| 1. |
- Hagenbeek, FA, et al.
(author)
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Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 39-
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Journal article (peer-reviewed)abstract
- Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
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| 2. |
- Caspers, I. A., et al.
(author)
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Effect of preoperative chemotherapy on the histopathological classification of gastric cancer
- 2024
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In: Gastric Cancer. - : Springer. - 1436-3291 .- 1436-3305. ; 27, s. 102-109
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Journal article (peer-reviewed)abstract
- Background: In the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment.Methods: Histological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and "other" subtypes of GC were analyzed.Results: In total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and "other" subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the "other" subtypes, respectively.Conclusion: Our results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible.
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| 5. |
- Caspers, Irene A., et al.
(author)
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The impact of sex on treatment and outcome in relation to histological subtype in patients with resectable gastric cancer : Results from the randomized CRITICS trial
- 2024
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In: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 129:4, s. 734-744
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Journal article (peer-reviewed)abstract
- Background and ObjectiveThis study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC).MethodsA post-hoc analysis of the CRITICS-trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy-related toxicity and compliance were compared.ResultsData from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor-positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes.ConclusionsPositive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.
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| 6. |
- Caspers, IA, et al.
(author)
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Risk Factors for Metachronous Isolated Peritoneal Metastasis after Preoperative Chemotherapy and Potentially Curative Gastric Cancer Resection: Results from the CRITICS Trial
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:18
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Journal article (peer-reviewed)abstract
- Gastric cancer (GC) patients at high risk of developing peritoneal metastasis (PM) as a single site of metastasis after curative treatment may be candidates for adjuvant prophylactic strategies. Here we investigated risk factors for metachronous isolated PM in patients who were treated in the CRITICS trial (NCT00407186). Univariable and multivariable analyses on both metachronous isolated PM and ‘other events’, i.e., (concurrent) distant metastasis, locoregional recurrence or death, were performed using a competing risk model and summarized by cumulative incidences. Isolated PM occurred in 64 of the 606 (11%) included patients. Diffuse or mixed histological subtype, ypT4 tumor stage and LNhigh (ypN3 lymph node stage or a lymph node ratio >20%) were independent risk factors for isolated PM in both univariable and multivariable analyses. Likewise, LNhigh was an independent risk factor for ‘other events’. Patients with tumors who were positive for all three independent risk factors had the highest two-year cumulative incidence of 43% for isolated PM development. In conclusion, diffuse or mixed histological subtype, ypT4 and LNhigh were identified as independent risk factors for isolated PM in patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors may identify a subgroup that may benefit from PM-preventing treatment strategies.
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| 10. |
- Gavriilidou, A., et al.
(author)
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Reconciling transfer synchronization and service regularity : real-time control strategies using passenger data
- 2019
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In: Transportmetrica A. - : Taylor and Francis Ltd.. - 2324-9935 .- 2324-9943. ; 15:2, s. 215-243
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Journal article (peer-reviewed)abstract
- Real-time holding control strategies are implemented, among other reasons, in order to protect transfers. In the context of high-frequency services, there is a need to reconcile between striving for single-line regularity and synchronizing inter-line arrivals. Their operationalization depends on the predictions regarding passenger flows across the network. We examine the influence of real-time passenger data on the performance of transfer synchronization control. To this end, we develop two real-time transfer synchronization controllers which make use of different passenger data sources. The controllers differ in their assumptions concerning capacity constraints as well as on-board crowding conditions. The results show that each transferring passenger saves on average 2–10 min thanks to the proposed strategy, while on-board passengers experience a delay of 1–2 min each in most cases. The highest time saving per transferring passenger is obtained when the demand level is low and the controller opts for synchronizing more frequently. Highlights Rule-based holding controller selects transfer synchronization or line regularity The impact of different passenger data on controller performance is investigated On-board crowding conditions are considered by the real-time controller On-board occupancy is the most valuable real-time passenger data source.
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| 13. |
- Slagter, AE, et al.
(author)
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Triplet Chemotherapy with Cisplatin versus Oxaliplatin in the CRITICS Trial: Treatment Compliance, Toxicity, Outcomes and Quality of Life in Patients with Resectable Gastric Cancer
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:12
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Journal article (peer-reviewed)abstract
- (1) Background: Perioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Based on studies in patients with metastatic gastric cancer, oxaliplatin has replaced cisplatin in the curative setting as well. However, evidence to prefer oxaliplatin over cisplatin in the curative setting is limited. (2) Methods: We compared patient-related and tumor-related outcomes for cisplatin versus oxaliplatin in patients with resectable gastric cancer treated with perioperative chemotherapy in the CRITICS trial. (3) Results: Preoperatively, 632 patients received cisplatin and 149 patients received oxaliplatin. Preoperative severe toxicity was encountered in 422 (67%) patients who received cisplatin versus 89 (60%) patients who received oxaliplatin (p = 0.105). Severe neuropathy was observed in 5 (1%) versus 6 (4%; p = 0.009) patients, respectively. Postoperative severe toxicity occurred in 109 (60%) versus 26 (51%) (p = 0.266) patients; severe neuropathy in 2 (1%) versus 2 (4%; p = 0.209) for patients who received cisplatin or oxaliplatin, respectively. Diarrhea impacted the quality of life more frequently in patients who received oxaliplatin compared to cisplatin. Complete or near-complete pathological response was achieved in 94 (21%) versus 16 (15%; p = 0.126) patients who received cisplatin or oxaliplatin, respectively. Overall survival was not significantly different in both groups (p = 0.300). (4) Conclusions: Both cisplatin and oxaliplatin are legitimate options as part of systemic treatment in patients with resectable gastric cancer.
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| 15. |
- Susilo, Yusak O., et al.
(author)
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Implementing a Behavioural Pilot Survey for the Stage-based Study of the whole Journey Traveller Experience
- 2015
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In: Transportation Research Procedia. - : Elsevier. - 2352-1465.
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Conference paper (peer-reviewed)abstract
- The European project METPEX aims to develop an evaluation tool for the whole journey experience from the passenger viewpoint. A pilot survey has been implemented to help identify what kind of information should be collected to this effect. Five categories of variables were identified and tested: individual attributes, contextual variables, attitudes, travel experience and satisfaction aspects. Administering the pilot survey resulted in a total of 554 interviews in eight different European cities. The gained experience was supplemented by consultation with 45 different stakeholders that reviewed the tool. Potentialities and shortcomings that emerged from these assessment activities are discussed.
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| 19. |
- Woodcock, A., et al.
(author)
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Measuring quality across the whole journey
- 2014
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In: Contemporary Ergonomics and Human Factors 2014. - : Taylor & Francis. - 9781138026353 ; , s. 316-323
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Conference paper (peer-reviewed)abstract
- Many countries are looking to public transport to alleviate problems of congestion and pollution and increase sustainability. In order to develop a large modal shift in traveller behaviour, transport providers and planners need to deliver a high quality passenger experience. This paper firstly introduces the EU funded METPEX project, the aim of which is to develop a Pan European tool to measure the quality of the whole journey experience, and secondly discusses the results of stakeholder interviews in the UK, which show where such a tool might fill gaps in existing knowledge of passenger behaviour and mobility requirements.
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