The moral limits of medical research with children

In mijn proefschrift richt ik mij op het probleem dat medisch-ethische toetsingcommissies onder de huidige Wet Medisch-wetenschappelijk Onderzoek met mensen soms onderzoeksvoorstellen moeten afkeuren die de zorg voor toekomstige zieke kinderen zouden kunnen verbeteren. In deze wet staat namelijk dat de risico__s en belasting van studies die de deelnemende kinderen niet direct ten goede kunnen komen, nooit meer dan __minimaal__ mogen zijn. Uitgangspunt van mijn onderzoek was mijn overtuiging dat bij verruiming van de wet, de bescherming van de proefpersonen wel gewaarborgd moet blijven. Want de eis van minimale risico__s en belasting mag dan problematisch zijn, maar met de onderliggende ethische redenering is niets mis: kinderen zouden in principe niet puur voor onderzoeksdoeleinden aan hoge risico__s en belasting moeten worden blootgesteld. Dankzij mijn multidisciplinaire begeleidingsgroep heb ik het onderwerp van verschillende kanten kunnen bekijken, en bevat het proefschrift niet alleen ethisch-theoretische artikelen, maar ook een analyse van de beslissingen van de centrale toetsingscommissie, een overzicht van de Europese regelgeving, en de verslagen van twee studies naar de wijze waarop kinderen verschillende onderzoeksprocedures ervaren. De conclusie is dat in geval van een __verfijning__ van de huidige wet, met als uitgangspunt een __bescherming op maat__, meer onderzoek mogelijk zou worden, en de bescherming van de proefpersonen eerder zou verbeteren dan verslechteren.ZonMwUBL - phd migration 201

Communicating with Muslim parents: "the four principles" are not as culturally neutral as suggested

The “four principles approach” has been popularly accepted as a set of universal guidelines for biomedical ethics. Based on four allegedly trans-cultural principles (respect for autonomy, nonmaleficence, beneficence and justice), it is supposed to fulfil the need of a ‘culturally neutral approach to thinking about ethical issues in health care’. On the basis of a case-history, this paper challenges the appropriateness of communicating in terms of these four principles with patients with a different background. The case describes the situation in which Muslim parents bring forward that their religion keeps them from consenting to end-of-life decisions by non-religious paediatricians. In a literature analysis, the different meanings and roles of the relevant principles in non-religious and Islamic ethics are compared. In non-religious ethics, the principle of nonmaleficence may be used to justify withholding or withdrawing futile or damaging treatments, whereas Islamic ethics applies this principle to forbid all actions that may harm life. And while the non-religious version of the principle of respect for autonomy emphasises the need for informed consent, the Islamic version focuses on “respect for the patient”. We conclude that the parties involved in the described disagreement may feel committed to seemingly similar, but actually quite different principles. In such cases, communication in terms of these principles may create a conflict within an apparently common conceptual framework. The four principles approach may be very helpful in analysing ethical dilemmas, but when communicating with patients with different backgrounds, an alternative approach is needed that pays genuine attention to the different backgrounds

Gevoelsrendement van natuurontwikkeling langs de rivieren

Met behulp van schriftelijke enquêtes is het effect gemeten van natuurontwikkeling in de uiterwaarden op de beleving of de gevoelswaarde van omwonenden, recreanten en overige Nederlanders. Het gevoelsrendement is gemeten aan de hand van de meningen over de visuele aantrekkelijkheid van de uiterwaarden, het gevoel van verbondenheid, de bestaanswaarde van de natuur en de veiligheidsbeleving. Het gevoelsrendement van de ingrepen blijkt grotendeels positief. Uiterwaarden met riviernatuur worden vooral veel aantrekkelijker gevonden dan uiterwaarden met productiegrasland. Aan de andere kant neemt de binding van omwonenden met het gebied af. De beleving van de uiterwaarden blijkt vooral afhankelijk van de specifieke inrichting, en minder van het formele landschapstype. Door de beleefbaarheid vanaf het begin te betrekken in het beslissings- en ontwerptraject en deze op te nemen als criteria voor de maatregelen en het ontwerp kan weerstand onder de bevolking geminimaliseerd worden

Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort

BACKGROUND: C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G. METHODS: Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood. RESULTS: DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m(2) at last follow-up. CONCLUSIONS: We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05221-6

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Manicured, romantic or wild? The relationship between need for structure and garden styles

The present research examined individual differences in preferences for three basic garden styles: manicured, romantic, and wild. Building on theoretical insights from landscape preference research, it was hypothesized that preferences for garden styles are guided by psychological needs. This hypothesis was empirically tested in two studies that used Personal Need for Structure (PNS; Neuberg and Newsom, 1993) as a predictor of preferences for allotment gardens in the Netherlands. In Study 1, 150 respondents rated the beauty of 30 photos of manicured, romantic, and wild allotment gardens. Results showed that respondents with a high PNS, as compared to respondents with a low PNS, rated wild gardens as less beautiful, and manicured gardens as more beautiful. Study 2 investigated the relationship between the PNS of allotment gardeners and the actual appearance of their gardens. One hundred and twenty-three owners of allotment gardens filled out the PNS scale and classified their garden as manicured, romantic, or wild. Gardeners with a high PNS, as compared to gardeners with a low PNS, more often owned a manicured or romantic garden, and less often owned a wild garden. In both studies, preference for garden types was also related to demographic characteristics, including gender, education level, and age. The theoretical and practical implications of these findings are discussed. (C) 2010 Elsevier GmbH. All rights reserved