Groeven en graven : nieuw leven voor voormalige zandgroeven in Zuid-Limburg

De milieugroep Regionaal Stort Westelijke Mijnstreek vroeg zich af of de zandgroeves bij Spaubeek en Schinnen niet op een betere en snellere manier ingericht konden worden dan in de planvorming tot nu toe gebeurde. Om deze vraag te beantwoorden is een overzicht gemaakt van de regionale behoeften en gekeken of met een aantal ontwerpen aan die behoeften tegemoet gekomen kan worden. Het blijkt dat een op natuur en licht recreatief medegebruik gerichte inrichting het meest aansluit bij de wensen van bewoners en bestuurder

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and >55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with >15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and >55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with >15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients

Een groen spoor door Amersfoort : multifunctioneel landgebruik geeft meerwaarde voor alle partijen

Vereniging Duurzaam Soesterkwartier heeft de afgelopen paar jaar onderzoek laten uitvoeren naar de haalbaarheid van het concept "Groene Spoor". De spoorzone van Amersfoort biedt namelijk een unieke mogelijkheid voor een groene recreatieve verbinding tussen binnenstad en buitengebied, voor meer groen en natuur in de stad, meer ruimte voor natuurspelen, ontmoeting, sport en bewegen. Juist hier liggen kansen doordat het gebied nog volop in ontwikkeling is

Chiral molecule adsorption on helical polymers

We present a lattice model for helicity induction on an optically inactive polymer due to the adsorption of exogenous chiral amine molecules. The system is mapped onto a one-dimensional Ising model characterized by an on-site polymer helicity variable and an amine occupancy one. The equilibrium properties are analyzed at the limit of strong coupling between helicity induction and amine adsorption and that of non-interacting adsorbant molecules. We discuss our results in view of recent experimental results

A metabolomic study on the responses of daphnia magna exposed to silver nitrate and coated silver nanoparticles

Conservation Biolog

More frequent, more costly? Health economic modelling aspects of monitoring glaucoma patients in England

BACKGROUND: Chronic open angle glaucoma (COAG) is an age-related eye disease causing irreversible loss of visual field (VF). Health service delivery for COAG is challenging given the large number of diagnosed patients requiring lifelong periodic monitoring by hospital eye services. Yet frequent examination better determines disease worsening and speed of VF loss under treatment. We examine the cost-effectiveness of increasing frequency of VF examinations during follow-up using a health economic model. METHODS: Two different VF monitoring schemes defined as current practice (annual VF testing) and proposed practice (three VF tests per year in the first 2 years after diagnosis) were examined. A purpose written health economic Markov model is used to test the hypothesis that cost effectiveness improves by implementing proposed practice on groups of patients stratified by age and severity of COAG. Further, a new component of the model, estimating costs of visual impairment, was added. Results were derived from a simulated cohort of 10000 patients with quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) used as main outcome measures. RESULTS: An ICER of £21,392 per QALY was derived for proposed practice improving to a value of £11,382 once savings for prevented visual impairment was added to the model. Proposed practice was more cost-effective in younger patients. Proposed practice for patients with advanced disease at diagnosis generated ICERs > £60,000 per QALY; these cases would likely be on the most intensive treatment pathway making clinical information on speed of VF loss redundant. Sensitivity analysis indicated results to be robust in relation to hypothetical willingness to pay threshold identified by national guidelines, although greatest uncertainty was allied to estimates of implementation and visual impairment costs. CONCLUSION: Increasing VF monitoring at the earliest stages of follow-up for COAG appears to be cost-effective depending on reasonable assumptions about implementation costs. Our health economic model highlights benefits of stratifying patients to more or less monitoring based on age and stage of disease at diagnosis; a prospective study is needed to prove these findings. Further, this works highlights gaps in knowledge about long term costs of visual impairment

GAA Deficiency in Pompe Disease Is Alleviated by Exon Inclusion in iPSC-Derived Skeletal Muscle Cells

Pompe disease is a metabolic myopathy caused by deficiency of the acid α-glucosidase (GAA) enzyme and results in progressive wasting of skeletal muscle cells. The c.-32-13T>G (IVS1) GAA variant promotes exon 2 skipping during pre-mRNA splicing and is the most common variant for the childhood/adult disease form. We previously identified antisense oligonucleotides (AONs) that promoted GAA exon 2 inclusion in patient-derived fibroblasts. It was unknown how these AONs would affect GAA splicing in skeletal muscle cells. To test this, we expanded induced pluripotent stem cell (iPSC)-derived myogenic progenitors and differentiated these to multinucleated myotubes. AONs restored splicing in myotubes to a similar extent as in fibroblasts, suggesting that they act by modulating the action of shared splicing regulators. AONs targeted the putative polypyrimidine tract of a cryptic splice acceptor site that was part of a pseudo exon in GAA intron 1. Blocking of the cryptic splice donor of the pseudo exon with AONs likewise promoted GAA exon 2 inclusion. The simultaneous blocking of the cryptic acceptor and cryptic donor sites restored the majority of canonical splicing and alleviated GAA enzyme deficiency. These results highlight the relevance of cryptic splicing in human disease and its potential as therapeutic target for splicing modulation using AONs

Selection tools and student diversity in health professions education:a multi-site study

Student diversity in health professions education (HPE) can be affected by selection procedures. Little is known about how different selection tools impact student diversity across programs using different combinations of traditional and broadened selection criteria. The present multi-site study examined the chances in selection of subgroups of applicants to HPE undergraduate programs with distinctive selection procedures, and their performance on corresponding selection tools. Probability of selection of subgroups (based on gender, migration background, prior education, parental education) of applicants (N = 1935) to five selection procedures of corresponding Dutch HPE undergraduate programs was estimated using multilevel logistic regression. Multilevel linear regression was used to analyze performance on four tools: prior-education grade point average (pe-GPA), biomedical knowledge test, curriculum-sampling test, and curriculum vitae (CV). First-generation Western immigrants and applicants with a foreign education background were significantly less likely to be selected than applicants without a migration background and with pre-university education. These effects did not vary across programs. More variability in effects was found between different selection tools. Compared to women, men performed significantly poorer on CVs, while they had higher scores on biomedical knowledge tests. Applicants with a non-Western migration background scored lower on curriculum-sampling tests. First-generation Western immigrants had lower CV-scores. First-generation university applicants had significantly lower pe-GPAs. There was a variety in effects for applicants with different alternative forms of prior education. For curriculum-sampling tests and CVs, effects varied across programs. Our findings highlight the need for continuous evaluation, identifying best practices within existing tools, and applying alternative tools.</p

Model-Based Selection for Proton Therapy in Breast Cancer:Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences

Aims: Proton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences. Materials and methods: A national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy. Results: The model of Darby et al. (N Engl J Med 2013; 368:987–82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021. Conclusion: The NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands