Decision making in flood situations for boezem systems: GDH boezem

The Automated Flood Scenario (Geautomatiseerd Draaiboek Hoogwater (GDH) is an automated substitution for current paper based flood scenario’s. The software is originally developed for river systems and support decision makers in taking operational decisions in extreme situations.\ud - It improves control in flood and calamity situations.\ud - It structures actions and information, showing only the relevant information.\ud - It operates on input-parameters (e.g. waterlevel).\ud The GDH concept has been made applicable for boezem systems (Bijlsma, 2005, Bijlsma et al. 2005). The overall question to the research was which adaptations are required to make GDH river suitable for use in boezem systems. Special attention was focused on the question: What information does the boezem manager need as a minimum to take good decisions

A methodology to determine the contribution of stakeholders to the robustness of environmental policy decisions

A methodology is developed in this paper to test the effectiveness of successful stakeholder participation in creating substantively more robust policy, and to identify the factors responsible for that. The comparison is made to a more traditional management of government policy, in which experts in administrative agencies perform the policy analyses. The methodology compares the substantive robustness of the preferred alternative developed in a stakeholder participation process to the robustness of the preferred alternative developed for the same case in an expert-based process. It comprises a case study design that enables realistic performance of both processes, ensures their comparability and guards their quality. The developed methodology appears promising and is currently being applied. A systematic investigation of the relation between stakeholder contribution and the robustness of policy analyses helps formulating arguments for stakeholder involvement. Furthermore it can improve the effectiveness of a participation activity

Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity

Objectives Immunoglobulin (Ig) free light chains (FLCs) are short-lived B cell products that contribute to inflammation in several experimental disease models. In this study, FLC concentrations in inflamed joints of patients with rheumatoid arthritis (RA) as compared to patients with osteoarthritis were investigated. In addition, the relationship of FLCs and disease activity upon B cell depletion (rituximab) in patients with RA was studied. Methods Synovial fluid (SF) and tissue from patients with RA were analysed for local presence of FLCs using ELISA and immunohistochemistry. In addition, FLC concentrations were measured (at baseline, 3 and 6 months after treatment) in 50 patients with RA with active disease who were treated with rituximab. Changes in FLCs were correlated to changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM-rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA) concentrations. Results FLCs were detected in synovial tissue from patients with RA, and high FLC concentrations were found in SF from inflamed joints, which positively correlate with serum FLC concentrations. Serum FLC concentrations significantly correlated with disease activity score using 28 joint counts, erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC correlated with clinical improvement after rituximab treatment. Moreover, effect of treatment on FLC concentrations discriminated clinical responders from non-responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient groups. Conclusions FLCs are abundantly present in inflamed joints and FLC levels correlate with disease activity. The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of R

Trust and control interrelations: New perspectives on the trust control nexus

This article is the post-print version of the published article that may be accessed at the link below. Copyright @ 2007 Sage Publications.This article introduces the special issue on New Perspectives on the Trust-Control Nexus in Organizational Relations. Trust and control are interlinked processes commonly seen as key to reach effectiveness in inter- and intraorganizational relations. The relation between trust and control is, however, a complex one, and research into this relation has given rise to various and contradictory interpretations of how trust and control relate. A well-known discussion is directed at whether trust and control are better conceived as substitutes, or as complementary mechanisms of governance. The articles in this special issue bring the discussion on the relationship between both concepts a step further by identifying common factors, distinctive mechanisms, and key implications relevant for theory building and empirical research. By studying trust and control through different perspectives and at different levels of analysis, the articles provide new theoretical insights and empirical evidence on the foundations of the trust-control interrelations

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p

Comparison of outcome and characteristics between 6343 COVID-19 patients and 2256 other community-acquired viral pneumonia patients admitted to Dutch ICUs

Purpose: Describe the differences in characteristics and outcomes between COVID-19 and other viral pneumonia patients admitted to Dutch ICUs. Materials and methods: Data from the National-Intensive-Care-Evaluation-registry of COVID-19 patients admitted between February 15th and January 1th 2021 and other viral pneumonia patients admitted between January 1st 2017 and January 1st 2020 were used. Patients' characteristics, the unadjusted, and adjusted in-hospital mortality were compared. Results: 6343 COVID-19 and 2256 other viral pneumonia patients from 79 ICUs were included. The COVID-19 patients included more male (71.3 vs 49.8%), had a higher Body-Mass-Index (28.1 vs 25.5), less comorbidities (42.2 vs 72.7%), and a prolonged hospital length of stay (19 vs 9 days). The COVID-19 patients had a significantly higher crude in-hospital mortality rate (Odds ratio (OR) = 1.80), after adjustment for patient characteristics and ICU occupancy rate the OR was respectively 3.62 and 3.58. Conclusion: Higher mortality among COVID-19 patients could not be explained by patient characteristics and higher ICU occupancy rates, indicating that COVID-19 is more severe compared to other viral pneumonia. Our findings confirm earlier warnings of a high need of ICU capacity and high mortality rates among relatively healthy COVID-19 patients as this may lead to a higher mental workload for the staff. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Unsolicited genetic findings in clinical oncology : Cancer patients' needs and preferences in the era of DNA sequencing

The research described in this thesis focuses on cancer patients’ intentions, needs and preferences with regard to receiving unsolicited genetic information obtained by tumor DNA analysis. We combine qualitative research and quantitative research methods with a normative ethical reflection on the introduction of DNA sequencing into daily practice in clinical oncology. In precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in cancer patients. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand cancer patients’ preferences concerning UFs derived from sequencing. Cancer patients may be particularly vulnerable (physical and emotional) at the moment they have to make decisions concerning NGS and possible unsolicited findings. Understanding what a cancer patient could experience during the process of disclosing unsolicited findings from NGS will help oncologists in daily practice to accompany patients in making informed decisions In one of our qualitative studies, four interrelated themes were recognized when cancer patients were asked about their preferences, intentions, and needs concerning the return of unsolicited findings generated during a NGS procedure: cancer patients’ need to control their lives (theme 1), associated family dynamics (theme 2), and dealing with both the cognitive complexity (theme 3) and emotional complexity (theme 4) of receiving the findings. These insights with regard to the four themes contribute to a better understanding of what cancer patients consider important, and what motivates and influences them when they make decisions on the disclosure of unsolicited findings. This thesis also shows that education and counseling are vital to enable cancer patients to make informed decisions. Even for highly educated people, this topic is rather difficult to understand. Thus, to make an informed, autonomous decision with regard to the return of unsolicited findings, understandable, personalized and accessible information (written or digital) and educational material must be available to empower cancer patients and their family members. Our quantitative study showed that the vast majority of cancer patients desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable findings. Importantly, the interest in learning about four different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance) is equally high among curative and advanced-stage patients. However, there is also a substantial group of patients who do not want to be informed. Presenting categories of genetic test results was found to be a useful tool in enabling cancer patients to make a well-informed decision about receiving unsolicited findings from NGS A binning approach to UFs allows patients to accept actionable findings and at the same time to refuse non-actionable or uncertain findings. Binning helps a considerable minority of patients who do not wish to know everything. Especially women would benefit from differentiating between categories of UFs along these lines

Unsolicited genetic findings in clinical oncology : Cancer patients' needs and preferences in the era of DNA sequencing

The research described in this thesis focuses on cancer patients’ intentions, needs and preferences with regard to receiving unsolicited genetic information obtained by tumor DNA analysis. We combine qualitative research and quantitative research methods with a normative ethical reflection on the introduction of DNA sequencing into daily practice in clinical oncology. In precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in cancer patients. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand cancer patients’ preferences concerning UFs derived from sequencing. Cancer patients may be particularly vulnerable (physical and emotional) at the moment they have to make decisions concerning NGS and possible unsolicited findings. Understanding what a cancer patient could experience during the process of disclosing unsolicited findings from NGS will help oncologists in daily practice to accompany patients in making informed decisions In one of our qualitative studies, four interrelated themes were recognized when cancer patients were asked about their preferences, intentions, and needs concerning the return of unsolicited findings generated during a NGS procedure: cancer patients’ need to control their lives (theme 1), associated family dynamics (theme 2), and dealing with both the cognitive complexity (theme 3) and emotional complexity (theme 4) of receiving the findings. These insights with regard to the four themes contribute to a better understanding of what cancer patients consider important, and what motivates and influences them when they make decisions on the disclosure of unsolicited findings. This thesis also shows that education and counseling are vital to enable cancer patients to make informed decisions. Even for highly educated people, this topic is rather difficult to understand. Thus, to make an informed, autonomous decision with regard to the return of unsolicited findings, understandable, personalized and accessible information (written or digital) and educational material must be available to empower cancer patients and their family members. Our quantitative study showed that the vast majority of cancer patients desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable findings. Importantly, the interest in learning about four different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance) is equally high among curative and advanced-stage patients. However, there is also a substantial group of patients who do not want to be informed. Presenting categories of genetic test results was found to be a useful tool in enabling cancer patients to make a well-informed decision about receiving unsolicited findings from NGS A binning approach to UFs allows patients to accept actionable findings and at the same time to refuse non-actionable or uncertain findings. Binning helps a considerable minority of patients who do not wish to know everything. Especially women would benefit from differentiating between categories of UFs along these lines