO methodology's outcomes was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the inclusion of EOL modelling in the LCEO methodology can alter material use patterns and significantly effect the life cycle energy of the optimal designs.Furthermore, the previous model is expanded to enable holistic vehicle product system design with the LCEO methodology. The constrained optimisation of a vehicle sub-system, and the design of a subset of the processes which are applied to it during its life cycle, are simultaneously optimised for a minimal product system life cycle energy. In particular, a subset of the EOL processes' parameters are considered as continuous design variables with associated barrier functions that control their feasibility. The results show that the LCEO methodology can be used to find an optimal design along with its associated ideal synthetic EOL scenario. Moreover, the ability of the method to identify the underlying mechanisms enabling the optimal solution's trade-offs is further demonstrated.Finally, the functional scope of the methodology is expanded through the inclusion of shape-related variables and aerodynamic drag estimations. Here, vehicle curvature is taken into account in the LCEO methodology through its impact on the aerodynamic drag and therewith its related operational energy demand. In turn, aerodynamic drag is considered through the estimation of the drag coefficient of a vehicle body shape using computational fluid dynamics simulations. The aforementioned coefficient is further used to estimate the energy required by the vehicle to overcome aerodynamic drag. The results demonstrate the ability of the LCEO methodology to capitalise on the underlying functional alignment of the structural and aerodynamic requirements, as well as the need for an allocation strategy for the aerodynamic drag energy within the context of vehicle sub-system redesign.Overall, these methodological developments contributed to the exploration of the ability of the LCEO methodology to handle life cycle and functional trade-offs to achieve life cycle energy optimal vehicle designs.
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| 6. |
- Bouchouireb, Hamza, 1991-
(författare)
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Life Cycle Energy Optimisation: A multidisciplinary engineering design optimisation framework for sustainable vehicle development
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores how the systemic-level environmental footprint of light-duty vehicles could be reduced through integrative design using the Life Cycle Energy Optimisation (LCEO) methodology. This methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle; while complying with a set of functional constraints, thereby avoiding any sub-optimal energy demand shifts between the vehicle's different life cycle phases. This thesis further develops the LCEO methodology and expands its scope through four main methodological contributions. This work also contributes in establishing the methodology as a standalone design approach and provides guidelines for its most effective use.Initially, an End-of-Life (EOL) model, based on the substitution with a correction factor method, is included to estimate the energy credits and burdens that originate from EOL vehicle processing. Multiple recycling scenarios with varying levels of induced recyclate material property degradation were built, and their associated resulting optimal vehicle subsystem designs were compared to those associated with landfilling and incineration with energy recovery scenarios. The results show how the structural material use patterns, as well as the very mechanisms enabling the embodiment of the Life Cycle Energy (LCE) optimal designs, are impacted by taking into consideration the effect of a vehicle's EOL phase. In particular, the material intensity-space allocation trade-off was identified as a key factor in the realisation of the LCE optimal designs.This coupling existing between optimal use of material and space allocation was further explored by functionally expanding the LCEO methodology's scope to handle aerodynamic functional requirements. This involved the definition of a novel allocation strategy for the energy necessary to overcome aerodynamic drag, as well as the development of a parametrised vehicle body model that ensures that the LCE knock-on effects of aerodynamically motivated design decisions are fully accounted for at the targeted subsystem level.The expanded methodology was subsequently applied to perform the aero-structural life cycle-driven design optimisation of a vehicle subsystem, with the impact of the constitutive material's circularity potential being included through the previously developed EOL model and scenarios. The results demonstrate the significant extent of the coupling existing between a vehicle's fundamental aerodynamic shape, and a vehicle's structural material composition, including its EOL characteristics, within the LCEO context.Beyond the vehicle level implications, the LCEO methodology's position within the broader vehicle-design methodology context was further characterised by comparing its outcomes to those of the purely lightweight and purely aerodynamic approaches. It was found that the LCE optimal designs were distinctly clustered from their mono-disciplinary counterparts. They offered up to 20% energy savings over the lightweight alternatives by being, on average, larger, heavier and more aerodynamics designs; while also being shorter and lighter than the optimal aerodynamic configurations.Subsequently, a mixed integer nonlinear programming formulation of this expanded LCEO methodology was developed to include the effects of battery energy storage systems on the LCE optimal vehicle designs. In particular, the vehicle's battery size and number of such batteries needed over its life cycle were introduced as variables subject to a range and a cycle life constraint. The former is derived from the battery-capacity-to-structural-mass ratio of recent production vehicles, while the second ensures that the batteries' cycle lives are sufficient for the entirety of the vehicle's use phase. Additionally, three battery chemistries with varying characteristics were included: lithium nickel manganese cobalt oxide (NMC), lithium iron phosphate (LFP) and lithium cobalt oxide (LCO); along with an EOL recycling scenario. The results of the coupled aero-structural-battery energy storage LCE-driven design optimisations demonstrate that battery chemistry and recycling potential have a significant impact on the system's design in terms of overall LCE footprint, battery size and number, as well as aerodynamic shape. More specifically, a change in battery composition was found to lead to up to 12.5% variation in drag coefficient, while battery recycling can on average reduce a vehicle's associated LCE by 32%.Finally, elements of robust design and uncertainty quantification were included into the LCEO methodology, in order to evaluate the impact of uncertainty on the resulting LCE optimal designs. Specifically, uncertainty was introduced through the assumption that the material properties of a subset of the optimisation's candidate materials are described by statistical distributions, as opposed to a priori fixed values, thereby changing the nature of the optimisation problem from deterministic to stochastic. This change is handled through a multilevel representation hierarchy for the targeted subsystem's model, and using the Multilevel Monte Carlo (MLMC) approach in the optimisation process to evaluate the expected compliance of a given design with the transport-related functional requirements. the results demonstrate how the robust design configurations both constitute a significant departure from their deterministic counterparts and depend on the EOL scenario considered, while only incurring a marginal LCE premium. Moreover, this work also further illustrated the performance increase associated with the use of the MLMC estimator in lieu of the classical Monte Carlo one within an optimisation under uncertainty framework.Overall, the work presented in this doctoral thesis has contributed to the development of the state-of-the-art of the LCEO methodology to enable the early-stage conceptual design of more sustainable vehicle configurations, and demonstrated how the methodology is at its most effective when leveraging its cross-scalar and cross-disciplinary nature to enable integrative functional vehicle design.
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| 7. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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The inclusion of End-Of-Life modelling in the Life Cycle Energy Optimisation methodology
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work, an End-Of-Life (EOL) model is included in the Life Cycle Energy Optimisation (LCEO) methodology to account for the energy burdens and credits stemming from a vehicle’s EOL processing phase and balance them against the vehicle’s functional requirements and production and use phase energies. The substitution with a correction factor allocation method is used to model the contribution of recycling to the EOL phase’s energy. The methodology is illustrated through the optimisation of the design of a simplified vehicle sub-system. For the latter, multiple recycling scenarios with varying levels of assumed recycling induced material property degradation were built, and their impact on the vehicle sub-system’s optimal solutions was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the inclusion of EOL modelling in the LCEO methodology can significantly alter material use patterns thereby effecting the life cycle energy of the optimal designs. Indeed, the vehicle sub-system’s optimal designs associated with the recycling scenarios are on average substantially heavier, and less life cycle energy demanding, than their landfilling or incineration with energy recovery-related counterparts.
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| 8. |
- Bouchouireb, Hamza, et al.
(författare)
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The inclusion of end-of-life modelling in the life cycle energy optimisation methodology
- 2021
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Ingår i: Journal of Mechanical Design. - : ASME International. - 1050-0472 .- 1528-9001. ; 143:5
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Tidskriftsartikel (refereegranskat)abstract
- In this work, an End-Of-Life (EOL) model is included in the Life Cycle Energy Optimisation (LCEO) methodology to account for the energy burdens and credits stemming from a vehicle's EOL processing phase and balance them against the vehicle's functional requirements and production and use phase energies. The substitution with a correction factor allocation method is used to model the contribution of recycling to the EOL phase's energy. The methodology is illustrated through the optimisation of the design of a simplified vehicle sub-system. For the latter, multiple recycling scenarios with varying levels of assumed recycling induced material property degradation were built, and their impact on the vehicle sub-system's optimal solutions was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the vehicle sub-system's optimal designs are significantly dependent on the EOL scenario considered. In particular, the optimal designs associated with the recycling scenarios are on average substantially heavier, and less life cycle energy demanding, than their landfilling or incineration with energy recovery-related counterparts; thus, demonstrating how the inclusion of EOL modelling in the LCEO methodology can significantly alter material use patterns, thereby effecting the very mechanisms enabling the embodiment of the resulting life cycle energy optimal designs.
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| 9. |
- Bouchouireb, Hamza, et al.
(författare)
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The inclusion of vehicle shape and aerodynamic drag estimations within the life cycle energy optimisation methodology
- 2019
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Ingår i: Procedia CIRP. - : Elsevier. - 2212-8271 .- 2212-8271. ; 84, s. 902-907
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Tidskriftsartikel (refereegranskat)abstract
- The present work describes a widening of the scope of the Life Cycle Energy Optimisation (LCEO) methodology with the addition of shape-related design variables. They describe the curvature of a vehicle which impacts its aerodynamic drag and therewith its operational energy demand. Aerodynamic drag is taken into account through the estimation of the drag coefficient of the vehicle body shape using computational fluid dynamics simulations. Subsequently, the aforementioned coefficient is used to calculate the operational energy demand associated with the vehicle. The methodology is applied to the design of the roof of a simplified 2D vehicle model which is both mechanically and geometrically constrained. The roof is modelled as a sandwich structure with its design variables consisting of the material compositions of the different layers, their thicknesses as well as the shape variables. The efficacy of the LCEO methodology is displayed through its ability to deal with the arising functional conflicts while simultaneously leveraging the design benefits of the underlying functional alignments. On average, the optimisation process resulted in 2.5 times lighter and 4.5 times less life cycle energy-intensive free shape designs. This redesign process has also underlined the necessity of defining an allocation strategy for the energy necessary to overcome drag within the context of vehicle sub-system redesign.
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| 10. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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Towards holistic energy-efficient vehicle product system design: The case for a penalized continuous end-of-life model in the life cycle energy optimisation methodology
- 2019
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Ingår i: Proceedings of the International Conference on Engineering Design. - : Cambridge University Press. - 2220-4334 .- 2220-4342. ; 1, s. 2901-2910
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Tidskriftsartikel (refereegranskat)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle-to-production of materials, operation of the vehicle, and end-of-life phases. The present work describes the extension of the LCEO methodology to perform holistic product system optimisation. The constrained design of an automotive component and the design of a subset of the processes which are applied to it during its life cycle are simultaneously optimised to achieve a minimal product system life cycle energy. A subset of the processes of the end-of-life phase of a vehicle’s roof are modelled through a continuous formulation. The roof is modelled as a sandwich structure with its design variables being the material compositions and the thicknesses of the different layers. The results show the applicability of the LCEO methodology to product system design and the use of penalisation to ensure solution feasibility.
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