Radboud Institute for Molecular Life Sciences

Hospital inflation reflects changes in prices of labour, materials, energy, and capital. Depending on actual cost structures and contracts, individual hospitals may experience different price pressures on their budgets. If hospitals are compensated uniformly for inflation, high inflation can induce significant disparities in profitability. To analyse the differential impact of inflation on hospitals in the Netherlands. We test the hypothesis that differences in hospital-specific inflationary pressures were reflected in hospital compensation for inflation. Under this hypothesis, hospital-specific inflation rates correlate with overall budget growth. Using hospital financial data, we calculated hospital-specific inflation rates by combining cost categories with corresponding inflation rates for 2006-2023. Using linear regression analysis, we tested whether hospital-specific inflation rates correlated with reimbursements between 2006-2021. Next, we simulated differential impact for hospitals of high inflation in 2022-2023. Five stakeholder interviews validated results and explored inflation compensation mechanisms in practice. We found that inflation causes significant variance in individual hospital inflation rates, magnified after 2021 by high overall inflation. Linear regression showed no significant correlation between variation in observed hospital reimbursement and variation in hospital specific inflation rates, indicating that historically no differential inflation adjustments occurred. Interviewees stated that insurers do not explicitly take into account differential inflation impact between hospitals, and that hospitals were only partly compensated for general inflation. Dutch hospitals are not fully compensated for cost inflation and health insurers do not differentiate for differences in hospital-specific inflation rates. High inflation rates could thus induce significant disparities in hospital profitability.

Follow-up of radiologically suspicious lung nodules from screening programs remains complex and unstandardized. This study analyses distribution and characteristics of solid and part-solid non-calcified nodules ≥100mm3 and non-solid nodules ≥8mm detected at baseline in the UK Lung cancer Screening (UKLS) trial, with insights into their relationship to screen-detected lung cancers. UKLS participants with baseline indeterminate and positive lung nodules were included. Nodule location was categorized by lobe and by attachment: intraparenchymal, juxta pleural or pleural-based. Solid and part-solid were classified based on semi-automated volume: 100-300mm3 and ≥300mm3, and non-solid nodules based on diameter ≥8mm. This measurement approach aligns with UKLS protocol and the British Thoracic Society (BTS) guideline. Their relationship to screen-detected lung cancer was based on histological outcomes after a 2-year follow-up period. 279 UKLS participants with 373 solid or part-solid lung nodules ≥100mm3 and 57 participants with 62 nonsolid nodules ≥8mm were included. Among solid and part-solid nodules, 233 were 100-300mm3, with 39.5% in upper lobes and 72.5% intraparenchymal; 140 nodules were ≥300mm3, with 51.4% in upper lobes and 53.6% intraparenchymal. Nodules ≥300mm3 group were more likely to be in the upper lobes (OR 1.97 [95% CI 1.12-3.48]). Within 2years, 34 solid or part-solid nodules were diagnosed as lung cancer, yielding a 2-year cancer probability of 9.1% (95% CI 6.6-12.5). The 2-year lung cancer probability was higher in nodules ≥300mm3 (RR 18.1, 95% CI 5.6-58.4; p<0.001) and in upper lobe nodules (RR 2.7, 95% CI 1.3-5.5; p=0.009). Solid and part-solid nodules with volume ≥300mm3 were more often found in the upper lobes and were associated with a higher probability of lung cancer within a two-year follow-up period.

People with HIV (PWH) using antiretroviral therapy are at increased risk to develop cardiovascular diseases (CVD). We hypothesized that residual viremia (RV; unquantifiable low, but detectable viral load) increases CVD risk. We enrolled 1895 virally suppressed PWH and compared CVD incidence in participants with and without RV. Extensive multi-omics characterization was performed. Incident CVD was registered after 2-year follow-up and adjusted odds ratios (aOR) calculated accounting for classical CVD risk factors. The numbers of expected and actual CVD events were compared using CVD risk scores. RV, detected in one-third of participants, strongly increased the risk of developing a first cardiovascular event (3.1% vs 1.2%, aOR 2.8,p=0.004). Participants with RV experienced twice the number of events predicted by the SCORE2 riskmodel. The association between RV and CVD was not driven by inflammation, immune activation, gut barrier dysfunction, or lipometabolic perturbations. Residual viremia independently associated with CVD development, highlighting the need for tailored prevention and examination of novel intervention strategies.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory condition with potentially major implications for the lives of those it affects. In the past decade, the identification of clinically relevant patient characteristics - 'treatable traits' (TTs) - has received wide support as an important means of improving care. These traits can be categorised into three domains: pulmonary, extra-pulmonary and behavioural. Many patients with COPD have multiple TTs in various combinations. For this reason, the successful application of a TT approach requires a thorough assessment of the patient's health status to elicit relevant TTs. Combined with the patient's preferences and priorities, these traits enable the formulation of an individualised treatment plan. Execution of this plan often requires interprofessional collaboration among relevant healthcare providers and case management. Although international consensus appears to exist concerning the benefits of providing care according to the TT concept, widespread implementation in care is slow. Although pulmonary rehabilitation programmes have adopted the concept by definition, it has yet to be applied widely in practice, especially in primary and secondary care. We have used the TT model to develop a comprehensive model of care that contains all three elements (assessment, treatment plan and execution) and that provides insight into considerations and decisions regarding where such care should be provided. This paper describes the process, results and challenges of our attempts to design and implement this integrated care concept.

Background Despite growing scientific evidence and health guidelines, the global health paradox persists, with rising lifestyle-related diseases and escalating healthcare costs exposing the inadequacy of current efforts. Objective Three multidisciplinary congresses were held to generate evidence-based conclusions aimed at addressing the global health paradox. Methods A total of 58 experts from 62 entities participated in the international research and knowledge-exchange panels. Experts reviewed the latest findings to develop practical strategies and identify key research and policy priorities, focusing on the Healthy Eating &amp;amp; Active Living (HEAL) approach. Results, conclusion, and relevance The expert consortium endorsed a 33 evidence-based consensual-statement policy roadmap for addressing global health challenges, emphasizing that the HEAL approach can significantly contribute to the “Prevention First” appeal and broad ethical, social, ecological, and economic advantages, and ultimately supporting policy change.

Wetlands are recognised as one of the most important ecosystems in terms of their unique biodiversity. Yet since 1900, the world has lost more than 50% of its wetland area (Davidson, 2014; Dugan, 2005; Winkler &amp; DeWitt, 1985). Groundwater dependent wetlands (GDWs) provide critical ecological functions but face increasing pressure from climate variability and groundwater abstraction, while their global extent and dynamics remain poorly quantified. Here we present the first spatially and temporally explicit global assessment of GDW extent using a high resolution, physically based groundwater modelling framework.We developed a dynamic GDW mapping framework based on GLOBGM global groundwater model (Verkaik et al. (2022), a 30 arc second, two-layer MODFLOW model, coupled offline with PCR-GLOBWB (Sutanudjaja et al., 2018). We include improved recharge estimates through bias correction and enhanced groundwater-surface water coupling via dynamically updated drainage elevation using saturated area fraction to better represent shallow groundwater processes.Following ISIMIP3a and ISIMIP3b protocols, we simulated monthly groundwater conditions from 1960 to 2014 and projected changes up to 2050 under SSP1-2.6, SSP3-7.0 and SSP5-8.5 using five CMIP6 global climate models per scenario (Lange &amp; Büchner, 2021). Evaluation of groundwater heads against more than 15000 wells from the IGRAC dataset (IGRAC, 2024) show strongest performance for shallow water tables (average depth less than 5m) with about 67 % of wells with Kling Gupta Efficiency KGE ≥ −0.41.Following earlier work (Otoo et al., 2025), we identified GDWs as areas with a saturated area fraction greater than 0.5 and water table depth less than or equal to 5 m, capturing both core groundwater fed wetlands and peripheral drought adapted systems while accounting for sub-grid variability. We exclude areas where groundwater results remain unreliable due to spin up issues, karst, permafrost and mountain areas (in total, only about 19 % of global areas). This approach shows strong spatial agreement with independent datasets, achieving a global hit rate of 76 % against the Global Lakes and Wetlands Database 2 (GLWD 2) (Lehner et al, 2025), and exceeding 80 % against the Australian Atlas (Doody et al., 2017).We also account for land conversion when simulating area changes by excluding potential GDWs that coincide with agricultural areas in PCR-GLOBWB (rainfed and irrigated agriculture and pasture) for both past and future periods. For the historical period, we attributed groundwater level trends to climate-driven recharge changes, human-driven groundwater abstraction or a combination of both and quantified GDW area changes aggregated by WWF biome realm units (Olson et al., 2001). Preliminary results show strong reductions of past and future wetlands in Afrotropical, Indo-Malayan and Neotropical regions with distinct areas where either groundwater level decline or land use change are the dominant drivers. This framework addresses a major gap in global wetland assessments and provides a physically groundwater basis for evaluating past and future GDW dynamics in support of conservation planning, climate impact assessment and policy development aligned with Ramsar Convention, the Sustainable Development Goals and global biodiversity targets.

Dental education prepares students for independent practice, handling both predictable and unpredictable challenges. This necessitates a prospective approach to supervision and assessment, as such an approach not only evaluates current performance but also anticipates future behaviour. Entrustable Professional Activities (EPAs) offer a structured framework to develop and assess trust in students, supporting this prospective perspective. Although EPAs were originally designed for postgraduate training, they are increasingly used in undergraduate programs. While existing literature outlines factors influencing entrustment decisions, little is known about how these factors operate within dental education. This study explores how entrustment is enacted in dentistry and examines its potential link to adaptive expertise, which further promotes a prospective approach to supervision and assessment. A focused ethnography was conducted to gain in-depth insight into entrustment decision-making, based on observations and interviews during clinical practice and academic clinical reasoning sessions, and interviews reflecting on these observations. Data collection was followed by template analysis, using a theoretical background based on literature on ad hoc and summative entrustment decisions, retrospective and prospective entrustment, the A RICH framework, and conceptualisations and operationalisations of adaptive expertise. Throughout every phase of the study, an iterative process took place involving the entire research team. Data collection involved 56 h of observations and 9 interviews with dental supervisors. Ad hoc entrustment decisions are made daily by supervisors. All factors known from the literature to influence entrustment decisions were observed, including the A RICH features of students and students’ adaptive expertise and adaptive performance. The patient as an actor emerged as an additional factor influencing entrustment. This study highlights the increasing applicability of EPAs in dental education. It confirms the factors influencing entrustment decisions, adds the patient as a sixth factor, and supports the relevance of the A RICH framework. The findings emphasize a paradigm shift toward trust-based dialogue. However, conversations about entrustment rarely address trainee qualities beyond technical skills explicitly. To enable prospective assessment, curriculum design is crucial: a longitudinal EPA-based curriculum provides essential conditions for supervisors’ entrustment decisions. Further research into key curriculum factors is important to facilitate EPA-based curricula in dental education.

Usher syndrome type 2A (USH2a), the most common form of hereditary deaf-blindness, is frequently accompanied by fatigue and poor sleep quality. As these sleep problems occur independently of visual decline, it is hypothesized that the USH2A-encoded protein usherin regulates sleep and circadian rhythmicity via an extra-retinal mechanism. Ush2a knockout zebrafish models were utilized to investigate this hypothesis. Immunohistochemical analysis demonstrated usherin localisation in pineal gland photoreceptor cells in wild-type larvae, alongside the USH2 complex proteins Adgrv1 and Whrna. Cross-species transcriptomic and proteomic analyses confirmed USH2A expression in all mammalian pineal gland tissues studied. Circadian clock gene expression was measured over 24 h and showed preserved oscillatory patterns in wild-type and mutant zebrafish. Ex vivo superfusion of pineal glands revealed sustained circadian melatonin release with comparable phase and period to controls, although potential differences in absolute melatonin levels could not be excluded. Despite intact clock gene expression and melatonin release in ush2a mutants, behavioural classification over 24-h recordings revealed altered sleep-wake behaviour: ush2a mutants displayed elevated daytime sleep and significantly prolonged and more variable sleep latency. The dissociation between intact molecular rhythms and abnormal sleep behaviour likely implicates that usherin plays a role in sleep-wake regulation independent of the circadian pacemaker and melatonin synthesis. These findings suggest a novel role of usherin in the pineal gland and establish a mechanistic link between usherin dysfunction and sleep disturbances, providing a biological basis for the fatigue and sleep problems reported in USH2a patients.

Controlling magnetic textures at ever smaller length scales and timescales is of fundamental and technological interest. External stimuli capable of acting at the nanoscale pose a challenge, motivating alternative approaches that exploit the intrinsic inhomogeneity of magnetic textures. Here we use a Pt/Co/Pt ferromagnetic thin film to investigate magnetization reversal with circularly polarized picosecond laser pulses. Magnetic force microscopy reveals stochastic nucleation of complex nanotextured domains from an initial monodomain state. Subsequent illumination of these domains with laser pulses induces deterministic and homogeneous magnetization switching. We find that the domain growth depends on the complexity of the texture, revealing a helicity- and texture-dependent mechanism that contrasts with temperature-gradient-driven domain expansion. We complement our observations with a stochastic model in which domain nucleation is governed by light helicity and the local magnetic environment. These results provide an insight into the mechanism of multipulse helicity-dependent all-optical switching.