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5. Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity

Author

Bouma, R.G., primary, Nijen Twilhaar, M.K., additional, Brink, H., additional, Affandi, A.J., additional, Mesquita, B.S., additional, Olesek, K., additional, van Dommelen, J.M.A., additional, Heukers, R., additional, de Haas, A.M., additional, Kalay, H., additional, Ambrosini, M., additional, Metselaar, J.M., additional, van Rooijen, A., additional, Storm, G., additional, Oliveira, S., additional, van Kooyk, Y., additional, and den Haan, J.M.M., additional

Published
2024
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7. Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity

Author

Bouma, R. G., Twilhaar, M. K. Nijen, Brink, H. J., Affandi, A. J., Mesquita, B. S., Olesek, K., van Dommelen, J. M. A., Heukers, R., de Haas, A. M., Kalay, H., Ambrosini, M., Metselaar, J. M., van Rooijen, A., Storm, G., Oliveira, S., van Kooyk, Y., den Haan, J. M. M., Bouma, R. G., Twilhaar, M. K. Nijen, Brink, H. J., Affandi, A. J., Mesquita, B. S., Olesek, K., van Dommelen, J. M. A., Heukers, R., de Haas, A. M., Kalay, H., Ambrosini, M., Metselaar, J. M., van Rooijen, A., Storm, G., Oliveira, S., van Kooyk, Y., and den Haan, J. M. M.

Abstract

Cancer vaccines can be utilized in combination with checkpoint inhibitors to optimally stimulate the anti -tumor immune response. Uptake of vaccine antigen by antigen presenting cells (APCs) is a prerequisite for T cell priming, but often relies on non-specific mechanisms. Here, we have developed a novel vaccination strategy consisting of cancer antigen -containing liposomes conjugated with CD169- or DC -SIGN -specific nanobodies (single domain antibodies) to achieve specific uptake by APCs. Our studies demonstrate efficient nanobody liposome uptake by human and murine CD169 + and DC -SIGN + APCs in vitro and in vivo when compared to control liposomes or liposomes with natural ligands for CD169 and DC -SIGN. Uptake of CD169 nanobody liposomes resulted in increased T cell activation by human APCs and stimulated naive T cell priming in mouse models. In conclusion, while nanobody liposomes have previously been utilized to direct drugs to tumors, here we show that nanobody liposomes can be applied as vaccination strategy that can be extended to other receptors on APCs in order to elicit a potent immune response against tumor antigens.

Published
2024

11. Strong Lensing in Abell 1703: Constraints on the Slope of the Inner Dark Matter Distribution

Author

Limousin, M., Richard, J., Kneib, J. -P., Brink, H., Pello, R., Jullo, E., Tu, H., Sommer-Larsen, J., Egami, E., Michalowski, M. J., Cabanac, R., and Stark, D. P.

Subjects
Astrophysics
Abstract

In this article, we apply strong lensing techniques in Abell 1703, a massive X-ray luminous galaxy cluster at z=0.28. Our analysis is based on imaging data both from space and ground in 8 bands, complemented with a spectroscopic survey. Abell 1703 looks rather circular from the general shape of its multiply imaged systems and present a dominant giant elliptical cD galaxy in its centre. This cluster exhibits a remarkable bright 'central ring' formed by 4 bright images at z_{spec}=0.888 located very close to the cD galaxy, providing observational constraints that are potentially very interesting to probe the central mass distribution. The stellar contribution from the cD galaxy (~1.25 10^{12} M_{sun} within 7") is accounted for in our parametric mass modelling, and the underlying smooth dark matter component distribution is described using a generalized NFW profile parametrized with a central logarithmic slope \alpha. We find that within the range where observational constraints are present (from ~5" to ~50"), the slope of the dark matter distribution in Abell1703 is equal to 1.09^{+0.05}_{-0.11} (3\sigma confidence level). The concentration parameter is equal to c_{200} ~ 3.5, and the scale radius is constrained to be larger than the region where observational constraints are available. Within this radius, the 2D mass is equal to M(50")=2.4 10^{14} M_{\sun}. We cannot draw any conclusions on cosmological models at this point since we lack results from realistic numerical simulations containing baryons to make a proper comparison. We advocate the need for a sample of observed and simulated unimodal relaxed galaxy clusters in order to make reliable comparisons, and potentially provide a test of cosmological models., Comment: Accepted for publication, conclusion unchanged but strengthened by a serie of tests suggested by a constructive referee report. Higher resolution available at http://www.dark-cosmology.dk/~marceau/1703.php.html

Published
2008
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13. Atmospheric composition change – global and regional air quality

Author

Monks, PS, Granier, C, Fuzzi, S, Stohl, A, Williams, ML, Akimoto, H, Amann, M, Baklanov, A, Baltensperger, U, Bey, I, Blake, N, Blake, RS, Carslaw, K, Cooper, OR, Dentener, F, Fowler, D, Fragkou, E, Frost, GJ, Generoso, S, Ginoux, P, Grewe, V, Guenther, A, Hansson, HC, Henne, S, Hjorth, J, Hofzumahaus, A, Huntrieser, H, Isaksen, ISA, Jenkin, ME, Kaiser, J, Kanakidou, M, Klimont, Z, Kulmala, M, Laj, P, Lawrence, MG, Lee, JD, Liousse, C, Maione, M, McFiggans, G, Metzger, A, Mieville, A, Moussiopoulos, N, Orlando, JJ, O'Dowd, CD, Palmer, PI, Parrish, DD, Petzold, A, Platt, U, Pöschl, U, Prévôt, ASH, Reeves, CE, Reimann, S, Rudich, Y, Sellegri, K, Steinbrecher, R, Simpson, D, Brink, H ten, Theloke, J, van der Werf, GR, Vautard, R, Vestreng, V, Vlachokostas, Ch, and von Glasow, R

Subjects
Climate Action, Atmosphere, Troposphere, Air quality, Emissions, Climate, Co-benefit, Oxidation chemistry, Aerosols, Transport of pollutants, Ozone, Statistics, Atmospheric Sciences, Environmental Engineering, Meteorology & Atmospheric Sciences
Abstract

Air quality transcends all scales with in the atmosphere from the local to the global with handovers and feedbacks at each scale interaction. Air quality has manifold effects on health, ecosystems, heritage and climate. In this review the state of scientific understanding in relation to global and regional air quality is outlined. The review discusses air quality, in terms of emissions, processing and transport of trace gases and aerosols. New insights into the characterization of both natural and anthropogenic emissions are reviewed looking at both natural (e.g. dust and lightning) as well as plant emissions. Trends in anthropogenic emissions both by region and globally are discussed as well as biomass burning emissions. In terms of chemical processing the major air quality elements of ozone, non-methane hydrocarbons, nitrogen oxides and aerosols are covered. A number of topics are presented as a way of integrating the process view into the atmospheric context; these include the atmospheric oxidation efficiency, halogen and HOx chemistry, nighttime chemistry, tropical chemistry, heat waves, megacities, biomass burning and the regional hot spot of the Mediterranean. New findings with respect to the transport of pollutants across the scales are discussed, in particular the move to quantify the impact of long-range transport on regional air quality. Gaps and research questions that remain intractable are identified. The review concludes with a focus of research and policy questions for the coming decade. In particular, the policy challenges for concerted air quality and climate change policy (co-benefit) are discussed. © 2009 Elsevier Ltd.

Published
2009

17. The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis.

Author

Lam, B.Y.K., Cai, Y., Akinyemi, R., Biessels, G.J., Brink, H. van den, Chen, C, Cheung, C.W., Chow, K.N., Chung, H.K.H., Duering, M., Fu, S.T., Gustafson, D., Hilal, S., Hui, V.M.H., Kalaria, R., Kim, S., Lam, M.L.M., Leeuw, F.E. de, Li, A.S.M., Markus, H.S., Marseglia, A., Zheng, H., O'Brien, J., Pantoni, L., Sachdev, P.S., Smith, E.E., Wardlaw, J., Mok, V.C.T., Lam, B.Y.K., Cai, Y., Akinyemi, R., Biessels, G.J., Brink, H. van den, Chen, C, Cheung, C.W., Chow, K.N., Chung, H.K.H., Duering, M., Fu, S.T., Gustafson, D., Hilal, S., Hui, V.M.H., Kalaria, R., Kim, S., Lam, M.L.M., Leeuw, F.E. de, Li, A.S.M., Markus, H.S., Marseglia, A., Zheng, H., O'Brien, J., Pantoni, L., Sachdev, P.S., Smith, E.E., Wardlaw, J., and Mok, V.C.T.

Abstract

01 januari 2023, Item does not contain fulltext, BACKGROUND: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. AIM: This study aims to systematically review the prevalence of cSVD in LMICs. RESULTS: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes

Published
2023

18. Seasonality and competition select for variable germination behavior in perennials

Author

ten Brink, H., Haaland, T.R., Massol, F., Opedal, Ø.H., ten Brink, H., Haaland, T.R., Massol, F., and Opedal, Ø.H.

Abstract

The occurrence of within-population variation in germination behavior and associated traits such as seed size has long fascinated evolutionary ecologists. In annuals, unpredictable environments are known to select for bet-hedging strategies causing variation in dormancy duration and germination strategies. Variation in germination timing and associated traits is also commonly observed in perennials and often tracks gradients of environmental predictability. Although bet-hedging is thought to occur less frequently in long-lived organisms, these observations suggest a role of bet-hedging strategies in perennials occupying unpredictable environments. We use complementary analytical and evolutionary simulation models of within-individual variation in germination behavior in seasonal environments to show how bet-hedging interacts with fluctuating selection, life-history traits, and competitive asymmetries among germination strategies. We reveal substantial scope for bet-hedging to produce variation in germination behavior in long-lived plants, when “false starts” to the growing season results in either competitive advantages or increased mortality risk for alternative germination strategies. Additionally, we find that lowering adult survival may, in contrast to classic bet-hedging theory, result in less spreading of germination by decreasing density-dependent competition. These models extend insights from bet-hedging theory to perennials and explore how competitive communities may be affected by ongoing changes in climate and seasonality patterns.

Published
2023

19. Onzekerheidsanalyse GRADE Vecht

Author

Geertsema, T., Brink, H. van den, Velden, C. ten, Leander, R., Buitink, J., Geertsema, T., Brink, H. van den, Velden, C. ten, Leander, R., and Buitink, J.

Abstract

Dit rapport beschrijft de hoofdlijnen van de methode en resultaten van de onzekerheidsanalyse van GRADE Vecht (Generator of Rainfall and Discharge Extremes), waarbij uiteindelijk de afvoerstatistiek inclusief onzekerheden voor de Vecht bij Dalfsen wordt opgeleverd. De opgeleverde afvoerstatistiek inclusief onzekerheden is ontwikkeld voor gebruik in het Beoordelings- en Ontwerpinstrumentarium (BOI), waarmee wordt beoordeeld of de primaire keringen langs de Vecht aan de wettelijke normen voldoen.

Published
2023

20. Generator of Rainfall and Discharge Extremes (GRADE) voor de Vecht : Eindrapport

Author

Geertsema, T., Brink, H. van den, Velden, C. ten, Leander, R., Geertsema, T., Brink, H. van den, Velden, C. ten, and Leander, R.

Abstract

Dit rapport beschrijft de belangrijkste methodes en resultaten voor het opleveren van de afvoerstatistiek inclusief (uitgeïntegreerde) onzekerheden en golfvorm voor de Vecht bij Dalfsen. De tot nu toe gehanteerde afvoerstatistiek door Rijkswaterstaat en de aanliggende waterschappen voor de Overijsselse Vecht voor de beoordeling van de primaire waterkeringen is gebaseerd op statistische extrapolatie van de beschikbare afvoermetingen. Het nadeel is dat de kwaliteit van de afvoerstatistiek sterk afhankelijk is van de meetreeks, welke voor de Vecht qua lengte en kwaliteit zeer beperkt wordt beschouwd. Tevens zijn conclusies over afvoeren die hoger zijn dan die in de meetreeks voorkomen, betrouwbaarder met een op fysica gebaseerde methode dan een puur op metingen gebaseerde methode. Daarom is er sinds 2020 gewerkt aan het Generator of Rainfall and Discharge Extremes (GRADE) modelinstrumentarium voor de Vecht. GRADE is een combinatie van een stochastische Neerslaggenerator, een hydrologisch model en een hydrodynamisch model en wordt gebruikt voor het simuleren van extreme afvoeren in de Overijsselse Vecht bij Dalfsen. De ontwikkelingen van GRADE zijn gestart in 1998 voor de Rijn en de Maas en sinds 2014 worden GRADE Rijn en Maas officieel toegepast binnen het Wettelijk Beoordelings Instrumentarium (WBI2017) voor het genereren van de afvoerstatistiek en golfvorm. Deze methodiek biedt daarnaast mogelijkheden voor het verwerken van kennis over toekomstige ontwikkelingen, zoals klimaatverandering. In dit rapport wordt de methodiek en de resultaten gepresenteerd van de eerste versie van GRADE Vecht op basis van het huidige klimaat.

Published
2023

22. An audit of patients clinically deemed as high risk for malignant breast pathology at the Helen Joseph Hospital Breast Clinic

Author

Brink, H-M, Rubin, G, Benn, C-A, and Lucas, S

Subjects
malignant breast pathology, high risk patient, Helen Joseph Hospital Breast Clinic
Abstract

Background: The Helen Joseph Hospital Breast Clinic has implemented a clinical triage system for patients presenting with a variety of breast concerns. The goal of this system is to expedite the process from initial presentation to radiological assessment of patients with suspected breast malignancy or breast abscess in a resource limited setting. The objective was to assess the clinical, imaging and histological diagnoses of breast disease in these patients with malignancy and sepsis.Methods: A retrospective audit of patients clinically deemed high risk for malignant breast pathology referred to the breast imaging unit (BIU) in 2018. Patients were triaged based on strict clinical criteria: presence of a breast mass with or without lymph nodes or a breast abscess. Patients that were subsequently referred for mammography/ultrasound were identified using the patient files in the BIU. Results were recorded on Microsoft Excel and analysed using SAS version 9.2.Results: Three hundred and twenty-five patients were included in this study. Eighty-seven (26.8%) were diagnosed with breast cancer and 236 (72.6%) with benign disease. The most common presenting complaint was a palpable mass (n = 227; 69.9%). Ninety-five per cent of patients characterised as BI-RADS 5 had malignant disease. 55.8% of malignancies diagnosed on ultrasound had locally advanced disease. The most common histological diagnosis of malignancy was invasive ductal carcinoma (n = 67, 77%). The most commonly diagnosed benign disease was breast abscess (n = 42, 17.8%).Conclusion: BI-RADS findings correspond to similar studies, however, a large number of benign breast disease was diagnosed. This may indicate heightened clinical awareness of breast cancer diagnosis and early detection. A significant percentage of malignancies presented as locally advanced. Except for a lower number of invasive lobular carcinoma, the histological spectrum of malignant disease is similar to comparative studies.&nbsp

Published
2023

23. Scaling Propensity of Water

Author

van Raalte-Drewes, M., Brink, H., Feij, L., Slaats, P., van Soest, E., Vaal, P., and Veenendaal, G.

Subjects
scaling propensity water, thema EDItEUR::P Mathematics and Science::PD Science: general issues::PDG Industrial applications of scientific research and technological innovation, thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TQ Environmental science, engineering and technology::TQS Sanitary and municipal engineering::TQSW Water supply and treatment
Abstract

The commonly used Saturation Index calculated at 10°C (SI10) is not suitable for practical situations. New parameters have been developed for simple and rapid analysis of calcium carbonate precipitation (scaling) phenomena which occur during the heating of drinking water: TPCC90 (Theoretically Precipitable Calcium Carbonate at 90°C) SI90 (Saturation Index at 90°C) NI (Nucleation Index) PPCC (Practically Precipitable Calcium Carbonate) Both TPCC90 and SI90 describe the hydrodynamic driven force for the scaling reaction. The nucleation index indicates at what rate calcium carbonate precipitation is accelerated by nuclei present in the water. Finally, the PPCC is a measurement under practical conditions, determining the rate of scaling. The suitability of these parameters for predicting scaling was assessed and detailed results are presented in this publication.

Published
2004
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28. Practoraat : Onderzoekend leren en practoraten binnen Lentiz

Author

Brink, H. van den, Boerstoel, F., Franken, E., Dam, R. van, Brink, H. van den, Boerstoel, F., Franken, E., and Dam, R. van

Abstract

In deze publicatie laat Lentiz 4 voorbeelden zien waar onderzoekend leren in het mbo ten dienste staat van innovaties bij en met mkb-ondernemers.

Published
2022

29. Generator of Rainfall and Discharge Extremes for the Meuse : Final report of GRADE-Meuse version 3.0

Author

Hegnauer, M., Beersma, J., Brink, H. van den, Hegnauer, M., Beersma, J., and Brink, H. van den

Abstract

GRADE (Generation of Rainfall and Discharge Extremes) is een combinatie van een stochastische weergenerator, een hydrologisch model en een hydrodynamisch model en wordt gebruikt voor het simuleren van extreme afvoeren in de Maas bij Borgharen. De ontwikkelingen van GRADE zijn gestart in 1998 en sinds 2014 (versie GRADE 2.0) wordt GRADE officieel toegepast binnen het Wettelijk Beoordelings Instrumentarium (WBI2017) voor het genereren van de afvoerstatistiek en golfvorm. Sinds 2014 is er doorontwikkeld aan het GRADE instrumentarium om te komen tot een nieuwe versie (GRADE 3.0). In dit rapport worden deze nieuwe GRADE versie en de daaruit volgende resultaten gepresenteerd, inclusief de nieuwe afvoerstatistiek en golfvorm voor de Maas bij Borgharen. In het rapport worden de resultaten gepresenteerd voor het huidige klimaat., GRADE (Generation of Rainfall and Discharge Extremes) is a combination of a stochastic weather generator, a hydrological model, and a hydraulic model to simulate the discharge of the Meuse at Borgharen under extreme conditions. The development of GRADE started in 1998 and since 2014 GRADE (version 2.0) was implemented for the first time to derive discharge statistics and mean hydrograph shape for the Meuse at Borgharen. GRADE (version 2.0) was used for assessing the primary flood defense measures in the Netherlands (WBI2017). Since 2017 further development has been carried out leading to the new version GRADE 3.0. The goal of this report is to introduce the most recent update of the Generator of Rainfall and Discharge Extremes (GRADE) version 3.0 for the Meuse and to present the new results of discharge statistics and hydrograph shapes. This report presents the results of the GRADE 3.0 simulations for the Meuse at Borgharen for the current climate.

Published
2022

30. Generator of Rainfall and Discharge Extremes for the Rhine : Final report of GRADE-Rhine version 3.0

Author

Hegnauer, M., Beersma, J., Brink, H. van den, Leander, R., Hegnauer, M., Beersma, J., Brink, H. van den, and Leander, R.

Abstract

GRADE (Generation of Rainfall and Discharge Extremes) is een combinatie van een stochastische weergenerator, een hydrologisch model en een hydrodynamisch model en wordt gebruikt voor het simuleren van extreme afvoeren in de Rijn bij Lobith en de Maas bij Borgharen. De ontwikkelingen van GRADE zijn gestart in 1998 en sinds 2014 (versie GRADE 2.0) wordt GRADE officieel toegepast binnen het Wettelijk Beoordelings Instrumentarium (WBI2017) voor het genereren van de afvoerstatistiek en golfvorm. Sinds 2014 is er doorontwikkeld aan het GRADE instrumentarium om te komen tot een nieuwe versie (GRADE 3.0). In dit rapport worden deze nieuwe GRADE versie en de daaruit volgende resultaten gepresenteerd, inclusief de nieuwe afvoerstatistiek, de bijbehorende onzekerheidsband en de statistiek van golfvormen voor de Rijn bij Lobith., GRADE (Generation of Rainfall and Discharge Extremes) is a combination of a stochastic weather generator, a hydrological model, and a hydraulic model to simulate the discharge of the Rhine at Lobith under extreme conditions. The development of GRADE started in 1998 and since was applied for the first time in 2014 (GRADE version 2.0) to derive discharge statistics and mean hydrograph shape for the Rhine at Lobith. GRADE (version 2.0) was used in the assessment of the primary flood defense measures in the Netherlands (WBI2017). Since 2017 further development has been carried out leading to a new GRADE version (3.0). The goal of this report is to introduce the most recent update of the Generator of Rainfall and Discharge Extremes (GRADE) version 3.0 for the Rhine and to present the new results of discharge statistics (including uncertainties) and hydrograph shapes.

Published
2022

41. Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial

Author

Bosi, E, Choudhary, P, de Valk, H, Lablanche, S, Castaneda, J, de Portu, S, Da Silva, J, Re, R, Vorrink-de Groot, L, Shin, J, Kaufman, F, Cohen, O, Laurenzi, A, Caretto, A, Slatterly, D, Henderson-Wilson, M, Weisnagel, S, Dube, M, Julien, V, Trevisan, R, Lepore, G, Bellante, R, Hramiak, I, Spaic, T, Driscoll, M, Borot, S, Clergeot, A, Khiat, L, Hammond, P, Ray, S, Dinning, L, Tonolo, G, Manconi, A, Ledda, M, de Ranitz, W, Silvius, B, Wojtusciszyn, A, Farret, A, Vriesendorp, T, Immeker-de Jong, F, van der Linden, J, Brink, H, Alkemade, M, Schaepelynck-Belicar, P, Galie, S, Treglia, C, Benhamou, P, Haddouche, M, Hoogma, R, Leelarathna, L, Shaju, A, James, L, Bosi E., Choudhary P., de Valk H. W., Lablanche S., Castaneda J., de Portu S., Da Silva J., Re R., Vorrink-de Groot L., Shin J., Kaufman F. R., Cohen O., Laurenzi A., Caretto A., Slatterly D., Henderson-Wilson M., Weisnagel S. J., Dube M. -C., Julien V. -E., Trevisan R., Lepore G., Bellante R., Hramiak I., Spaic T., Driscoll M., Borot S., Clergeot A., Khiat L., Hammond P., Ray S., Dinning L., Tonolo G., Manconi A., Ledda M. S., de Ranitz W., Silvius B., Wojtusciszyn A., Farret A., Vriesendorp T., Immeker-de Jong F., van der Linden J., Brink H. S., Alkemade M., Schaepelynck-Belicar P., Galie S., Treglia C., Benhamou P. -Y., Haddouche M., Hoogma R., Leelarathna L., Shaju A., James L., Bosi, E, Choudhary, P, de Valk, H, Lablanche, S, Castaneda, J, de Portu, S, Da Silva, J, Re, R, Vorrink-de Groot, L, Shin, J, Kaufman, F, Cohen, O, Laurenzi, A, Caretto, A, Slatterly, D, Henderson-Wilson, M, Weisnagel, S, Dube, M, Julien, V, Trevisan, R, Lepore, G, Bellante, R, Hramiak, I, Spaic, T, Driscoll, M, Borot, S, Clergeot, A, Khiat, L, Hammond, P, Ray, S, Dinning, L, Tonolo, G, Manconi, A, Ledda, M, de Ranitz, W, Silvius, B, Wojtusciszyn, A, Farret, A, Vriesendorp, T, Immeker-de Jong, F, van der Linden, J, Brink, H, Alkemade, M, Schaepelynck-Belicar, P, Galie, S, Treglia, C, Benhamou, P, Haddouche, M, Hoogma, R, Leelarathna, L, Shaju, A, James, L, Bosi E., Choudhary P., de Valk H. W., Lablanche S., Castaneda J., de Portu S., Da Silva J., Re R., Vorrink-de Groot L., Shin J., Kaufman F. R., Cohen O., Laurenzi A., Caretto A., Slatterly D., Henderson-Wilson M., Weisnagel S. J., Dube M. -C., Julien V. -E., Trevisan R., Lepore G., Bellante R., Hramiak I., Spaic T., Driscoll M., Borot S., Clergeot A., Khiat L., Hammond P., Ray S., Dinning L., Tonolo G., Manconi A., Ledda M. S., de Ranitz W., Silvius B., Wojtusciszyn A., Farret A., Vriesendorp T., Immeker-de Jong F., van der Linden J., Brink H. S., Alkemade M., Schaepelynck-Belicar P., Galie S., Treglia C., Benhamou P. -Y., Haddouche M., Hoogma R., Leelarathna L., Shaju A., and James L.

Abstract

Background: Hypoglycaemia unawareness and severe hypoglycaemia can increase fear of hypoglycaemia and the risk of subsequent hypoglycaemic events. We aimed to assess the safety and efficacy of insulin pump therapy with integrated continuous glucose monitoring (CGM) and a suspend-before-low feature (Medtronic MiniMed 640G with SmartGuard) in hypoglycaemia-prone adults with type 1 diabetes. Methods: SMILE was an open-label randomised controlled trial done in people aged 24–75 years with type 1 diabetes for 10 years or longer, HbA1c values of 5·8–10·0% (40–86 mmol/mol), and at high risk of hypoglycaemia (recent severe hypoglycaemia or hypoglycaemia unawareness defined by a Clarke or Gold score ≥4). Participants were enrolled from 16 centres (eg, clinics, hospitals, or university medical centres) in Canada, France, Italy, the Netherlands, and the UK. After baseline run-in phase (2 weeks), participants were randomly assigned to the MiniMed 640G pump (continuous subcutaneous insulin infusion) with self-monitoring of blood glucose (control group) or to the MiniMed 640G system with the suspend-before-low feature enabled (intervention group), for 6 months. The study statistician analysing the data was masked to group assignment until final database lock; because of the nature of the intervention, participants and treating clinicians could not be masked to group assignment. The primary outcome was the mean number of sensor hypoglycaemic events, defined as 55 mg/dL (3·1 mmol/L) or lower, and was analysed on an intention-to-treat basis in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, number NCT02733991, and is completed. Findings: Between Dec 7, 2016, and March 27, 2018, 153 participants with a mean age 48·2 [12·4] years were randomly assigned: 77 to the control group (mean age 47·4 [12·5] years) and 76 to the intervention group (mean age 49·0 [12·2] years). After 6 months, the intervention group had significantly fewer hypoglycaemic even

Published
2019

42. A European aerosol phenomenology – 3: Physical and chemical characteristics of particulate matter from 60 rural, urban, and kerbside sites across Europe

Author

Putaud, J.-P., Van Dingenen, R., Alastuey, A., Bauer, H., Birmili, W., Cyrys, J., Flentje, H., Fuzzi, S., Gehrig, R., Hansson, H.C., Harrison, R.M., Herrmann, H., Hitzenberger, R., Hüglin, C., Jones, A.M., Kasper-Giebl, A., Kiss, G., Kousa, A., Kuhlbusch, T.A.J., Löschau, G., Maenhaut, W., Molnar, A., Moreno, T., Pekkanen, J., Perrino, C., Pitz, M., Puxbaum, H., Querol, X., Rodriguez, S., Salma, I., Schwarz, J., Smolik, J., Schneider, J., Spindler, G., ten Brink, H., Tursic, J., Viana, M., Wiedensohler, A., and Raes, F.

Published
2010
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43. Scaling Propensity of Water : New Predictive Parameters

Author

Brink, H., Slaats, P.G.G., Vaal, P.P.R., van Raalte-Drewes, M.J.C., Feij, L.A.C., van Soest, E.A.M., and Veenendaal, G.

Subjects
Science / Environmental Science, Technology & Engineering / Environmental / Water Supply
Abstract

The commonly used Saturation Index calculated at 10°C (SI10) is not suitable for practical situations. New parameters have been developed for simple and rapid analysis of calcium carbonate precipitation (scaling) phenomena which occur during the heating of drinking water: TPCC90 (Theoretically Precipitable Calcium Carbonate at 90°C) SI90 (Saturation Index at 90°C) NI (Nucleation Index) PPCC (Practically Precipitable Calcium Carbonate) Both TPCC90 and SI90 describe the hydrodynamic driven force for the scaling reaction. The nucleation index indicates at what rate calcium carbonate precipitation is accelerated by nuclei present in the water. Finally, the PPCC is a measurement under practical conditions, determining the rate of scaling. The suitability of these parameters for predicting scaling was assessed and detailed results are presented in this publication.

Published
2006

45. Impact of white matter hyperintensity location on depressive symptoms in memory-clinic patients

Author

Leeuwis, Anna E., Weaver, Nick A., Biesbroek, J. Matthijs, Exalto, L. G., Kuijf, Hugo J., Hooghiemstra, Astrid M., Prins, Niels D., Scheltens, Philip, Barkhof, Frederik, van der Flier, Wiesje M., Biessels, Geert Jan, Benedictus, M. R., Bremer, J., Leijenaar, J., Scheltens, P., Tijms, B. M., Wattjes, M. P., Teunissen, C. E., Koene, T., van den Berg, E., van den Brink, H., Boomsma, J. M. F., Ferro, D. A., Frijns, C. J. M., Groeneveld, O., Heinen, R., Heringa, S. M., Kappelle, L. J., Reijmer, Y. D., Verwer, J., de Bresser, J., Koek, H. L., Boss, H. M., Weinstein, H. C., Neurology, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, APH - Personalized Medicine, APH - Methodology, Immunology, and Pediatrics

Subjects
Male, medicine.medical_specialty, Population, Pyramidal Tracts, Neuroimaging, Comorbidity, computer.software_genre, Cohort Studies, White matter, 03 medical and health sciences, 0302 clinical medicine, Voxel, Internal medicine, medicine, Journal Article, Humans, Dementia, Cognitive Dysfunction, Pharmacology (medical), Cognitive decline, education, Geriatric Assessment, Biological Psychiatry, Aged, Psychiatric Status Rating Scales, education.field_of_study, 030214 geriatrics, Depression, business.industry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, Cerebrovascular Disorders, Psychiatry and Mental health, medicine.anatomical_structure, Corticospinal tract, Female, Geriatric Depression Scale, Biological psychiatry, business, computer, 030217 neurology & neurosurgery, Research Paper
Abstract

Background: We investigated the association between white matter hyperintensity location and depressive symptoms in a memoryclinic population using lesion–symptom mapping.Methods: We included 680 patients with vascular brain injury from the TRACE-VCI cohort (mean age ± standard deviation: 67 ± 8 years; 52% female): 168 patients with subjective cognitive decline, 164 with mild cognitive impairment and 348 with dementia. We assessed depressive symptoms using the Geriatric Depression Scale. We applied assumptionfree voxel-based lesion–symptom mapping, adjusted for age, sex, total white matter hyperintensity volume and multiple testing. Next, we applied exploratory region-of-interest linear regression analyses of major white matter tracts, with additional adjustment for diagnosis.Results: Voxel-based lesion–symptom mapping identified voxel clusters related to the Geriatric Depression Scale in the left corticospinal tract. Region-of-interest analyses showed no relation between white matter hyperintensity volume and the Geriatric Depression Scale, but revealed an interaction with diagnosis in the forceps minor, where larger regional white matter hyperintensity volume was associated with more depressive symptoms in subjective cognitive decline (β = 0.26, p < 0.05), but not in mild cognitive impairment or dementia.Limitations: We observed a lack of convergence of findings between voxel-based lesion–symptom mapping and region-of-interest analyses, which may have been due to small effect sizes and limited lesion coverage despite the large sample size. This warrants replication of our findings and further investigation in other cohorts.Conclusion: This lesion–symptom mapping study in depressive symptoms indicates the corticospinal tract and forceps minor as strategic tracts in which white matter hyperintensity is associated with depressive symptoms in memory-clinic patients with vascular brain injury. The impact of white matter hyperintensity on depressive symptoms is modest, but it appears to depend on the location of white matter hyperintensity and disease severity.

Published
2019
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46. Climate variability

Author

Weber, S. L., Guicherit, R., Den Brink, H. W., Dorland, R., Dijkstra, H., Greuell, W., Komen, G. J., Können, G., J Leeuwen, P., Plassche, O., Opsteegh, J. D., Ruiter, W. P. M., Selten, F. M., Ulden, A., Jef Vandenberghe, Berdowski, J., Guicherit, R., and Heij, B.J.

Published
2021
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47. Cerebral cortical microinfarcts in patients with internal carotid artery occlusion

Author

Brink, H. van den, Ferro, D.A., Bresser, J. de, Bron, E.E., Onkenhout, L.P., Kappelle, L.J., Biessels, G.J., Heart-Brain Connection Consortium, and Radiology & Nuclear Medicine

Subjects
Carotid Artery Diseases, Male, 0301 basic medicine, medicine.medical_specialty, chemical and pharmacologic phenomena, complex mixtures, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, Carotid Stenosis, In patient, Cognitive impairment, Aged, cerebral hemodynamic compromise, Cerebral hypoperfusion, business.industry, Original Articles, Cerebral blood flow, internal carotid artery occlusion, cerebrovascular disease, 030104 developmental biology, Neurology, Cerebrovascular Circulation, Cardiology, Female, Neurology (clinical), Internal carotid artery occlusion, Cardiology and Cardiovascular Medicine, business, microinfarct, Carotid Artery, Internal, 030217 neurology & neurosurgery
Abstract

Cerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise. We included 95 patients with a complete ICA occlusion (age 66.2 ± 8.3, 22% female) and 125 reference participants (age 65.5 ± 7.4, 47% female). Participants underwent clinical, neuropsychological, and 3 T brain MRI assessment. CMI were more common in patients with an ICA occlusion (54%, median 2, range 1–33) than in the reference group (6%, median 0; range 1–7; OR 14.3; 95% CI 6.2–33.1; p

Published
2021

48. Meerwaarde KNMI-lange-modelreeksen-aanpak voor BOI2023 : Een nieuwe methode voor het afleiden van BOI-Belastingstatistieken

Author

Brink, H. van den, Bottema, M., Brink, H. van den, and Bottema, M.

Abstract

Afgelopen jaren hebben KNMI en Deltares in samenwerking met RWS WVL ten behoeve van het beoordelingsinstrumentarium voor de primaire waterkeringen veel werk verzet voor het verbeteren van de extreme-wind-statistiek en ruimtelijke windmodellering. Bij gebrek aan voldoende metingen waren in eerste instantie onvoldoende verbeteringen haalbaar. Daarom heeft KNMI een nieuwe aanpak ontwikkeld, op basis van zeer lange KNMI-modelreeksen. In de jaren 2019 en 2020 zijn een proef-of-concept ontwikkeld, en een plan van aanpak voor de uitrol ervan. Het huidige Meerwaardedocument is geschreven ter ondersteuning van die uitrol. Daarnaast gaat dit rapport in op aanvullende toepassingen van de methode, en hun meerwaarde. Het huidige rapport is primair bedoeld als businesscase-beschrijving, voor verdere achtergronden wordt verwezen naar de in dit rapport genoemde literatuurreferenties.

Published
2021

49. Exploring high-end scenarios for local sea level rise to develop flood protection strategies for a low-lying delta—the Netherlands as an example

Author

Katsman, Caroline A., Sterl, A., Beersma, J. J., van den Brink, H. W., Church, J. A., Hazeleger, W., Kopp, R. E., Kroon, D., Kwadijk, J., Lammersen, R., Lowe, J., Oppenheimer, M., Plag, H. -P., Ridley, J., von Storch, H., Vaughan, D. G., Vellinga, P., Vermeersen, L. L. A., van de Wal, R. S. W., and Weisse, R.

Published
2011
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