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Article ; Online: Genomic Stratification of Hematological Malignancies.

Robbe, Pauline / Schuh, Anna

HemaSphere

2023 Volume 7, Issue 6, Page(s) e902

Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Editorial
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000902
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Book ; Online: Multi-fidelity microstructure-induced uncertainty quantification by advanced Monte Carlo methods

Tran, Anh / Robbe, Pieterjan / Lim, Hojun

2023

Abstract: Quantifying uncertainty associated with the microstructure variation of a material can be a computationally daunting task, especially when dealing with advanced constitutive models and fine mesh resolutions in the crystal plasticity finite element method ...

Abstract	Quantifying uncertainty associated with the microstructure variation of a material can be a computationally daunting task, especially when dealing with advanced constitutive models and fine mesh resolutions in the crystal plasticity finite element method (CPFEM). Numerous studies have been conducted regarding the sensitivity of material properties and performance to the mesh resolution and choice of constitutive model. However, a unified approach that accounts for various fidelity parameters, such as mesh resolutions, integration time-steps, and constitutive models simultaneously is currently lacking. This paper proposes a novel uncertainty quantification (UQ) approach for computing the properties and performance of homogenized materials using CPFEM, that exploits a hierarchy of approximations with different levels of fidelity. In particular, we illustrate how multi-level sampling methods, such as multi-level Monte Carlo (MLMC) and multi-index Monte Carlo (MIMC), can be applied to assess the impact of variations in the microstructure of polycrystalline materials on the predictions of homogenized materials properties. We show that by adaptively exploiting the fidelity hierarchy, we can significantly reduce the number of microstructures required to reach a certain prescribed accuracy. Finally, we show how our approach can be extended to a multi-fidelity framework, where we allow the underlying constitutive model to be chosen from either a phenomenological plasticity model or a dislocation-density-based model.
Keywords	Condensed Matter - Materials Science ; Statistics - Applications
Subject code	621
Publishing date	2023-02-06
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Multi-fidelity uncertainty quantification for homogenization problems in structure-property relationships from crystal plasticity finite elements

Tran, Anh / Robbe, Pieterjan / Rodgers, Theron / Lim, Hojun

2023

Abstract: Crystal plasticity finite element method (CPFEM) has been an integrated computational materials engineering (ICME) workhorse to study materials behaviors and structure-property relationships for the last few decades. These relations are mappings from the ...

Abstract	Crystal plasticity finite element method (CPFEM) has been an integrated computational materials engineering (ICME) workhorse to study materials behaviors and structure-property relationships for the last few decades. These relations are mappings from the microstructure space to the materials properties space. Due to the stochastic and random nature of microstructures, there is always some uncertainty associated with materials properties, for example, in homogenized stress-strain curves. For critical applications with strong reliability needs, it is often desirable to quantify the microstructure-induced uncertainty in the context of structure-property relationships. However, this uncertainty quantification (UQ) problem often incurs a large computational cost because many statistically equivalent representative volume elements (SERVEs) are needed. In this paper, we apply a multi-level Monte Carlo (MLMC) method to CPFEM to study the uncertainty in stress-strain curves, given an ensemble of SERVEs at multiple mesh resolutions. By using the information at coarse meshes, we show that it is possible to approximate the response at fine meshes with a much reduced computational cost. We focus on problems where the model output is multi-dimensional, which requires us to track multiple quantities of interest (QoIs) at the same time. Our numerical results show that MLMC can accelerate UQ tasks around 2.23x, compared to the classical Monte Carlo (MC) method, which is widely known as the ensemble average in the CPFEM literature.
Keywords	Mathematics - Numerical Analysis ; Condensed Matter - Materials Science
Subject code	518
Publishing date	2023-10-26
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Factors affecting the manual linking of clinical progress notes to problems in daily clinical practice: A retrospective quantitative analysis and cross sectional survey.

Cillessen, Felix / de Vries Robbé, Pieter / Bor, Hans / Biermans, Marion

Health informatics journal

2021 Volume 27, Issue 2, Page(s) 14604582211007534

Abstract: This cross sectional study examines how patient characteristics, doctor characteristics, and doctors' education and attitudes affect the extent to which doctors link progress notes to clinical problems. The independent effects of patient characteristics ... ...

Abstract	This cross sectional study examines how patient characteristics, doctor characteristics, and doctors' education and attitudes affect the extent to which doctors link progress notes to clinical problems. The independent effects of patient characteristics on the linking of notes was examined with a mixed model logistic regression. The effects of doctor characteristics and doctors' education and attitudes on the link ratio was analyzed with univariate analysis of variance. A survey was used to obtain arguments and attitudes on linking notes. For "patient characteristics", the odds of linking increased with an increase in the number of problems or hospital days, decreased, with an increase in the number of involved doctors, medical specialties or the number of notes. For "doctor characteristics", the link ratio increased with more work experience. For "doctors' education and attitudes", the link ratio increased with more familiarity in linking notes and belief in the added value of problem oriented charting. "Overview" was the most cited reason for linking; "I don't know how" the most cited reason for not linking. There is a huge variation within and between all disciplines. Important arguments, for and against, are found. Recommendations for policymakers and medical leadership are given to maximize the benefits.
MeSH term(s)	Cross-Sectional Studies ; Electronic Health Records ; Humans ; Physicians ; Retrospective Studies ; Surveys and Questionnaires
Language	English
Publishing date	2021-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2213115-2
ISSN	1741-2811 ; 1460-4582
ISSN (online)	1741-2811
ISSN	1460-4582
DOI	10.1177/14604582211007534
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Book ; Online: The multifaceted nature of uncertainty in structure-property linkage with crystal plasticity finite element model

Tran, Anh / Robbe, Pieterjan / Wildey, Tim / Zapiain, David Montes de Oca / Lim, Hojun

2023

Abstract: Uncertainty quantification (UQ) plays a critical role in verifying and validating forward integrated computational materials engineering (ICME) models. Among numerous ICME models, the crystal plasticity finite element method (CPFEM) is a powerful tool ... ...

Abstract	Uncertainty quantification (UQ) plays a critical role in verifying and validating forward integrated computational materials engineering (ICME) models. Among numerous ICME models, the crystal plasticity finite element method (CPFEM) is a powerful tool that enables one to assess microstructure-sensitive behaviors and thus, bridge material structure to performance. Nevertheless, given its nature of constitutive model form and the randomness of microstructures, CPFEM is exposed to both aleatory uncertainty (microstructural variability), as well as epistemic uncertainty (parametric and model-form error). Therefore, the observations are often corrupted by the microstructure-induced uncertainty, as well as the ICME approximation and numerical errors. In this work, we highlight several ongoing research topics in UQ, optimization, and machine learning applications for CPFEM to efficiently solve forward and inverse problems.
Keywords	Condensed Matter - Materials Science ; Statistics - Applications
Publishing date	2023-01-26
Publishing country	us
Document type	Book ; Online
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Article: What establishes an excellent nurse? A focus group and Delphi panel approach.

Paans, Wolter / Robbe, Patricia / Wijkamp, Inge / Wolfensberger, Marca V C

BMC nursing

2017 Volume 16, Page(s) 45

Abstract: Background: Over the past few years, the complexity of the health care system in which nurses are required to practice has increased considerably, magnifying the need for excellent professionals with a specific set of knowledge, skills and attitudes. ... ...

Abstract	Background: Over the past few years, the complexity of the health care system in which nurses are required to practice has increased considerably, magnifying the need for excellent professionals with a specific set of knowledge, skills and attitudes. However, the characteristics that distinguish an excellent nurse have not yet been clarified. The aim of this study was to determine nurses' perspectives regarding characteristics associated with an excellent nurse in order to elicit a conceptual profile. Method: A focus group design followed by Delphi panel content validation was utilized. Information regarding nurses' perspectives was derived from six focus group discussions comprising 19 nurses involved in hospital practice and 24 nurses with experience in mental health care. The analysis of the focus group discussions resulted in nine domains whereby content validity was achieved with contributions from a Delphi panel survey with 26 professionals. Results: As determined by the survey, a combination of these specified aspects characterize an excellent nurse: analytical, communicative, cooperative, coordinating, disseminates knowledge, empathic, evidence-driven, innovative and introspective. Conclusion: Determining what establishes an excellent nurse according to experienced nurses is valuable as this information can influence the broadening curriculum for educating future nurses to meet the needs in the professional field, contributing to the quality of care. This conceptual profile can be used as a reference guide for supervisors and professionals to personally improve their clinical practice as well as for education.
Language	English
Publishing date	2017-08-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2091496-9
ISSN	1472-6955
ISSN	1472-6955
DOI	10.1186/s12912-017-0239-x
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Article ; Online: Dual role of YM1+ M2 macrophages in allergic lung inflammation.

Draijer, Christina / Robbe, Patricia / Boorsma, Carian E / Hylkema, Machteld N / Melgert, Barbro N

Scientific reports

2018 Volume 8, Issue 1, Page(s) 5105

Abstract: Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we ... ...

Abstract	Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation during and after development of allergic lung inflammation by treating with cynaropicrin, a galectin-3 pathway inhibitor. Mice that were treated with this inhibitor of M2 polarisation during induction of allergic inflammation developed less severe eosinophilic lung inflammation and less collagen deposition around airways, while the airway α-smooth muscle actin layer was unaffected. When we treated with cynaropicrin after induction of inflammation, eosinophilic lung inflammation and collagen deposition were also inhibited though to a lesser extent. Unexpectedly, both during and after induction of allergic inflammation, inhibition of M2 polarisation resulted in a shift towards neutrophilic inflammation. Moreover, airway hyperresponsiveness was worse in mice treated with cynaropicrin as compared to allergic mice without inhibitor. These results show that M2 macrophages are associated with remodeling and development of eosinophilic lung inflammation, but prevent development of neutrophilic lung inflammation and worsening of airway hyperresponsiveness. This study suggests that macrophages contribute to determining development of eosinophilic or neutrophilic lung inflammation in asthma.
MeSH term(s)	Animals ; Asthma/drug therapy ; Asthma/immunology ; Asthma/pathology ; Cell Polarity/drug effects ; Female ; Lactones/therapeutic use ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/pathology ; Mice, Inbred BALB C ; Pneumonia/drug therapy ; Pneumonia/immunology ; Pneumonia/pathology ; Respiratory Hypersensitivity/drug therapy ; Respiratory Hypersensitivity/immunology ; Respiratory Hypersensitivity/pathology ; Sesquiterpenes/therapeutic use
Chemical Substances	Lactones ; Sesquiterpenes ; cynaropicrin (M9233789I9)
Language	English
Publishing date	2018-03-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-23269-7
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Article ; Online: Healthy worker survivor analysis in an occupational cohort study of Dutch agricultural workers.

Spierenburg, E A J / Smit, L A M / Heederik, D / Robbe, P / Hylkema, M N / Wouters, I M

International archives of occupational and environmental health

2015 Volume 88, Issue 8, Page(s) 1165–1173

Abstract: Objectives: High microbial exposures in farmers and agricultural workers are associated with less atopy. Although it has been speculated that healthy worker survival could be an explanation, this has not been studied so far. Therefore, we investigated ... ...

Abstract	Objectives: High microbial exposures in farmers and agricultural workers are associated with less atopy. Although it has been speculated that healthy worker survival could be an explanation, this has not been studied so far. Therefore, we investigated the presence of healthy worker survival in a five-year follow-up study of an occupational cohort of Dutch farmers and agricultural industry (company) workers. Methods: We compared baseline demographic characteristics, respiratory health, atopy and endotoxin exposure of 259 workers followed up with 124 workers lost to follow-up. Additionally, baseline health status of 31 participants who had changed to lower exposure jobs at follow-up was compared to those with similar or higher exposure jobs at follow-up. Results: In general, no major healthy worker survival effect was found. Nonetheless, small differences were observed between subjects included in follow-up and those lost to follow-up. Those lost to follow-up were older, had a lower peak expiratory flow, and were less often raised on a farm. Company workers lost to follow-up with a farm childhood had more often self-reported allergy, but this was not observed for subjects with atopic sensitization or other respiratory symptoms. No differences were found for any of the studied characteristics in participants with lower exposure at follow-up compared to participants with similar or higher exposure at follow-up. Conclusions: No major healthy worker survival is present in this organic dust exposed cohort. Differences between participants lost to follow-up and participants included in follow-up with regard to health characteristics are small and unlikely to explain the previously reported inverse associations between endotoxin exposure and atopy.
MeSH term(s)	Adult ; Agricultural Workers' Diseases/microbiology ; Agricultural Workers' Diseases/mortality ; Agriculture ; Cohort Studies ; Endotoxins/analysis ; Endotoxins/toxicity ; Female ; Follow-Up Studies ; Healthy Worker Effect ; Humans ; Hypersensitivity, Immediate/microbiology ; Hypersensitivity, Immediate/mortality ; Lost to Follow-Up ; Male ; Middle Aged ; Netherlands/epidemiology ; Occupational Exposure/adverse effects ; Occupational Exposure/analysis ; Survival Analysis ; Time Factors
Chemical Substances	Endotoxins
Language	English
Publishing date	2015-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	129038-1
ISSN	1432-1246 ; 0340-0131 ; 0367-9977
ISSN (online)	1432-1246
ISSN	0340-0131 ; 0367-9977
DOI	10.1007/s00420-015-1047-9
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Article ; Online: Long-term follow-up of 415 patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide-based chemoimmunotherapy in the frontline ADMIRE and ARCTIC trials: A comprehensive assessment of prognostic factors.

Allsup, David John / Craig, Zoe / Cairns, David / Howard, Dena / Hockaday, Anna / Bloor, Adrian / Soe, Zarni / Pepper, Christopher / Gattei, Valter / Zucchetto, Antonella / Robbe, Pauline / Clifford, Ruth / Schuh, Anna / Munir, Talha / Rawstron, Andrew / Hillmen, Peter

American journal of hematology

2022 Volume 97, Issue 5, Page(s) E168–E171

MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide ; Follow-Up Studies ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Prognosis ; Rituximab ; Treatment Outcome ; Vidarabine/analogs & derivatives
Chemical Substances	Rituximab (4F4X42SYQ6) ; Cyclophosphamide (8N3DW7272P) ; Vidarabine (FA2DM6879K) ; fludarabine (P2K93U8740)
Language	English
Publishing date	2022-02-12
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26483
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Article ; Online: Targeted deep sequencing reveals clinically relevant subclonal IgHV rearrangements in chronic lymphocytic leukemia.

Stamatopoulos, B / Timbs, A / Bruce, D / Smith, T / Clifford, R / Robbe, P / Burns, A / Vavoulis, D V / Lopez, L / Antoniou, P / Mason, J / Dreau, H / Schuh, A

Leukemia

2017 Volume 31, Issue 4, Page(s) 837–845

Abstract: The immunoglobulin heavy-chain variable region gene (IgHV) mutational status is considered the gold standard of prognostication in chronic lymphocytic leukemia (CLL) and is currently determined by Sanger sequencing that allows the analysis of the major ... ...

Abstract	The immunoglobulin heavy-chain variable region gene (IgHV) mutational status is considered the gold standard of prognostication in chronic lymphocytic leukemia (CLL) and is currently determined by Sanger sequencing that allows the analysis of the major clone. Using next-generation sequencing (NGS), we sequenced the IgHV gene from two independent cohorts: (A) 270 consecutive patient samples obtained at diagnosis and (B) 227 patients from the UK ARCTIC-AdMIRe clinical trials. Using complementary DNA from purified CD19+CD5+ cells, we demonstrate the presence of multiple rearrangements in independent experiments and showed that 24.4% of CLL patients express multiple productive clonally unrelated IgHV rearrangements. On the basis of IgHV-NGS subclonal profiles, we defined five different categories: patients with (a) multiple hypermutated (M) clones, (b) 1 M clone, (c) a mix of M-unmutated (UM) clones, (d) 1 UM clone and (e) multiple UM clones. In population A, IgHV-NGS classification stratified patients into five different subgroups with median treatment-free survival (TFS) of >280(a), 131(b), 94(c), 29(d), 15(e) months (P<0.0001) and a median OS of >397(a), 292(b), 196(c), 137(d) and 100(e) months (P<0.0001). In population B, the poor prognosis of multiple UM patients was confirmed with a median TFS of 2 months (P=0.0038). In conclusion, IgHV-NGS highlighted one quarter of CLL patients with multiple productive IgHV subclones and improves disease stratification and raises important questions concerning the pre-leukemic cellular origin of CLL.
MeSH term(s)	B-Lymphocytes/metabolism ; Biomarkers ; Clonal Evolution/genetics ; Female ; Genes, Immunoglobulin Heavy Chain ; High-Throughput Nucleotide Sequencing ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Variable Region/genetics ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/mortality ; Male ; Mutation ; Phenotype ; Prognosis ; Proportional Hazards Models
Chemical Substances	Biomarkers ; Immunoglobulin Heavy Chains ; Immunoglobulin Variable Region
Language	English
Publishing date	2017-04
Publishing country	England
Document type	Journal Article
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/leu.2016.307
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