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Adiposity programming in early life : Advancing knowledge about potential determinants in healthy infants
Get PDFPerinatal Determinants of Child Brain Development: a Population-Based Neuroimaging Study
Get PDFLittle is known about the effect of maternal health during pregnancy on offspring brain development on a long term. Embedded in a prospective population-based cohort, we investigated perinatal maternal depression and nutrients in relation to child brain developmen
Modeling and solving line planning with integrated mode choice
Get PDFWe present a mixed-integer linear program (MILP) for line planning with integrated mode and route choice. In contrast to existing approaches, the mode and route decisions are modeled according to the passengers' preferences while commercial solvers can be applied to solve the corresponding MILP. The model aims at finding line plans that maximize the profit for the public transport operator while estimating the corresponding passenger demand with choice models. Both components of profit, revenue and cost, are influenced by the line plan. Hence, the resulting line plans are not only profitable for operators but also attractive to passengers. By suitable preprocessing of the passengers' utilities, we are able to apply any choice model for mode choices using linear constraints. We provide and test means to improve the computational performance. In experiments on the Intercity network of the Randstad, a metropolitan area in the Netherlands, we show the benefits of our model compared to a standard line planning model with fixed passenger demand. Furthermore, we demonstrate with the help of our model the possibilities and limitations for operators when reacting to changes in demand in an optimal way. The results suggest that operators should regularly update their line plan in response to changes in travel demand and estimate the passenger demand during optimization
CYP11B1 variants influence skeletal maturation via alternative splicing
No full textWe performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10−12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10−40), exon 4 inclusion (P = 4.29 × 10−34), and decreased exon 3 and 5 splicing (P = 7.85 × 10−43), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.</p
Liminagraphy: Lessons in Life-affirming Research Practices for Collective Liberation
Get PDFIn The Master’s Tools Will Never Dismantle the Master’s House Audre Lorde asks us to take seriously the question “What does it mean when the tools of a racist patriarchy are used to examine the fruits of that same patriarchy?” she goes on to answer “It means that only the most narrow perimeters of change are possible and allowable” (2017 [1979]: 17)*. Using Lorde’s dictum as an anchor, this thesis provides a decolonial feminist critique of the modern/colonial knowledge system whilst simultaneously arguing for a reclaiming of knowledges and research practice. In doing so it highlights the need for radical alternatives in our approaches to knowledge, justice and collective liberation, offering Liminagraphy as one possible pathway.
The research undertaken set out to find the ways in which we can cultivate knowledge that is epistemically non-violent in the context of the racialized, gendered, colonial and neoliberal university. Through conversations with women of colour and those who resist the logics of dominant knowledge production, it was learned that this involves the simultaneous processes of decolonizing the self, dispelling myths around gender and identity, refusing knowledge production as a practice, embracing multiple forms of knowing, and lastly, underscoring the necessity of building coalition across difference for collective liberation. These lessons then provided the fertile ground upon which liminagraphy germinated. Embedded in a decolonial feminist and transformative justice approach, with a relational-ethics at its core, Liminagraphy provides tools and practices which address the ‘how’ of decolonizing, ensuring that erasure, extraction and harm are mitigated in the research process. Thus, Liminagraphy is envisioned as a life-affirming approach to research that offers a pathway to decolonial re-existence and collective liberation through relationality, reciprocity, accountability and coalition.
Whilst this thesis builds upon the many valuable contributions to decolonizing specific disciplines and methodology its particular focus is on the unlearning of the researcher as expert and their reorientation towards life-affirming practices through being/becoming in relation. As such its main contribution is to debates on decolonizing methodology. In addition, it also contributes to discussions on anti-colonial approaches to development studies by radically questioning the inequities that underpin mainstream developmental research practices, thus highlighting disciplinary limitations. Using a radical approach which interrogates the practice of research, at the level of epistemology, ontology, methodology, axiology and the written form, this thesis contributes to generatively conceptualizing knowledge beyond disciplinary and western frameworks. Using poetry, storytelling and podcast as forms of enfleshed theorizing, its innovation lies in its refusal of taken-for-granted research protocols, providing a new approach to research which meaningfully engages with intersectional-positionality, abolitionist practices and what it means to dream-live-feel-think-sense-practice collective liberation
Maternal Early-Pregnancy Glucose Concentrations and Liver Fat Among School-Age Children
No full textBackground and Aims: Gestational diabetes seems to be associated with offspring NAFLD. We hypothesized that maternal glucose concentrations across the full range may have persistent effects on offspring liver fat accumulation. Approach and Results: In a multiethnic, population-based, prospective cohort study among 2,168 women and their offspring, maternal early-pregnancy glucose concentrations were measured at a median of 13.1 weeks’ gestation (95% CI, 9.6-17.2). Liver fat fraction was measured at 10 years by MRI. NAFLD was defined as liver fat fraction ≥5.0%. We performed analyses among all mothers with different ethnic backgrounds and those of European ancestry only. The multiethnic group had a median maternal early-pregnancy glucose concentration of 4.3 mmol/L (interquartile range, 3.9-4.9) and a 2.8% (n = 60) prevalence of NAFLD. The models adjusted for child age and sex only showed that in the multiethnic group, higher maternal early-pregnancy glucose concentrations were associated with higher liver fat accumulation and higher odds of NAFLD, but these associations attenuated into nonsignificance after adjustment for potential confounders. Among mothers of European ancestry only, maternal early-pregnancy glucose concentrations were associated with increased odds of NAFLD (OR, 1.95; 95% CI, 1.32; 2.88, after adjustment for confounders) per 1-mmol/L increase in maternal early-pregnancy glucose concentration. These associations were not explained by maternal prepregnancy and childhood body mass index, visceral fat, and metabolic markers. Conclusions: In this study, maternal early-pregnancy glucose concentrations were only among mothers of European ancestry associated with offspring NAFLD. The associations of higher maternal early-pregnancy glucose concentrations with offspring NAFLD may differ between ethnic groups.</p
Evidence-based decision making on drug reimbursement in melanoma : Using real-world evidence to complement evidence from randomized controlled trials
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Association between shockable rhythms and long-term outcome after pediatric out-of-hospital cardiac arrest in Rotterdam, the Netherlands
No full textIntroduction: Shockable rhythm following pediatric out-of-hospital cardiac arrest (pOHCA) is consistently associated with hospital and short-term survival. Little is known about the relationship between shockable rhythm and long-term outcomes (>1 year) after pOHCA. The aim was to investigate the association between first documented rhythm and long-term outcomes in a pOHCA cohort over 18 years. Methods: All children aged 1 day–18 years who experienced non-traumatic pOHCA between 2002–2019 and were subsequently admitted to the emergency department (ED) or pediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital were included. Data was abstracted retrospectively from patient files, (ground) ambulance and Helicopter Emergency Medical Service (HEMS) records, and follow-up clinics. Long-term outcome was determined using a Pediatric Cerebral Performance Category (PCPC) score at the longest available follow-up interval through august 2020. The primary outcome measure was survival with favorable neurologic outcome, defined as PCPC 1–2 or no difference between pre- and post-arrest PCPC. The association between first documented rhythm and the primary outcome was calculated in a multivariable regression model. Results: 369 children were admitted, nine children were lost to follow-up. Median age at arrest was age 3.4 (IQR 0.8–9.9) years, 63% were male and 14% had a shockable rhythm (66% non-shockable, 20% unknown or return of spontaneous circulation (ROSC) before emergency medical service (EMS) arrival). In adolescents (aged 12–18 years), 39% had shockable rhythm. 142 (39%) of children survived to hospital discharge. On median follow-up interval of 25 months (IQR 5.1–49.6), 115/142 (81%) of hospital survivors had favorable neurologic outcome. In multivariable analysis, shockable rhythm was associated with survival with favorable long-term neurologic outcome (OR 8.9 [95%CI 3.1–25.9]). Conclusion: In children with pOHCA admitted to ED or PICU shockable rhythm had significantly higher odds of survival with long-term favorable neurologic outcome compared to non-shockable rhythm. Survival to hospital discharge after pOHCA was 39% over the 18-year study period. Of survivors to discharge, 81% had favorable long-term (median 25 months, IQR 5.1–49.6) neurologic outcome. Efforts for improving outcome of pOHCA should focus on early recognition and treatment of shockable pOHCA at scene.</p