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Optimal Codes for Complex Brains: Constraints and Trade-offs in the Hippocampus and Neocortex
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321283.pdf (Publisher’s version ) (Open Access)Complex animal brains have evolved the ability to represent their environments. However, physical and biological constraints, such as having unreliable synapses or a limited energy budget, impose trade-offs that have shaped the evolution of optimal coding strategies. In this thesis, a range of mathematical modeling techniques are used to explore the rationale behind the coding schemes employed by two brain structures that are critical for sensory representation: the hippocampus and the neocortex. First, the hippocampus is investigated to understand how it compresses sensory inputs into sparse representations to store episodic memories using a limited number of neurons, a process that gives rise to the well-known place cell code. Then, it is shown how noise and intrinsic time constants constrain the oscillation frequencies at which place cells can effectively encode inputs to the hippocampus, restricting them to low frequencies such as the theta band. The focus then shifts to neural populations in the neocortex, showing that noise determines the precise balance between different inhibitory sources required to maintain near-critical dynamics for optimal sensory encoding and decision-making. The thesis concludes by discussing the importance of constraints and trade-offs in advancing our understanding of the brain, as well as their impact on the design of advanced cognitive systems in artificial intelligence.Radboud University, 05 september 2025Promotores : Verschure, P.F.M.J., Tiesinga, P.H.E., Kappen, H.J.xi, 138 p
Pelvic Lymph Node Dissection in Prostate Cancer: Evidence and Implications.
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319819.pdf (Publisher’s version ) (Open Access)The role of extended pelvic lymph-node dissection (ePLND) in prostate cancer has been revisited in light of evidence from studies on staging via prostate-specific membrane antigen positron emission tomography/computed tomography. It is difficult to predict which individuals might benefit from ePLND. Patients should be counselled about this uncertainty and the risks of ePLND-associated morbidity as part of the shared decision-making process.01 juni 202
Uitsluiting in de politiek: Over ervaren representatie bij personen met een migratieachtergrond
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321163.pdf (Publisher’s version ) (Open Access)In dit artikel gaan we in op de achtergronden van ervaren politieke representatie van personen met een migratieachtergrond. Door de bank genomen wordt de Nederlandse politiek, en dan wordt vooral gesproken over de Haagse politiek, gezien als weinig divers en erg wit. Voor Nederlanders met een migratieachtergrond is een overeenkomstige migratieachtergrond met politici belangrijk, omdat deze politici bepaalde, gedeelde ervaringen in de politieke arena kunnen articuleren. Descriptieve vertegenwoordiging is voor veel Nederlanders met een migratieachtergrond daarmee een eerste stap naar ervaren inhoudelijke vertegenwoordiging. In het artikel laten we zien dat descriptieve vertegenwoordiging niet zonder meer leidt tot een sterke ervaren inhoudelijke politieke vertegenwoordiging. Dit wordt door de respondenten in dit onderzoek onder meer toegeschreven aan het politieke systeem, dat weinig ruimte biedt om vraagstukken rondom diversiteit, inclusie en discriminatie voor het voetlicht te brengen. Ervaren uitsluiting is een belangrijke factor voor ervaren politieke representatie. Het gevoel dat groepen en personen uiteindelijk niet meetellen, draagt bij aan ervaren afstand ten opzichte van het politieke systeem. De manier waarop in het politieke en publieke debat wordt gesproken en gehandeld over zaken als migratie, discriminatie en racisme en diversiteit, heeft zijn weerslag op ervaren representatie. Het narratief dat personen met een migratieachtergrond vaak van wezenlijk belang vinden, vindt geen ingang en vertaling in de politiek. English abstract: In this article we discuss perceived political representation of people with a migration background. Generally speaking, Dutch politics and especially national politics, is seen as not very diverse and very white. For Dutch people with a migration background, having a similar migration background with politicians is important because certain experiences are shared that political representatives can articulate in the political arena. For many Dutch people with a migration background, descriptive representation is a first step towards experienced substantive representation. In the article we show that descriptive representation does not automatically lead to strong perceived substantive political representation. The respondents in this study attribute this, among other things, to the political system, which offers little room to highlight issues surrounding diversity, inclusion and discrimination. Perceived exclusion is an important factor for perceived political representation. The feeling that groups and individuals ultimately do not count contributes to perceived distance from the political system. The way in which issues such as migration, discrimination, racism and diversity are discussed and acted upon in the political and public debate has an impact on perceived representation. The narrative that people with a migration background often consider essential is not accepted and translated into politics.12 p
Hypothermia and Adverse Outcomes in Very Preterm Infants: A Systematic Review.
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318969.pdf (Publisher’s version ) (Open Access)CONTEXT: Hypothermia after very preterm birth, typically defined as a temperature less than 36 °C, is variably linked to neonatal mortality and morbidities. OBJECTIVE: To examine the association between admission hypothermia and adverse outcomes in very preterm infants with a gestational age (GA) of less than 32 weeks. DATA SOURCES: CENTRAL, MEDLINE, and Embase from inception to February 18, 2024. STUDY SELECTION: Observational or randomized designs reporting on the association between admission temperature and adverse outcomes in very preterm infants. DATA EXTRACTION: Two reviewers screened abstracts and full texts, extracted the data, and assessed the risk of bias, following Meta-analysis Of Observational Studies in Epidemiology /Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We planned to perform random-effects meta-analyses, subgroup (GA, birthweight [BW], and income), sensitivity analysis (NOS, study type), and meta-regression (GA, BW). Outcomes included mortality and neonatal morbidities: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy (ROP), and sepsis. RESULTS: This review included 32 studies with >300 000 infants. The mean hypothermia rate was 42% (range 14%-88%). Hypothermia was associated with increased mortality (crude odds ratio [cOR] [95% CI] 2.02[1.84;2.21]; adjusted OR 1.55[1.29;1.87]). Subgroup and sensitivity analyses upheld these results. Meta-regression analysis showed an inversed relationship between effect size and BW. Hypothermia was associated with higher risks of BPD (cOR 1.13[1.01;1.27]), IVH (cOR 1.37[1.17;1.61]), ROP (cOR 1.55[1.41;1.69]), and sepsis (cOR 1.32[1.16;1.51]). LIMITATIONS: Only observational studies were included. CONCLUSIONS: Hypothermia is associated with increased mortality and morbidity in very preterm infants. The strength of this association may be influenced by BW, definitions of hypothermia and outcomes, and exclusion criteria. Given the robustness of our results and our sample size, identical cohort studies might not provide different insights
From Divergence to Convergence. A Historical Perspective on PreInsolvency Restructuring in the Netherlands and Belgium
No full textItem does not contain fulltextINSOL Academic Colloquium, 22 mei 2025Invited lectur
Genome wide population genetics and molecular surveillance of insecticide resistance in <i>Anopheles stephensi</i> mosquitoes from Awash Sebat Kilo in Ethiopia
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319617.pdf (Publisher’s version ) (Open Access)12 p
Evaluation of a patient decision aid for opportunistic salpingectomy and salpingectomy as sterilization method to prevent ovarian cancer.
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319659.pdf (Publisher’s version ) (Open Access)INTRODUCTION: A patient decision aid on opportunistic salpingectomy and salpingectomy as a sterilization method has been developed to provide uniform counseling and reduce practice variation. The aim of this study was to evaluate the use of the patient decision aid in daily clinical practice to ensure its effectiveness and usability, as well as its influence on the decision-making process and the decision of opportunistic salpingectomy. MATERIAL AND METHODS: As part of the STOPOVCA-implementation study, we conducted a multicenter observational study in 16 hospitals between July 2020 and February 2024. Patients who were eligible for opportunistic salpingectomy were invited to use the decision aid while they considered whether or not to undergo opportunistic salpingectomy. Digital questionnaires were used to evaluate the decision aid, the decision process, and patients' decisions 6-8 weeks post-surgery. RESULTS: 425 out of 542 patients participated in the questionnaire. A majority of these 425 patients received (N = 357; 84%) and used the decision aid (N = 347; 82%). Two thirds (N = 234; 67%) of those who used the decision aid stated that it increased their knowledge of opportunistic salpingectomy. Patients considered the decision aid a usable aid, allocating a score of 8.1 out of 10 and would recommend it to other patients facing the decision regarding opportunistic salpingectomy. Patients considered the extent to which they were involved in the decision-making process as high, and the decisional conflict low. The majority of patients who used the decision aid opted for opportunistic salpingectomy (N = 326; 95%). Main reasons for choosing opportunistic salpingectomy were the risk-reducing effect of ovarian cancer (N = 311; 90%) and the lack of functionality of the fallopian tubes after childbearing (N = 320; 92%). CONCLUSIONS: The patient decision aid was used by a majority of patients who received it. The decision aid was regarded by patients as user-friendly, and it was recommended to be used in the decision-making process for opportunistic salpingectomy. Patients stated that the decision aid provides reliable information and increases patients' knowledge of opportunistic salpingectomy.01 juni 202
Shareholder Activism and ESG. From Locust to Green Knight? A Perspective from the Netherlands
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320210.pdf (Publisher’s version ) (Open Access)In this article, we will answer the questions (i) what is the role and what are the rights of activist shareholders under Dutch law, (ii) how these rights relate to ESG developments, and (iii) whether the associated changes in shareholder activism will affect the existing negative image of activist shareholders and their limited rights. We will examine all of this against the backdrop of recent developments – both legislative and practical – around ESG and the broad public support for it. In other words: will the pendulum that in recent years has placed the power in the company in the hands of the management board and the supervisory board swing back a bit toward the shareholders? We will discuss these matters from the Dutch perspective and will focus on the rights of shareholders according to Dutch law.
The structure is as follows. In Section 2, we first outline the current playing field. What and who are activist shareholders, what do they want, what strategies do they employ and what trends can be discerned in practice? In Section 3, we provide a brief overview of the legal and non-legal "tools" that activist shareholders use. In Section 4 we discuss some recent developments in the field of ESG legislation and examine whether those developments affect or should affect existing shareholder rights. In Section 5 we discuss some additional "routes of attack" that the ESG-oriented activist shareholder can take. In Section 6, we wrap up with a brief conclusion.15 juni 202528 p
Recurrence prediction using circulating tumor DNA in patients with early-stage non-small cell lung cancer after treatment with curative intent: A retrospective validation study.
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318933.pdf (Publisher’s version ) (Open Access)BACKGROUND: Despite treatment with curative intent, many patients with localized non-small cell lung cancer (NSCLC) develop recurrence. The current challenge is to identify high-risk patients to guide adjuvant treatment. Identification of residual disease by detection of circulating tumor DNA (ctDNA) may allow more accurate clinical decision-making, but its reliability in NSCLC is not established. We aimed to build on previous data to validate a tissue-informed personalized ctDNA assay, to predict recurrence in patients with early-stage disease. METHODS AND FINDINGS: Tumor tissue and plasma was collected from patients with stage 0-III NSCLC enrolled to LEMA (Lung cancer Early Molecular Assessment trial, NCT02894853). Serial plasma was collected before and after definitive treatment, with the latter including key timeframes of interest (1-3 days post-treatment, between 14 and 122 days after treatment end, and ≥14 days after treatment end). Somatic mutations identified by tumor exome sequencing were used to design patient-specific assays, to analyze ctDNA. Results were compared and combined with an independent dataset (LUCID; LUng Cancer CIrculating Tumour Dna study, NCT04153526). In LEMA, 130 patients (57% male; median age 66 years (range 44-82); 69% adenocarcinoma, 22% squamous cell carcinoma (SCC); 3%/49%/19%/29% with stage 0/I/II/III) were treated with curative intent. Tumor tissue originated from surgical resection or diagnostic biopsy in 118 and 12 patients respectively. LUCID included 88 patients (51% male; median age 72 years (range 44-88); 63% adenocarcinoma, 31% SCC; 49%/28%/23% with stage I/II/III). Before treatment, ctDNA was detected in 48% LEMA and 51% LUCID patients. Sensitivity, specificity, positive and negative predictive value of ctDNA detection post-treatment (≥1 positive sample ≥14 days after treatment end) to predict recurrence were 61%, 97%, 92% and 84% for LEMA and 64%, 96%, 90% and 83% for LUCID. In the combined cohort, ctDNA detection after treatment was associated with shorter recurrence-free survival (hazard ratio (HR) 11.4 (95% confidence interval (CI) [7.0,18.7]; p < 0.001)) and overall survival (HR 8.1 (95% CI [4.6,14.2]; p < 0.001)), accounting for guarantee-time bias. Of note, a key limitation of this work was the irregular sample collection schedules, during routine follow-up visits, of both studies. CONCLUSIONS: ctDNA detection predicted recurrence in independent retrospective cohorts with notable reproducibility, including near-identical detection rates and predictive values, confirming its ability to differentiate patients at high- versus low risk of recurrence. Our results support the potential of tissue-informed ctDNA analysis as a decision-support tool for adjuvant therapy in NSCLC.01 april 202
Crossing the spectrum of neurodevelopmental disorder research: the promise of a multidisciplinary approach
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321071.pdf (Publisher’s version ) (Open Access)More than 2000 different syndromic neurodevelopmental disorders are known. These syndromes are individually rare, but collectively common as they occur in 1:300 births. The impact of neurodevelopmental disorders (e.g. intellectual disability) is large. Multidisciplinary research is necessary to improve care for this patient group. This thesis demonstrates that the same DNA aberration can be present in a healthy parent and their child with typical Snijders Blok-Campeau syndrome. Furthermore, Witteveen-Kolk syndrome can now also be diagnosed based on epigenetics (regulation of DNA). For Brunner syndrome we developed recommendations for diagnostics and management, including the advise to avoid certain medications because of the risk for life-threatening complications. Lastly, brain organoids (“mini-brains”) of individuals with KBG syndrome showed aberrant brain development in KBG syndrome. This knowledge will contribute to improve treatment for KBG syndrome in the future.Radboud University, 22 september 2025Promotores : Kleefstra, T., Egger, J.I.M., Kolk, S.M.332 p