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

What drives amyloid molecules to assemble into oligomers and fibrils?

We develop a general theory for three states of equilibrium of amyloid peptides: the monomer, oligomer, and fibril. We assume that the oligomeric state is a disordered micelle-like collection of a few peptide chains held together loosely by hydrophobic interactions into a spherical hydrophobic core. We assume that fibrillar amyloid chains are aligned and further stabilized by `steric zipper' interactions -- hydrogen bonding and steric packing, in addition to specific hydrophobic sidechain contacts. The model makes a broad set of predictions, consistent with experiments: (i) Similar to surfactant micellization, amyloid oligomerization should increase with bulk peptide concentration. (ii) The onset of fibrillization limits the concentration of oligomers in the solution. (iii) The average fibril length \emph{vs.} monomer concentration agrees with data on $\alpha$-synuclein, (iv) Full fibril length distributions follow those of $\alpha$-synuclein, (v) Denaturants should `melt out' fibrils, and (vi) Added salt should stabilize fibrils by reducing repulsions between amyloid peptide chains. Interestingly, small changes in solvent conditions can: (a) tip the equilibrium balance between oligomer and fibril, and (b) cause large changes in rates, through effects on the transition-state barrier. This model may provide useful insights into the physical processes underlying amyloid diseases

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

Rapid neuronal differentiation of induced pluripotent stem cells for measuring network activity on micro-electrode arrays

Neurons derived from human induced Pluripotent Stem Cells (hiPSCs) provide a promising new tool for studying neurological disorders. In the past decade, many protocols for differentiating hiPSCs into neurons have been developed. However, these protocols are often slow with high variability, low reproducibility, and low efficiency. In addition, the neurons obtained with these protocols are often immature and lack adequate functional activity both at the single-cell and network levels unless the neurons are cultured for several months. Partially due to these limitations, the functional properties of hiPSC-derived neuronal networks are still not well characterized. Here, we adapt a recently published protocol that describes production of human neurons from hiPSCs by forced expression of the transcription factor neurogenin-212. This protocol is rapid (yielding mature neurons within 3 weeks) and efficient, with nearly 100% conversion efficiency of transduced cells (>95% of DAPI-positive cells are MAP2 positive). Furthermore, the protocol yields a homogeneous population of excitatory neurons that would allow the investigation of cell-type specific contributions to neurological disorders. We modified the original protocol by generating stably transduced hiPSC cells, giving us explicit control over the total number of neurons. These cells are then used to generate hiPSC-derived neuronal networks on micro-electrode arrays. In this way, the spontaneous electrophysiological activity of hiPSC-derived neuronal networks can be measured and characterized, while retaining interexperimental consistency in terms of cell density. The presented protocol is broadly applicable, especially for mechanistic and pharmacological studies on human neuronal networks

Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions

Smoking Cessation has no Influence on Quality of Life in Patients with Peripheral Arterial Disease 5 Years Post-vascular Surgery

AbstractObjectivesSmoking is an important modifiable risk factor in patients with peripheral arterial disease (PAD). We investigated differences in quality of life (QoL) between patients who quitted smoking during follow-up and persistent smokers.DesignCohort study.MethodsData of 711 consecutively enrolled patients undergoing vascular surgery were collected in 11 hospitals in the Netherlands. Smoking status was obtained at baseline and at 3-year follow-up. A 5-year follow-up to measure QoL was performed with the EuroQol-5D (EQ-5D) and Peripheral Arterial Questionnaire (PAQ).ResultsAfter adjusting for clinical risk factors, patients, who quit smoking within 3 years after vascular surgery, did not report an impaired QoL (EQ-5D: odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.28–1.43; PAQ: OR = 0.76, 95% CI = 0.35–1.65; visual analogue scale (VAS): OR = 0.88, 95% CI = 0.42–1.84) compared with patients, who continued smoking. Current smokers were significantly more likely to have an impaired QoL (EQ-5D: OR = 1.86, 95% CI = 1.09–3.17; PAQ: OR = 1.63, 95% CI = 1.00–2.65), although no differences in VAS scores were found (OR = 1.17, 95% CI = 0.72–1.90).ConclusionsThere was no effect of smoking cessation on QoL in PAD patients undergoing vascular surgery. Nevertheless, given the link between smoking, complications and mortality in this patient group, smoking cessation should be a primary target in secondary prevention

Machining of ceramics and ecological steels using a mill-turn centre equipped with an ultrasonic assisted tooling system

Abstract Today, there is a large demand for the machining of simple and/or complex shaped components made of difficult to cut materials such as ceramics. Recently, there is also a demand to machine new type of steels, having restrictions in chemical composition (e.g. lead and sulphur free) in order to comply with recent governmental EU regulations. This paper first describes on-going and planned research activities on the machining (turning) of these advanced materials. For the machining of various ceramic materials, an ultrasonic assisted tooling system has been designed, manufactured and integrated within the available Mori Seiki NL2000Y/500 mill-turn centre. The developed system has been tested through initial machining experiments on aluminium and ZrO 2 . Second, this paper also briefly describes other on-going and planned research and education activities in which the Mori Seiki NL2000Y/500 is involved. It includes advanced NCprogramming of multi-axis machine tools, energy efficient machining of ecological steels and the development of training programs for 3 rd years mechanical engineering students

How does nudging the COVID-19 vaccine play out in people who are in doubt about vaccination?

In spite of the growing availability of COVID-19 vaccines, a substantial number of people is reluctant or uncertain about getting the vaccine. Nudges may improve vaccine uptake but it is unclear how this plays out with the experience of autonomous choice, decision competence, decision satisfaction, and being pressured to make a choice. In an online experiment among a representative sample (N = 884), we examined whether a social norm nudge or a default nudge (either or not transparent) was effective in steering the desired choice of making a hypothetical early vaccination appointment as compared to making a later appointment or no appointment. We also examined how both nudges affected autonomy and related downstream consequences. None of the nudges proved effective in making the desired choice of early vaccination and neither did they impact on downstream consequences. Rather, our results indicate that participants who were certain about their choice (i.e., opted for the earliest available vaccination opportunity or not getting vaccinated at all) reported higher levels of autonomy, competence and satisfaction than participants who did not know yet about vaccination or who postponed the moment of getting their vaccination. We conclude that the experience of autonomy and related downstream consequences is determined by having made up one's mind about vaccination, and is not affected by attempts to nudge the individual. Public Health and primary carePrevention, Population and Disease management (PrePoD

Beta-blockers and health-related quality of life in patients with peripheral arterial disease and COPD

Yvette RBM van Gestel1, Sanne E Hoeks1, Don D Sin2, Henk Stam3, Frans W Mertens3, Jeroen J Bax4, Ron T van Domburg5, Don Poldermans61Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands; 2Department of Medicine, University of British Columbia and The James Hogg iCAPTURe Center, St. Paul’s Hospital, Vancouver, Canada; 3Department of Pulmonology, Erasmus Medical Center, Rotterdam, The Netherlands; 4Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 5Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands; 6Department of Vascular Surgery, Erasmus Medical Center, Rotterdam, The NetherlandsBackground: Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD) because of concerns that they might provoke bronchospasm and cause deterioration in health status. Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown. The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL) in patients with peripheral arterial disease and COPD.Methods: Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up. These COPD patients were sent the Short Form-36 (SF-36) health-related quality of life questionnaire, which was completed and returned by 326 (70%) patients.Results: No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all). Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD.Conclusion: Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD. This suggests that beta-blockers can, in most circumstances, be administered to patients with COPD without impairment in HRQOL. Keywords: beta-blockers, chronic obstructive pulmonary disease, vascular surgery, health-related quality of lif

Changes in disease characteristics and response rates among patients in the United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid arthritis between 2001 and 2008

Objectives. Anti-TNF therapy has significantly improved outcomes for patients with severe RA. In the UK, changing financial restrictions and increasing experience with their use may have resulted in changes to the way physicians use anti-TNF therapies. The aim of this analysis was to examine changes in disease characteristics and response rates among patients starting anti-TNF therapy for RA over an 8-year period