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UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl)

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The inflammable truth of atherosclerosis

Verweij, S.L.

Publication date

2018

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Citation for published version (APA):

Verweij, S. L. (2018). The inflammable truth of atherosclerosis.

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About the author

ĂŶŬǁŽŽƌĚ

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is een suiker analoog en suiker is de brandstof voor de stofwisseling in het lichaam. KŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ŚĞďďĞŶ ĞĞŶ ŚŽŐĞ ƐƚŽĨǁŝƐƐĞůŝŶŐ͕ ĚƵƐ ŝŶĚŝĞŶ Ğƌ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ĂĐƟĞĨ njŝũŶ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ͕ njƵůůĞŶ ĚĞnjĞ ĐĞůůĞŶ ǀĞĞů &' ŽƉŶĞŵĞŶ͘ DĞƚ ĞĞŶ Wdͬd ƐĐĂŶ ŬĂŶ ǁŽƌĚĞŶŐĞŵĞƚĞŶŚŽĞǀĞĞů&'ĞƌǁŽƌĚƚŽƉŐĞŶŽŵĞŶŝŶďŝũǀŽŽƌďĞĞůĚĚĞǀĂĂƚǁĂŶĚ͕ĚĞƐƚĞ ŚŽŐĞƌĚĞ&'ͲŽƉŶĂŵĞŝŶĚĞǀĂĂƚǁĂŶĚ͕ĚĞƐƚĞŵĞĞƌŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŚŝĞƌĂĂŶǁĞnjŝŐnjŝũŶ͘ InŚŽŽĨĚƐƚƵŬϮhebben we eerst gekeken naar de betrouwbaarheid en reproduceerbaarheid

ǀĂŶ ǀĞƌƐĐŚŝůůĞŶĚĞ ŵĞƚŚŽĚĞŶ Žŵ &'ͲŽƉŶĂŵĞ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ ƚĞ ŵĞƚĞŶ͘ ĂĂƌŶĂ ŚĞďďĞŶ ǁĞŽŶĚĞƌnjŽĐŚƚǁĂŶŶĞĞƌĞƌƐƉƌĂŬĞŝƐǀĂŶǀĞƌŚŽŽŐĚĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚŝŶĚĞǀĂĂƚǁĂŶĚ͘ ,ŝĞƌǀŽŽƌŚĞďďĞŶǁĞ&'ͲŽƉŶĂŵĞŐĞŵĞƚĞŶŝŶĚĞŚĂůƐƐůĂŐĂĚĞƌĞŶĚĞŐƌŽƚĞůŝĐŚĂĂŵƐƐůĂŐĂĚĞƌ ŝŶnjŽǁĞůŐĞnjŽŶĚĞĐŽŶƚƌŽůĞƉĞƌƐŽŶĞŶĂůƐŝŶƉĂƟģŶƚĞŶŵĞƚŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶŽĨŵĞƚĞĞŶ

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EĞĚĞƌůĂŶĚƐĞƐĂŵĞŶǀĂƫŶŐ ǀĞƌŚŽŽŐĚĐĂƌĚŝŽǀĂƐĐƵůĂŝƌƌŝƐŝĐŽƉƌŽĮĞů͘ŽŽƌĚĞ&'ͲŽƉŶĂŵĞŝŶĚĞŐĞnjŽŶĚĞĐŽŶƚƌŽůĞƉĞƌƐŽŶĞŶ ĂůƐ͚ŶŽƌŵĂĂů͛ƚĞďĞŽŽƌĚĞůĞŶ͕ŝƐĞƌĞĞŶĚƌĞŵƉĞůǁĂĂƌĚĞďĞƉĂĂůĚ;ǁĞĞƌŐĞŐĞǀĞŶĂůƐƚĂƌŐĞƚͲƚŽͲ ďĂĐŬŐƌŽƵŶĚƌĂƟŽ;dZͿͿĚŝĞǁĞĞƌŐĞĞŌŽĨƐƉƌĂŬĞŝƐǀĂŶǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ͘,ĞƚŵĞƌĞŶĚĞĞů ǀĂŶĚĞƉĂƟģŶƚĞŶŵĞƚŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶŽĨŵĞƚĞĞŶǀĞƌŚŽŽŐĚĐĂƌĚŝŽǀĂƐĐƵůĂŝƌƌŝƐŝĐŽƉƌŽĮĞů ŚĞďďĞŶ ŵĞĞƌ &'ͲŽƉŶĂŵĞ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ ĚĂŶ ĚĞ ĞĞƌĚĞƌ ďĞƉĂĂůĚĞ ĚƌĞŵƉĞůǁĂĂƌĚĞ ĞŶ ĚĞnjĞƉĂƟģŶƚĞŶŚĞďďĞŶǀŽůŐĞŶƐĚĞnjĞŵĞƚŚŽĚĞĚƵƐĞĞŶǀĞƌŚŽŽŐĚĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚŝŶ ĚĞǀĂĂƚǁĂŶĚ͘ĞnjĞĚƌĞŵƉĞůǁĂĂƌĚĞnjŽƵŝŶĚĞƚŽĞŬŽŵƐƚŐĞďƌƵŝŬƚŬƵŶŶĞŶǁŽƌĚĞŶǀŽŽƌŚĞƚ ďĞƉĂůĞŶ ǀĂŶ ĚĞ ŵĂƚĞ ǀĂŶ ǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ ŝŶ ƉĂƟģŶƚĞŶ ĚŝĞ ĚĞĞůŶĞŵĞŶ ĂĂŶ ƐƚƵĚŝĞƐ͕ ŝŶĚŝĞŶĚĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚŝŶďĞŝĚĞƐƚƵĚŝĞƐŽƉĚĞnjĞůĨĚĞŵĂŶŝĞƌŐĞŵĞƚĞŶŝƐ͘ ,ŽŽĨĚƐƚƵŬ ϯ ĞŶ ϰ ďĞƐĐŚƌŝũǀĞŶ ŶŝĞƚ ĂůůĞĞŶ ŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ͕ ŵĂĂƌ ŽŽŬ ǀĞƌŚŽŽŐĚĞĂĐƟǀŝƚĞŝƚŝŶŽƌŐĂŶĞŶĚŝĞĚĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶƉƌŽĚƵĐĞƌĞŶ͕ŶĂŵĞůŝũŬŚĞƚďĞĞŶŵĞƌŐ en de milt. In ŚŽŽĨĚƐƚƵŬϯƚŽŶĞŶǁŝũĚŽŽƌŵŝĚĚĞůǀĂŶWdͬdǀĞƌŚŽŽŐĚĞǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ ĞŶ ǀĞƌŚŽŽŐĚĞ &'ͲŽƉŶĂŵĞ ŝŶ ŚĞƚ ďĞĞŶŵĞƌŐ ĞŶ ĚĞ ŵŝůƚ ŝŶ ƉĂƟģŶƚĞŶ ŵĞƚ ŚĂƌƚͲ ĞŶ vaatziekten. Aangezien beenmerg en milt betrokken zijn bij de aanmaak van bloedcellen ;ǁĂĂƌŽŶĚĞƌ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶͿ ǁŝũƐƚ ĚĞ ǀĞƌŚŽŽŐĚĞ &'ͲŽƉŶĂŵĞ ŝŶ ĚĞnjĞ ŽƌŐĂŶĞŶ ŽƉ ĞĞŶ ŐƌŽƚĞƌĞ ĂĂŶŵĂĂŬ ŽĨ ŐƌŽĞŝ ǀĂŶ ďůŽĞĚǀŽƌŵĞŶĚĞ ƐƚĂŵĐĞůůĞŶ͕ ŽŽŬ ǁĞů ,^WƐ ŐĞŶŽĞŵĚ͘ Kŵ ĚĞnjĞŚLJƉŽƚŚĞƐĞƚĞŽŶĚĞƌƐƚĞƵŶĞŶ͕ŚĞďďĞŶǁĞŝŶŚĞƚůĂďŽƌĂƚŽƌŝƵŵĂĂŶŐĞƚŽŽŶĚĚĂƚĚĞ,^WƐ ǀĂŶƉĂƟģŶƚĞŶŵĞƚŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶĞĞŶǀĞƌŚŽŽŐĚĞĐĂƉĂĐŝƚĞŝƚƚŽƚĚĞůŝŶŐŚĞďďĞŶʹĞŶ ĚĂĂƌŵĞĞĚƵƐĞĞŶŐƌŽƚĞƌĞŐƌŽĞŝĐĂƉĂĐŝƚĞŝƚ͘ĞnjĞĚĂƚĂůĂƚĞŶnjŝĞŶĚĂƚŶŝĞƚĂůůĞĞŶĚĞǀĂĂƚǁĂŶĚ͕ ŵĂĂƌŽŽŬŚĞƚďĞĞŶŵĞƌŐĞŶĚĞŵŝůƚďĞƚƌŽŬŬĞŶnjŝũŶďŝũĚĞŽŶƚƐƚĞŬŝŶŐƐƌĞĂĐƟĞŝŶƉĂƟģŶƚĞŶŵĞƚ hart- en vaatziekten. In ŚŽŽĨĚƐƚƵŬϰďĞƐĐŚƌŝũǀĞŶǁĞŚĞƚĚŝƌĞĐƚĞĞīĞĐƚǀĂŶĞĞŶŚĂƌƟŶĨĂƌĐƚ͕ ĞĞŶĂĐƵƚĞĂĨƐůƵŝƟŶŐǀĂŶĞĞŶďůŽĞĚǀĂƚ͕ŽƉŚĞƚďĞĞŶŵĞƌŐĞŶĚĞŵŝůƚ͘,ĞƚŝƐďĞŬĞŶĚĚĂƚĚŽŽƌ ĚĞƐƚƌĞƐƐǀĂŶĞĞŶŚĂƌƟŶĨĂƌĐƚŚĞƚďĞĞŶŵĞƌŐĞŶĚĞŵŝůƚŐĞĂĐƟǀĞĞƌĚǁŽƌĚĞŶ͕ǁĂĂƌĚŽŽƌĚĞ ƉƌŽĚƵĐƟĞ ǀĂŶ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ŽŵŚŽŽŐ ŐĂĂƚ͘ ,Ğƚ ŝƐ ĞĐŚƚĞƌ ŶŝĞƚ ďĞŬĞŶĚ ŚŽĞ ůĂŶŐ ĚĞnjĞ ƌĞĂĐƟĞĂĂŶŚŽƵĚƚ͘/ŶĚĞnjĞƐƚƵĚŝĞŚĞďďĞŶǁĞŐĞďƌƵŝŬŐĞŵĂĂŬƚǀĂŶĞĞŶĂŶĚĞƌĞƌĂĚŝŽĂĐƟĞǀĞ ƚƌĂĐĞƌǀŽŽƌWdͬd͕ŶĂŵĞůŝũŬWͲϳϭϰ͘ĂŶŐĞnjŝĞŶ&'ĞĞŶƐƵŝŬĞƌĂŶĂůŽŽŐŝƐ͕ŝƐ&'ͲŽƉŶĂŵĞ ŝŶďĞĞŶŵĞƌŐĞŶŵŝůƚĞĞŶĂĨƐƉŝĞŐĞůŝŶŐǀĂŶĚĞƐƚŽĨǁŝƐƐĞůŝŶŐŝŶĚĞnjĞŽƌŐĂŶĞŶ͘WͲϳϭϰŝƐĞĐŚƚĞƌ ĞĞŶ ƚƌĂĐĞƌ ĚŝĞ ƐƉĞĐŝĮĞŬ ďŝŶĚƚ ĂĂŶ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ĞŶ ŚŝĞƌŵĞĞ ŬĂŶ ĚƵƐ ĚĞ ŚŽĞǀĞĞůŚĞŝĚ ontstekingscellen in het beenmerg en de milt worden aangetoond in plaats van alleen de algemene mate van stofwisseling in deze organen. Wij laten in dit hoofdstuk zien dat in de ĂĐƵƚĞĨĂƐĞŶĂĞĞŶŚĂƌƟŶĨĂƌĐƚƉĂƟģŶƚĞŶŵĞĞƌŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŝŶŚĞƚďĞĞŶŵĞƌŐĞŶĚĞŵŝůƚ ŚĞďďĞŶǀĞƌŐĞůĞŬĞŶŵĞƚŐĞnjŽŶĚĞĐŽŶƚƌŽůĞƉĞƌƐŽŶĞŶ͘ŝƚŐĂĂƚƐĂŵĞŶŵĞƚĞĞŶŚŽŐĞƌĂĂŶƚĂů ,^WƐ ŝŶ ŚĞƚ ďůŽĞĚ ĞŶ ĞĞŶ ŚŽŐĞƌ ĂĂŶƚĂů ;ĞŶ ĂĐƟĞǀĞƌĞͿ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ;ŵŽŶŽĐLJƚĞŶͿ͘ sĞƌĚĞƌ ůĂƚĞŶ ǁĞ njŝĞŶ ĚĂƚ ĚĞnjĞ ƌĞĂĐƟĞ ŽŽŬ ĚƌŝĞ ŵĂĂŶĚĞŶ ŶĂ ŚĞƚ ŝŶĨĂƌĐƚ ŶŽŐ ĂĂŶǁĞnjŝŐ ŝƐ͘ ĐŚƚĞƌ͕ŚĞƚůŝũŬƚĞƌŽƉĚĂƚŶĂĚƌŝĞŵĂĂŶĚĞŶĚĞƉƌŽĚƵĐƟĞǀĂŶĚĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶǀŽŽƌĂůĚŽŽƌ ĚĞŵŝůƚǁŽƌĚƚŽǀĞƌŐĞŶŽŵĞŶ͕ĂĂŶŐĞnjŝĞŶĚĞWͲŽƉŶĂŵĞŝŶŚĞƚďĞĞŶŵĞƌŐŶĂĚƌŝĞŵĂĂŶĚĞŶ gedaald is.

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ĞnjĞĚĂƚĂƚŽŶĞŶĂĂŶĚĂƚĞƌĚƌŝĞŵĂĂŶĚĞŶŶĂĞĞŶŚĂƌƟŶĨĂƌĐƚŶŽŐĞĞŶǀĞƌŚŽŽŐĚĞĂĐƟǀŝƚĞŝƚ ǀĂŶŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶƉƌŽĚƵĐĞƌĞŶĚĞŽƌŐĂŶĞŶŝƐ͕ǁĂƚůĞŝĚƚƚŽƚĞĞŶǀĞƌŚŽŽŐĚĞƉƌŽĚƵĐƟĞǀĂŶ ĚĞnjĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ͘ĞnjĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŬƵŶŶĞŶĚĂŶǁĞĞƌĚĞǀĂĂƚǁĂŶĚŝŶďĞǁĞŐĞŶ͕ ǁĂĂƌ njĞ ĚĞ Ăů ĂĂŶǁĞnjŝŐĞ ǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ ŬƵŶŶĞŶ ĂĂŶǁĂŬŬĞƌĞŶ͘ ŝƚ ŬĂŶ ĞĞŶ ǀĂŶ ĚĞ ƌĞĚĞŶĞŶnjŝũŶǁĂĂƌŽŵƉĂƟģŶƚĞŶŶĂĞĞŶŚĂƌƟŶĨĂƌĐƚĞĞŶŐƌŽŽƚƌŝƐŝĐŽŚĞďďĞŶŽƉĞĞŶŶŝĞƵǁ infarct. /ŶŚĞƚůĂĂƚƐƚĞŚŽŽĨĚƐƚƵŬǀĂŶŚĞƚĞĞƌƐƚĞĚĞĞů͕ŚŽŽĨĚƐƚƵŬϱ͕ǁŽƌĚƚĚĞƌĞůĂƟĞďĞƐĐŚƌĞǀĞŶƚƵƐƐĞŶ ĚĞĞdžƉƌĞƐƐŝĞǀĂŶZϮŽƉĞĞŶǀĂŶĚĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ͕ĚĞŵŽŶŽĐLJƚ͕ĞŶǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ͘ ZϮ ŝƐ ĞĞŶĞŝǁŝƚ ŽƉ ĚĞŵŽŶŽĐLJƚĚŝĞ ďĞůĂŶŐƌŝũŬ ŝƐ ǀŽŽƌ ĚĞďĞǁĞŐŝŶŐǀĂŶ ĚĞnjĞĐĞůǀĂŶƵŝƚ ŚĞƚ ďůŽĞĚ ŶĂĂƌ ĚĞ ǀĂĂƚǁĂŶĚ͘ tŝũ ƚŽŶĞŶ ĂĂŶ ĚĂƚ Ğƌ ĞĞŶ ƌĞůĂƟĞ ŝƐ ƚƵƐƐĞŶ ĚĞ ŚŽĞǀĞĞůŚĞŝĚ ǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐĞŶZϮͲĞdžƉƌĞƐƐŝĞŽƉĚĞŵŽŶŽĐLJƚ͕ŽŶĂĬĂŶŬĞůŝũŬǀĂŶƌŝƐŝĐŽĨĂĐƚŽƌĞŶŽƉ ŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶĞŶŽŶĂĬĂŶŬĞůŝũŬǀĂŶƐƚĂƟŶĞŐĞďƌƵŝŬ͘ŝƚďĞƚĞŬĞŶƚĚĂƚZϮĞdžƉƌĞƐƐŝĞ ŽƉŵŽŶŽĐLJƚĞŶĞĞŶďĞůĂŶŐƌŝũŬĞƌŽůƐƉĞĞůƚďŝũĚĞŽŶƚǁŝŬŬĞůŝŶŐǀĂŶǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ͘,Ğƚ ŽŶĚĞƌĚƌƵŬŬĞŶǀĂŶZϮĞdžƉƌĞƐƐŝĞŽƉŵŽŶŽĐLJƚĞŶnjŽƵŝŶĚĞƚŽĞŬŽŵƐƚĞĞŶĂĂŶŐƌŝũƉŝŶŐƐƉƵŶƚ kunnen zijn voor nieuwe behandelingen van hart- en vaatziekten.

ĞĞů // ǀĂŶ Ěŝƚ ƉƌŽĞĨƐĐŚƌŝŌ ďĞƐĐŚƌŝũŌ ĂŶĚĞƌĞ ĨĂĐƚŽƌĞŶ͕ ŶĂĂƐƚ ŚĞƚ >> ĐŚŽůĞƐƚĞƌŽů͕ ĚŝĞ

ďŝũĚƌĂŐĞŶĂĂŶĚĞŽŶƚƐƚĞŬŝŶŐƐƌĞĂĐƟĞŝŶĚĞǀĂĂƚǁĂŶĚŝŶƉĂƟģŶƚĞŶŵĞƚŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶ͘ EŝĞƚĂůůĞĞŶ>>ĐŚŽůĞƐƚĞƌŽůŬĂŶĂƚŚĞƌŽƐĐůĞƌŽƐĞǀĞƌŽŽƌnjĂŬĞŶ͕ŵĂĂƌŽŽŬǀĞƌŚŽŽŐĚƌĞŵŶĂŶƚ ĐŚŽůĞƐƚĞƌŽů ŬĂŶ ůĞŝĚĞŶ ƚŽƚ ĂƚŚĞƌŽƐĐůĞƌŽƐĞ͘ ZĞŵŶĂŶƚ ĐŚŽůĞƐƚĞƌŽů ŝƐ ŚĞƚ ŽǀĞƌŝŐĞ ĐŚŽůĞƐƚĞƌŽů ŶĂĂƐƚ ŚĞƚ ,> ;ŐŽĞĚ ĐŚŽůĞƐƚĞƌŽůͿ ĞŶ >> ĐŚŽůĞƐƚĞƌŽů͘ /Ŷ ŚŽŽĨĚƐƚƵŬ ϲ tonen we aan dat ƉĂƟģŶƚĞŶ ŵĞƚ ǀĞƌŚŽŽŐĚ ƌĞŵŶĂŶƚ ĐŚŽůĞƐƚĞƌŽů ŵĞĞƌ ŽŶƚƐƚĞŬŝŶŐ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ ŚĞďďĞŶ ǀĞƌŐĞůĞŬĞŶŵĞƚŐĞnjŽŶĚĞĐŽŶƚƌŽůĞƉĞƌƐŽŶĞŶ͘ĂĂƌŶĂĂƐƚůĂƚĞŶǁĞnjŝĞŶĚĂƚĚĞnjĞƉĂƟģŶƚĞŶŶŝĞƚ ĂůůĞĞŶĞĞŶǀĞƌŚŽŽŐĚĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚŝŶĚĞǀĂĂƚǁĂŶĚŚĞďďĞŶ͕ŵĂĂƌŽŽŬĚĂƚĞƌŵĞĞƌ ĞŶĂĐƟĞǀĞƌĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŝŶŚĞƚďůŽĞĚĂĂŶǁĞnjŝŐnjŝũŶ͘ĞnjĞŽďƐĞƌǀĂƟĞůĂĂƚnjŝĞŶĚĂƚĚĞ ďĂƐŝƐǀŽŽƌĚĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚŝŶĚĞǀĂĂƚǁĂŶĚĂůŐĞůĞŐĚǁŽƌĚƚŝŶĚĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ŝŶ ŚĞƚ ďůŽĞĚ͘ dĞŶ ƐůŽƩĞ ƚŽŶĞŶ ǁĞ ŽŽŬ ĞĞŶ ǀĞƌŚŽŽŐĚĞ &'ͲŽƉŶĂŵĞ ŝŶ ŚĞƚ ďĞĞŶŵĞƌŐ ĂĂŶ ŝŶ ƉĂƟģŶƚĞŶ ŵĞƚ ŚŽŽŐ ƌĞŵŶĂŶƚ ĐŚŽůĞƐƚĞƌŽů ĞŶ Ěŝƚ ĐŽƌƌĞůĞĞƌƚ ĂĂŶ ŚĞƚ ŚŽŐĞƌĞ ĂĂŶƚĂů ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ŝŶ ŚĞƚ ďůŽĞĚ͘ ŝƚ ƐƵŐŐĞƌĞĞƌƚ ĞĞŶ ĞīĞĐƚ ǀĂŶ ƌĞŵŶĂŶƚ ĐŚŽůĞƐƚĞƌŽů ŽƉ ĚĞ ĂĂŶŵĂĂŬ ǀĂŶ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ŝŶ ŚĞƚ ďĞĞŶŵĞƌŐ͘ Kŵ ĚĞnjĞ ŚLJƉŽƚŚĞƐĞ ƚĞ ŽŶĚĞƌƐƚĞƵŶĞŶ ŚĞďďĞŶǁĞŝŶŚĞƚůĂďŽƌĂƚŽƌŝƵŵĂĂŶŐĞƚŽŽŶĚĚĂƚƌĞŵŶĂŶƚĐŚŽůĞƐƚĞƌŽůŬĂŶŽƉŚŽƉĞŶŝŶ,^WƐ͕ ĚŝƚnjŽƌŐƚĞƌǀŽŽƌĚĂƚĚĞƐƚĂŵĐĞůůĞŶnjŝĐŚŵĞĞƌŽŶƚǁŝŬŬĞůĞŶƌŝĐŚƟŶŐŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ͘ŝƚŝƐ onderbouwd door een verband aan te tonen tussen remnant cholesterol en de hoeveelheid ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŝŶŚĞƚďůŽĞĚŝŶĚĞŽƉĞŶŚĂŐĞŶ'ĞŶĞƌĂůWŽƉƵůĂƟŽŶ^ƚƵĚLJ͘^ĂŵĞŶǀĂƩĞŶĚ͗ ƌĞŵŶĂŶƚĐŚŽůĞƐƚĞƌŽůŬĂŶnjŽǁĞůŽŶƚƐƚĞŬŝŶŐŝŶĚĞǀĂĂƚǁĂŶĚĂůƐĂĐƟǀĂƟĞǀĂŶŚĞƚďĞĞŶŵĞƌŐ ǀĞƌŽŽƌnjĂŬĞŶ͕ǁĂƚůĞŝĚƚƚŽƚŵĞĞƌĞŶĂĐƟĞǀĞƌĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŝŶŚĞƚďůŽĞĚ͘

ĞŶ ĂŶĚĞƌĞ ĨĂĐƚŽƌ ĚŝĞ ŬĂŶ ďŝũĚƌĂŐĞŶ ĂĂŶ ĂƚŚĞƌŽƐĐůĞƌŽƐĞ ŝƐ ŚĞƚ ǀĞƚĚĞĞůƚũĞ ůŝƉŽƉƌŽƚĞŝŶĞ ;ĂͿ ;>Ɖ;ĂͿ͘ŝƚŝƐĞĞŶĚĞĞůƚũĞĚĂƚůŝũŬƚŽƉ>>ĐŚŽůĞƐƚĞƌŽů͕ŵĂĂƌĚĂŶŵĞƚĞĞŶĂƉŽ;ĂͿĞŝǁŝƚͲƐƚĂĂƌƚ͘

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EĞĚĞƌůĂŶĚƐĞƐĂŵĞŶǀĂƫŶŐ

,ĞƚŝƐďĞŬĞŶĚĚĂƚĞĞŶǀĞƌŚŽŽŐĚ>Ɖ;ĂͿŬĂŶůĞŝĚĞŶƚŽƚŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶĞŶĚĂƚƉĂƟģŶƚĞŶŵĞƚ ƉƌĞŵĂƚƵƌĞĂƚŚĞƌŽƐĐůĞƌŽƐĞ;ƉĂƟģŶƚĞŶĚŝĞŽƉũŽŶŐĞůĞĞŌŝũĚĂůŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶŚĞďďĞŶͿ ǀĂŬĞƌĞĞŶŚŽŽŐ>Ɖ;ĂͿŚĞďďĞŶ͘&ĂŵŝůŝĞůĞĚĞŶǀĂŶƉĂƟģŶƚĞŶŵĞƚƉƌĞŵĂƚƵƌĞĂƚŚĞƌŽƐĐůĞƌŽƐĞ hebben zelf ook meer kans op het krijgen van hart- en vaatziekten en zij hebben dan ook vaak ƉůĂƋƵĞƐŝŶĞĞŶŵĞĞƌŐĞǀŽƌĚĞƌĚnjŝĞŬƚĞƐƚĂĚŝƵŵĚĂŶůĞĞŌŝũĚƐŐĞŶŽƚĞŶnjŽŶĚĞƌĨĂŵŝůŝĞůĞĚĞŶŵĞƚ ƉƌĞŵĂƚƵƌĞ ĂƚŚĞƌŽƐĐůĞƌŽƐĞ͘ ,ŽĞ >Ɖ;ĂͿ ŚĂƌƚͲ ĞŶ ǀĂĂƚnjŝĞŬƚĞŶ ŬĂŶ ǀĞƌŽŽƌnjĂŬĞŶ ŝƐ ŵĂĂƌ ĚĞĞůƐ ďĞŬĞŶĚ͘,ĞƚŝƐďĞŬĞŶĚĚĂƚ>Ɖ;ĂͿĞĞŶŽŶƚƐƚĞŬŝŶŐƐƌĞĂĐƟĞƚĞǁĞĞŐŬĂŶďƌĞŶŐĞŶ͕ŵĂĂƌŵŽŐĞůŝũŬ njŽƌŐƚŚĞƚŽŽŬĚŝƌĞĐƚǀŽŽƌĚĞǀĞƌŬĂůŬŝŶŐǀĂŶƉůĂƋƵĞƐ͘ĂĂƌŽŵŚĞďďĞŶǁĞŐĞŬĞŬĞŶŶĂĂƌĚĞ ƌĞůĂƟĞƚƵƐƐĞŶ>Ɖ;ĂͿĞŶĐĂůĐŝƵŵƐĐŽƌĞ͕ĞĞŶŵĂĂƚǀŽŽƌĚĞǀĞƌŬĂůŬŝŶŐǀĂŶƉůĂƋƵĞƐ͕ŝŶƉĞƌƐŽŶĞŶ met familieleden met premature atherosclerose. In ŚŽŽĨĚƐƚƵŬϳ laten we zien dat verhoogd

>Ɖ;ĂͿŝƐŐĞĂƐƐŽĐŝĞĞƌĚŵĞƚĞĞŶŚŽŐĞƌĞĐĂůĐŝƵŵƐĐŽƌĞ͘ĞnjĞĚĂƚĂƚŽŶĞŶĚƵƐĂĂŶĚĂƚǀĞƌŚŽŽŐĚ >Ɖ;ĂͿĚĞƉƌŽŐƌĞƐƐŝĞǀĂŶĚĞŽŶƚǁŝŬŬĞůŝŶŐǀĂŶĂƚŚĞƌŽƐĐůĞƌŽƐĞŬĂŶǀĞƌƐŶĞůůĞŶŝŶƉĞƌƐŽŶĞŶŵĞƚ ĨĂŵŝůŝĞůĞĚĞŶŵĞƚƉƌĞŵĂƚƵƌĞĂƚŚĞƌŽƐĐůĞƌŽƐĞ͘,ĞƚŝƐĚĂŶŽŽŬďĞůĂŶŐƌŝũŬŽŵŚĞƚ>Ɖ;ĂͿŝŶĚĞnjĞ personen te meten. EŝĞƚĂůůĞĞŶǀĞƚƌŝũŬĞĚĞĞůƚũĞƐŬƵŶŶĞŶĂƚŚĞƌŽƐĐůĞƌŽƐĞǀĞƌŽŽƌnjĂŬĞŶ͘KŽŬĂŶĚĞƌĞnjŝĞŬƚĞŶŬƵŶŶĞŶ ůĞŝĚĞŶƚŽƚĞĞŶŚŽŐĞƌƌŝƐŝĐŽŽƉŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶ͘ŝũǀŽŽƌďĞĞůĚƉĂƟģŶƚĞŶŵĞƚĐŚƌŽŶŝƐĐŚĞ ŶŝĞƌŝŶƐƵĸĐŝģŶƟĞ ;ƉĂƟģŶƚĞŶ ŵĞƚ ĞĞŶ ǀĞƌŵŝŶĚĞƌĚĞ ŶŝĞƌĨƵŶĐƟĞͿ ŚĞďďĞŶ ĞĞŶ ŚŽŐĞƌ ƌŝƐŝĐŽ op hart- en vaatziekten. Aangezien het ontstekingsproces belangrijk is in de ontwikkeling ǀĂŶ ĂƚŚĞƌŽƐĐůĞƌŽƐĞ͕ ŚĞďďĞŶ ǁĞ ŽŶĚĞƌnjŽĐŚƚ ŽĨ ĚĂƚ ŽŽŬ ĞĞŶ ƌŽů ƐƉĞĞůƚ ŝŶ ĚĞ ŽŶƚǁŝŬŬĞůŝŶŐ ǀĂŶ ĂƚŚĞƌŽƐĐůĞƌŽƐĞ ŝŶ ƉĂƟģŶƚĞŶ ŵĞƚ ĞĞŶ ĐŚƌŽŶŝƐĐŚĞ ŶŝĞƌŝŶƐƵĸĐŝģŶƟĞ͘ /Ŷ ŚŽŽĨĚƐƚƵŬ ϴ ďĞƐĐŚƌŝũǀĞŶ ǁĞ ĞĞŶ ǀĞƌŚŽŽŐĚĞ ŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ ǀĂŶ ƉĂƟģŶƚĞŶ ŵĞƚ ĐŚƌŽŶŝƐĐŚĞŶŝĞƌŝŶƐƵĸĐŝģŶƟĞ͘ĂĂƌŶĂĂƐƚůĂƚĞŶǁĞnjŝĞŶĚĂƚĚĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŝŶŚĞƚďůŽĞĚ ĂĐƟĞǀĞƌ njŝũŶ ĞŶ ŵĂŬŬĞůŝũŬĞƌ ĚĞ ǀĂĂƚǁĂŶĚ ŝŶ ŬƵŶŶĞŶ ďĞǁĞŐĞŶ͘ tĞ ƚŽŶĞŶ ǀĞƌĚĞƌ ĂĂŶ ĚĂƚ Ğƌ ŵĞĞƌĚĞƌĞ ĨĂĐƚŽƌĞŶ njŝũŶ ĚŝĞ ĞĞŶ ƌŽů ƐƉĞůĞŶ ŝŶ ĚĞ ŚŽŐĞƌĞ ŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚ ďŝũ ĚĞnjĞ ƉĂƟģŶƚĞŶ͘ĞǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐǁŽƌĚƚďĞŢŶǀůŽĞĚƚĚŽŽƌĚĞƐůĞĐŚƚĞƌĞŶŝĞƌĨƵŶĐƟĞ͕ĚŽŽƌĞĞŶ ǀĞƌŚŽŽŐĚƵƌĞƵŵŝŶŚĞƚďůŽĞĚ;ĚŝƚŝƐŚĞƚĂĩƌĂĂŬƉƌŽĚƵĐƚǀĂŶĞŝǁŝƩĞŶĚĂƚŶƵŵŝŶĚĞƌŐŽĞĚ ǁŽƌĚƚƵŝƚŐĞƐĐŚĞŝĚĞŶĚŽŽƌĚĞŶŝĞƌĞŶͿĞŶĚŽŽƌĚĞďůŽĞĚĚƌƵŬ͘/ŶĚŝƚŚŽŽĨĚƐƚƵŬůĂƚĞŶǁĞĚƵƐ njŝĞŶĚĂƚŚĞƚŶŝĞƚĂůůĞĞŶǀĞƚƌŝũŬĞĚĞĞůƚũĞƐnjŝũŶĚŝĞĞĞŶŽŶƚƐƚĞŬŝŶŐƐƌĞĂĐƟĞŬƵŶŶĞŶǀĞƌŽŽƌnjĂŬĞŶ ĚŝĞ ůĞŝĚƚ ƚŽƚ ĂƚŚĞƌŽƐĐůĞƌŽƐĞ͕ ŵĂĂƌ ĚĂƚ ƉĂƟģŶƚĞŶ ŵĞƚ ĐŚƌŽŶŝƐĐŚĞ ŶŝĞƌŝŶƐƵĸĐŝģŶƟĞ ŽŽŬ ŵĞĞƌ ǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ ĞŶ ĂĐƟĞǀĞƌĞ ŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶ ŝŶ ŚĞƚ ďůŽĞĚ ŚĞďďĞŶ͘ EŝĞƚ ĂůůĞĞŶ ƉĂƟģŶƚĞŶ ŵĞƚ ĐŚƌŽŶŝƐĐŚĞ ŶŝĞƌŝŶƐƵĸĐŝģŶƟĞ ŚĞďďĞŶ ŵĞĞƌ ƌŝƐŝĐŽ ŽƉ ŚĂƌƚͲ ĞŶ ǀĂĂƚnjŝĞŬƚĞŶ͕ ŵĂĂƌ ŽŽŬ ƉĂƟģŶƚĞŶ ŵĞƚ ĐŚƌŽŶŝƐĐŚĞ ŽŶƚƐƚĞŬŝŶŐƐnjŝĞŬƚĞŶ ŚĞďďĞŶ ĞĞŶ ŚŽŐĞƌ ƌŝƐŝĐŽ͘ ĞŶ ǀŽŽƌďĞĞůĚ ŝƐ ƉĂƟģŶƚĞŶ ŵĞƚ ƉĞƌŝĨĞƌĞ ƐƉŽŶĚLJůĂƌƚƌŝƟƐ͕ ĞĞŶ njŝĞŬƚĞ ĚŝĞ ŐĞƉĂĂƌĚ ŐĂĂƚ ŵĞƚ ŽŶƚƐƚĞŬŝŶŐĞŶ ŝŶ ĚĞ ŐĞǁƌŝĐŚƚĞŶ͘ ƌ ŝƐ Ăů ĞĞƌĚĞƌ ĂĂŶŐĞƚŽŽŶĚ ĚĂƚ ĚĞnjĞ ƉĂƟģŶƚĞŶ ŵĞĞƌ ŽŶƚƐƚĞŬŝŶŐ ŝŶ ĚĞ ǀĂĂƚǁĂŶĚ ŚĞďďĞŶ͘ ZĞĐĞŶƚ ŝƐ Ğƌ ĞĞŶ ŶŝĞƵǁ ŵĞĚŝĐŝũŶ ŽƉ ĚĞ ŵĂƌŬƚ ŐĞŬŽŵĞŶ ǀŽŽƌ ƉĂƟģŶƚĞŶ ŵĞƚ ƐƉŽŶĚLJůĂƌƚƌŝƟƐ͕ ŶĂŵĞůŝũŬ ƐĞĐƵŬŝŶƵŵĂď͕ ĞĞŶ />ϭϳ ƌĞŵŵĞƌ͘ />ϭϳ ŝƐ ĞĞŶ ĐLJƚŽŬŝŶĞ͕ ŽŶĚĞƌĚĞĞů ǀĂŶ ŚĞƚ ŝŵŵƵƵŶƐLJƐƚĞĞŵ͕ĚĂƚ ĞĞŶ ďĞůĂŶŐƌŝũŬĞ ƌŽů ƐƉĞĞůƚ

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ŝŶ ĚĞ njŝĞŬƚĞĂĐƟǀŝƚĞŝƚ ǀĂŶ ƐƉŽŶĚLJůĂƌƚƌŝƟƐ͘ KĨ />ϭϳ ŽŽŬ ĞĞŶ ƌŽů ƐƉĞĞůƚ ŝŶ ĚĞ ŽŶƚǁŝŬŬĞůŝŶŐ ǀĂŶ ǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ ŝŶ ƉĂƟĞŶƚĞŶ ŵĞƚ ƐƉŽŶĚLJůĂƌƚƌŝƟƐ ŝƐ ŶŝĞƚ ĚƵŝĚĞůŝũŬ͘ ĂĂƌŽŵ beschrijven we in ŚŽŽĨĚƐƚƵŬϵŚĞƚĞīĞĐƚǀĂŶƚǁĂĂůĨǁĞŬĞŶďĞŚĂŶĚĞůŝŶŐŵĞƚƐĞĐƵŬŝŶƵŵĂď ŽƉǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐŝŶƉĂƟģŶƚĞŶŵĞƚƉĞƌŝĨĞƌĞƐƉŽŶĚLJůĂƌƚƌŝƟƐ͘tĞůĂƚĞŶnjŝĞŶĚĂƚƚǁĂĂůĨ ǁĞŬĞŶ ďĞŚĂŶĚĞůŝŶŐ ĞĞŶ ǀĞƌůĂŐŝŶŐ ǀĂŶ ĚĞ ǀĂĂƚǁĂŶĚŽŶƚƐƚĞŬŝŶŐ ƚĞǁĞĞŐ ďƌĞŶŐƚ͕ ĞŶ ĚĂŶ ǀŽŽƌĂůŝŶƉĂƟģŶƚĞŶĚŝĞŐŽĞĚƌĞĂŐĞƌĞŶŽƉĚĞŵĞĚŝĐĂƟĞ͘ŝƚŝƐĞĞŶĂĂŶǁŝũnjŝŶŐĚĂƚŶŝĞƚĂůůĞĞŶ ŵĞĚŝĐŝũŶĞŶĚŝĞĐŚŽůĞƐƚĞƌŽůǀĞƌůĂŐĞŶ͕ŵĂĂƌŽŽŬŵĞĚŝĐŝũŶĞŶĚŝĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚǀĞƌůĂŐĞŶ ŬƵŶŶĞŶnjŽƌŐĞŶǀŽŽƌĞĞŶǀĞƌŵŝŶĚĞƌŝŶŐǀĂŶĚĞŽŶƚƐƚĞŬŝŶŐƐĂĐƟǀŝƚĞŝƚŝŶĚĞǀĂĂƚǁĂŶĚ͘ ŽŶĐůƵĚĞƌĞŶĚ͕ŶŝĞƚĂůůĞĞŶĚĞǀĂĂƚǁĂŶĚ͕ŵĂĂƌŽŽŬĚĞŽŶƚƐƚĞŬŝŶŐƐĐĞůůĞŶŝŶŚĞƚďůŽĞĚĞŶŚĞƚ ďĞĞŶŵĞƌŐĞŶĚĞŵŝůƚnjŝũŶďĞƚƌŽŬŬĞŶďŝũĚĞŽŶƚƐƚĞŬŝŶŐƐƌĞĂĐƟĞĚŝĞƌĞƐƵůƚĞĞƌƚŝŶĂƚŚĞƌŽƐĐůĞƌŽƐĞ͘ KŶƚƐƚĞŬŝŶŐƐƌĞŵŵĞŶĚĞŵĞĚŝĐŝũŶĞŶĚŝĞŚŝĞƌŽƉŝŶŐƌŝũƉĞŶnjŝũŶĚĂŶŽŽŬǀĞĞůďĞůŽǀĞŶĚĂůƐŶŝĞƵǁĞ behandeling voor hart- en vaatziekten.

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ƵƚŚŽƌƐĂŶĚĂĸůŝĂƟŽŶƐ

hd,KZ^E&&/>/d/KE^

ŽŵŝŶŝƋƵĞ>͘W͘ĂĞƚĞŶ ŵƐƚĞƌĚĂŵZŚĞƵŵĂƚŽůŽŐLJĂŶĚ/ŵŵƵŶŽůŽŐLJĞŶƚĞƌ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕ŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ ^ŝƌŽŽŶĞŬŬĞƌŝŶŐ ĞƉĂƌƚŵĞŶƚŽĨdžƉĞƌŝŵĞŶƚĂů/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞ͕ZĂĚďŽƵĚhŶŝǀĞƌƐŝƚLJDĞĚŝĐĂůĞŶƚĞƌ͕EŝũŵĞŐĞŶ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ ĞƉĂƌƚŵĞŶƚŽĨdžƉĞƌŝŵĞŶƚĂůsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ dŚĞEĞƚŚĞƌůĂŶĚƐ ^ŽƉŚŝĞ:͘ĞƌŶĞůŽƚDŽĞŶƐ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ^͘DĂƩŚŝũƐŽĞŬŚŽůĚƚ ĞƉĂƌƚŵĞŶƚŽĨĂƌĚŝŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ DĞƌŝũŶŽƐ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands :ƵůŝĂŶ͘ǀĂŶĂƉĞůůĞǀĞĞŶ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ZŽŶĂŬĞůĞǁŝ ĞƉĂƌƚŵĞŶƚŽĨĂƌĚŝŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ ZĂƉŚĂĞůǀĂŶƵŝǀĞŶǀŽŽƌĚĞŶ ĞƉĂƌƚŵĞŶƚŽĨEĞƉŚƌŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ zĂŶŶŝĐŬ<ĂŝƐĞƌ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands :ĞīƌĞLJ<ƌŽŽŶ ĞƉĂƌƚŵĞŶƚŽĨdžƉĞƌŝŵĞŶƚĂůsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ dŚĞEĞƚŚĞƌůĂŶĚƐ ĂƌůŝũŶ<ƵŝũŬ ĞƉĂƌƚŵĞŶƚŽĨ,ĞŵĂƚŽƉŽŝĞƐŝƐ͕^ĂŶƋƵŝŶZĞƐĞĂƌĐŚ͕ĂŶĚ>ĂŶĚƐƚĞŝŶĞƌ>ĂďŽƌĂƚŽƌLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚƌĞ͕ hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ

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ŶŶĞ>ĂŶŐƐƚĞĚ dŚĞŽƉĞŶŚĂŐĞŶ'ĞŶĞƌĂůWŽƉƵůĂƟŽŶƐƚƵĚLJĂŶĚĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂůŝŽĐŚĞŵŝƐƚƌLJ͕,ĞƌůĞǀĂŶĚ'ĞŶƚŽŌĞ ,ŽƐƉŝƚĂů͕ŽƉĞŶŚĂŐĞŶhŶŝǀĞƌƐŝƚLJ,ŽƐƉŝƚĂů͕ĞŶŵĂƌŬ ,ĞŶŬ͘DĂƌƋƵĞƌŝŶŐ ĞƉĂƌƚŵĞŶƚŽĨZĂĚŝŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ͖ ĞƉĂƌƚŵĞŶƚŽĨŝŽŵĞĚŝĐĂůŶŐŝŶĞĞƌŝŶŐĂŶĚWŚLJƐŝĐƐ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ >ĞŽŶŝĞŬĞ:͘:͘ǀĂŶDĞŶƐ ŵƐƚĞƌĚĂŵZŚĞƵŵĂƚŽůŽŐLJĂŶĚ/ŵŵƵŶŽůŽŐLJĞŶƚĞƌ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕ŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ DĂƩŚŝĂƐEĂŚƌĞŶĚŽƌĨ ĞŶƚĞƌĨŽƌ^LJƐƚĞŵƐŝŽůŽŐLJ͕DĂƐƐĂĐŚƵƐĞƩƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂůĂŶĚ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽů͕ŽƐƚŽŶ͕h^ Ăƌƚ:͘EĞĚĞƌǀĞĞŶ ĞƉĂƌƚŵĞŶƚŽĨZĂĚŝŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ ƆƌŐĞ'͘EŽƌĚĞƐƚŐĂĂƌĚ dŚĞŽƉĞŶŚĂŐĞŶ'ĞŶĞƌĂůWŽƉƵůĂƟŽŶƐƚƵĚLJĂŶĚĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂůŝŽĐŚĞŵŝƐƚƌLJ͕,ĞƌůĞǀĂŶĚ'ĞŶƚŽŌĞ ,ŽƐƉŝƚĂů͕ŽƉĞŶŚĂŐĞŶhŶŝǀĞƌƐŝƚLJ,ŽƐƉŝƚĂů͕ĞŶŵĂƌŬ EŝĐŬ^͘EƵƌŵŽŚĂŵĞĚ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands :ĂŶ:͘WŝĞŬ ĞƉĂƌƚŵĞŶƚŽĨĂƌĚŝŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ^ĂƌĂͲ:ŽĂŶWŝŶƚŽͲ^ŝĞƚƐŵĂ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ ĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂůƉŝĚĞŵŝŽůŽŐLJ͕ŝŽƐƚĂƟƐƟĐƐĂŶĚŝŽŝŶĨŽƌŵĂƟĐƐ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨ ŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ Z͘EŝůƐWůĂŶŬĞŶ ĞƉĂƌƚŵĞŶƚŽĨZĂĚŝŽůŽŐLJĂŶĚEƵĐůĞĂƌDĞĚŝĐŝŶĞ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ DĂƵƌŝĐĞt͘:͘ĚĞZŽŶĚĞ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ ĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂůƉŝĚĞŵŝŽůŽŐLJ͕ŝŽƐƚĂƟƐƟĐƐĂŶĚŝŽŝŶĨŽƌŵĂƟĐƐ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨ ŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ

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ƵƚŚŽƌƐĂŶĚĂĸůŝĂƟŽŶƐ :ĂŵĞƐ,͘&͘ZƵĚĚ ŝǀŝƐŝŽŶŽĨĂƌĚŝŽǀĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕hŶŝǀĞƌƐŝƚLJŽĨĂŵďƌŝĚŐĞ͕ĂŵďƌŝĚŐĞ͕hŶŝƚĞĚ<ŝŶŐĚŽŵ :ŽŚĂŶ͘'͘^ĐŚŶŝƚnjůĞƌ ĞƉĂƌƚŵĞŶƚŽĨdžƉĞƌŝŵĞŶƚĂůsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ dŚĞEĞƚŚĞƌůĂŶĚƐ >ŽƩĞ͘͘^ƟĞŬĞŵĂ ĞƉĂƌƚŵĞŶƚ ŽĨ sĂƐĐƵůĂƌ DĞĚŝĐŝŶĞ͕ ĐĂĚĞŵŝĐ DĞĚŝĐĂů ĞŶƚĞƌ͕ hŶŝǀĞƌƐŝƚLJ ŽĨ ŵƐƚĞƌĚĂŵ͕ ŵƐƚĞƌĚĂŵ͕ dŚĞ Netherlands Ăƌƚ͘^ƚƌĂŶŐ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ŚĂƌůŽƩĞ/͘^ƚƌŽĞƐ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ƌŝŬ^͘'͘^ƚƌŽĞƐ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands &ůĞƵƌD͘ǀĂŶĚĞƌsĂůŬ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ZƵƚŐĞƌsĞƌďĞĞŬ ĞƉĂƌƚŵĞŶƚŽĨsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞ Netherlands ,ĞŝŶ:͘sĞƌďĞƌŶĞ ĞƉĂƌƚŵĞŶƚŽĨZĂĚŝŽůŽŐLJĂŶĚEƵĐůĞĂƌDĞĚŝĐŝŶĞ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ DŝƌĂŶĚĂsĞƌƐůŽŽƚ ĞƉĂƌƚŵĞŶƚŽĨdžƉĞƌŝŵĞŶƚĂůsĂƐĐƵůĂƌDĞĚŝĐŝŶĞ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕ dŚĞEĞƚŚĞƌůĂŶĚƐ ĂƌůŝũŶsŽĞƌŵĂŶƐ ĞƉĂƌƚŵĞŶƚŽĨ,ĞŵĂƚŽƉŽŝĞƐŝƐ͕^ĂŶƋƵŝŶZĞƐĞĂƌĐŚ͕ĂŶĚ>ĂŶĚƐƚĞŝŶĞƌ>ĂďŽƌĂƚŽƌLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚƌĞ͕ hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ >ŝīĞƌƚsŽŐƚ ĞƉĂƌƚŵĞŶƚŽĨEĞƉŚƌŽůŽŐLJ͕ĐĂĚĞŵŝĐDĞĚŝĐĂůĞŶƚĞƌ͕hŶŝǀĞƌƐŝƚLJŽĨŵƐƚĞƌĚĂŵ͕ŵƐƚĞƌĚĂŵ͕dŚĞEĞƚŚĞƌůĂŶĚƐ

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ϭ͘ WƌŽůŽŶŐĞĚ ŚĞŵĂƚŽƉŽŝĞƟĐ ĂŶĚ ŵLJĞůŽŝĚ ĐĞůůƵůĂƌ ƌĞƐƉŽŶƐĞ ŝŶ ƉĂƟĞŶƚƐ ĂŌĞƌ ĂŶ ĂĐƵƚĞ ĐŽƌŽŶĂƌLJ ƐLJŶĚƌŽŵĞ ŵĞĂƐƵƌĞĚ ǁŝƚŚ18&ͲWͲϳϭϰ Wdͬd͘ sĞƌǁĞŝũ ^>͖ ^ƟĞŬĞŵĂ >͖ ĞůĞǁŝ Z͕ ŚĞŶŐ <,͕ ĞƌŶĞůŽƚDŽĞŶƐ^:͖<ƌŽŽŶ:͖^ƚƌŽĞƐ/͖sĞƌƐůŽŽƚD͕WŝĞŬ::͕sĞƌďĞƌŶĞ,:͕^ƚƌŽĞƐ^'͘Ƶƌ:EƵĐůDĞĚDŽů /ŵĂŐŝŶŐϮϬϭϴ͘Ɖ͖ƵďĂŚĞĂĚŽĨƉƌŝŶƚ Ϯ͘ ĂƌĚŝŽǀĂƐĐƵůĂƌ ĚŝƐĞĂƐĞ ƌŝƐŬ ĂƐƐŽĐŝĂƚĞĚ ǁŝƚŚ ĞůĞǀĂƚĞĚ ůŝƉŽƉƌŽƚĞŝŶ;ĂͿ ĂƩĞŶƵĂƚĞƐ Ăƚ ůŽǁ ůŽǁͲĚĞŶƐŝƚLJ ůŝƉŽƉƌŽƚĞŝŶ ĐŚŽůĞƐƚĞƌŽů ůĞǀĞůƐ ŝŶ ƉƌŝŵĂƌLJ ƉƌĞǀĞŶƟŽŶ ƐĞƫŶŐ͘ sĞƌďĞĞŬ Z͕ ,ŽŽŐĞǀĞĞŶZD͕>ĂŶŐƐƚĞĚ͕^ƟĞŬĞŵĂ>͕sĞƌǁĞŝũ^>͕,ŽǀŝŶŐŚ'<͕tĂƌĞŚĂŵE:͕<ŚĂǁ<d͕ŽĞŬŚŽůĚƚ^D͕ EŽƌĚĞƐƚŐĂĂƌĚ'͕^ƚƌŽĞƐ^'͘Ƶƌ,ĞĂƌƚ:ϮϬϭϴƉƵďĂŚĞĂĚŽĨƉƌŝŶƚ͘ ϯ͘ ^ĞĐƵŬŝŶƵŵĂď ƚƌĞĂƚŵĞŶƚ ĚĞĐƌĞĂƐĞƐ ĂƌƚĞƌŝĂů ǁĂůů ŝŶŇĂŵŵĂƟŽŶ ŝŶ ƉĂƟĞŶƚƐ ǁŝƚŚ ƉĞƌŝƉŚĞƌĂů ƐƉŽŶĚLJůŽĂƌƚŚƌŝƟƐ͘sĞƌǁĞŝũ^>͖ǀĂŶDĞŶƐ>::͖ĞƌŶĞůŽƚDŽĞŶƐ^:͖sĞƌďĞƌŶĞ,:͖^ƚƌŽĞƐ^'͖ĂĞƚĞŶ>W͘ ^ƵďŵŝƩĞĚ ϰ͘ůĞǀĂƚĞĚ>ŝƉŽƉƌŽƚĞŝŶ;ĂͿůĞǀĞůƐĂƌĞĂƐƐŽĐŝĂƚĞĚǁŝƚŚĐŽƌŽŶĂƌLJĂƌƚĞƌLJĐĂůĐŝƵŵƐĐŽƌĞƐŝŶĂƐLJŵƉƚŽŵĂƟĐ ŝŶĚŝǀŝĚƵĂůƐ ǁŝƚŚ Ă ĨĂŵŝůLJ ŚŝƐƚŽƌLJ ŽĨ ƉƌĞŵĂƚƵƌĞ ĂƚŚĞƌŽƐĐůĞƌŽƟĐ ĐĂƌĚŝŽǀĂƐĐƵůĂƌ ĚŝƐĞĂƐĞ͘ sĞƌǁĞŝũ ^>͕ ĚĞ ZŽŶĚĞ Dt:͕ sĞƌďĞĞŬ Z͕ ŽĞŬŚŽůĚƚ ^D͕ WůĂŶŬĞŶ ZE͕ ^ƚƌŽĞƐ ^'͕ WŝŶƚŽͲ^ŝĞƚƐŵĂ ^͘ :ůŝŶ>ŝƉŝĚŽů͕ϮϬϭϴ. ƉƵďĞŚĞĂĚŽĨƉƌŝŶƚ. ϱ͘ZϮĞdžƉƌĞƐƐŝŽŶŽŶĐŝƌĐƵůĂƟŶŐŵŽŶŽĐLJƚĞƐŝƐĂƐƐŽĐŝĂƚĞĚǁŝƚŚĂƌƚĞƌŝĂůǁĂůůŝŶŇĂŵŵĂƟŽŶĂƐƐĞƐƐĞĚ ďLJ18&Ͳ&' Wdͬd ŝŶ ƉĂƟĞŶƚƐ Ăƚ ƌŝƐŬ ĨŽƌ  ĐĂƌĚŝŽǀĂƐĐƵůĂƌ ĚŝƐĞĂƐĞ͘ sĞƌǁĞŝũ ^>͕ ƵŝǀĞŶǀŽŽƌĚĞŶ Z͕ ^ƟĞŬĞŵĂ>͕EƵƌŵŽŚĂŵĞĚE^͕ǀĂŶĚĞƌsĂůŬ&D͕sĞƌƐůŽŽƚD͕sĞƌďĞƌŶĞ,:͕^ƚƌŽĞƐ^'͕EĂŚƌĞŶĚŽƌĨD͕ ĞŬŬĞƌŝŶŐ^͕ĞƌŶĞůŽƚDŽĞŶƐ^:͘ĂƌĚŝŽǀĂƐĐZĞƐ͘ϮϬϭϳ͖ϭϭϰ;ϯͿ͗ϰϲϴͲϰϳϱ ϲ͘ ZĞŵŶĂŶƚ ĐŚŽůĞƐƚĞƌŽů ĞůŝĐŝƚƐ ĂƌƚĞƌŝĂů ǁĂůů ŝŶŇĂŵŵĂƟŽŶ ĂŶĚ Ă ŵƵůƟůĞǀĞů ĐĞůůƵůĂƌ ŝŵŵƵŶĞ response in humans. sĞƌǁĞŝũ ^>͕ ĞƌŶĞůŽƚ DŽĞŶƐ ^:͕ ^ĐŚŶŝƚnjůĞƌ :'͕ ^ƟĞŬĞŵĂ >͕ ŽƐ D͕ >ĂŶŐƐƚĞĚ ͕ <ƵŝũŬ ͕ ĞŬŬĞƌŝŶŐ ^͕ sŽĞƌŵĂŶƐ ͕ sĞƌďĞƌŶĞ ,:͕ EŽƌĚĞƐƚŐĂĂƌĚ '͕ ^ƚƌŽĞƐ ^'͕ <ƌŽŽŶ :͘ ƌƚĞƌŝŽƐĐůĞƌdŚƌŽŵďsĂƐĐŝŽů͘ϮϬϭϳ͖ϯϳ;ϱͿ͗ϵϲϵͲϵϳϱ

ϳ͘ƌƚĞƌŝĂůĂŶĚĐĞůůƵůĂƌŝŶŇĂŵŵĂƟŽŶŝŶƉĂƟĞŶƚƐǁŝƚŚ<͘ĞƌŶĞůŽƚDŽĞŶƐ^:͕sĞƌǁĞŝũ^>͕van der Valk &D͕ǀĂŶĂƉĞůůĞǀĞĞŶ:͕<ƌŽŽŶ:͕sĞƌƐůŽŽƚD͕sĞƌďĞƌŶĞ,:͕DĂƌƋƵĞƌŝŶŐ,͕ƵŝǀĞŶǀŽŽƌĚĞŶZ͕sŽŐƚ>͕ ^ƚƌŽĞƐ^͘:ŵ^ŽĐEĞƉŚƌŽů͘ϮϬϭϳ͖Ϯϴ;ϰͿ͗ϭϮϳϴͲϭϮϴϱ͘ ϴ͘ /ŶĐƌĞĂƐĞĚ ŚĂĞŵĂƚŽƉŽŝĞƟĐ ĂĐƟǀŝƚLJ ŝŶ ƉĂƟĞŶƚƐ ǁŝƚŚ ĂƚŚĞƌŽƐĐůĞƌŽƐŝƐ͘ ǀĂŶ ĚĞƌ sĂůŬ &D͕ <ƵŝũŬ ͕ sĞƌǁĞŝũ ^>͕ ^ƟĞŬĞŵĂ >͕ <ĂŝƐĞƌ z͕ ĞĞƌůĞĚĞƌ ^͕ EĂŚƌĞŶĚŽƌĨ D͕ sŽĞƌŵĂŶƐ ͕ ^ƚƌŽĞƐ ^'͘ Ƶƌ,ĞĂƌƚ:͘ϮϬϭϳ͖ϯϴ;ϲͿ͗ϰϮϱͲϰϯϮ ϵ͘ĂƌŽƟĚĂƌƚĞƌŝĂůǁĂůůŝŶŇĂŵŵĂƟŽŶŝŶƉĞƌŝƉŚĞƌĂůĂƌƚĞƌLJĚŝƐĞĂƐĞŝƐĂƵŐŵĞŶƚĞĚďLJƚLJƉĞϮĚŝĂďĞƚĞƐ͗ Ă ĐƌŽƐƐͲƐĞĐƟŽŶĂů ƐƚƵĚLJ͘ ĞƌŶĞůŽƚ DŽĞŶƐ ^:͕ ^ƚŽĞŬĞŶďƌŽĞŬ ZD͕ ǀĂŶ ĚĞƌ sĂůŬ &D͕ sĞƌǁĞŝũ ^>͕ <ŽĞůĞŵĂLJD:͕sĞƌďĞƌŶĞ,:͕EŝĞƵǁĚŽƌƉD͕^ƚƌŽĞƐ^͘DĂƌĚŝŽǀĂƐĐŝƐŽƌĚ͘ϮϬϭϲ͖ϭϲ;ϭͿ͗Ϯϯϳ͘

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ϭϬ͘ dŚƌĞƐŚŽůĚƐ ĨŽƌ ĂƌƚĞƌŝĂů ǁĂůů ŝŶŇĂŵŵĂƟŽŶ ƋƵĂŶƟĮĞĚ ďLJ18&Ͳ&' Wd ŝŵĂŐŝŶŐ͗ ŝŵƉůŝĐĂƟŽŶƐ ĨŽƌ ǀĂƐĐƵůĂƌ ŝŶƚĞƌǀĞŶƟŽŶĂů ƐƚƵĚŝĞƐ͘ ǀĂŶ ĚĞƌ sĂůŬ &D͕ sĞƌǁĞŝũ ^>͕ ǁŝŶĚĞƌŵĂŶ <͕ ^ƚƌĂŶŐ ͕ <ĂŝƐĞƌ z͕ DĂƌƋƵĞƌŝŶŐ ,͕ EĞĚĞƌǀĞĞŶ :͕ ^ƚƌŽĞƐ ^͕ sĞƌďĞƌŶĞ ,:͕ ZƵĚĚ :,͘ : ĂƌĚŝŽǀĂƐĐ /ŵĂŐŝŶŐ͘ ϮϬϭϲ͖ϵ;ϭϬͿ͗ϭϭϵϴͲϭϮϬϳ͘ ϭϭ͘/ŶĐƌĞĂƐĞĚĂƌƚĞƌŝĂůǁĂůůŝŶŇĂŵŵĂƟŽŶŝŶƉĂƟĞŶƚƐǁŝƚŚĂŶŬLJůŽƐŝŶŐƐƉŽŶĚLJůŝƟƐŝƐƌĞĚƵĐĞĚďLJƐƚĂƟŶ ƚŚĞƌĂƉLJ͘ sĂŶ ĚĞƌ sĂůŬ &D͕ ĞƌŶĞůŽƚ DŽĞŶƐ ^:͕ sĞƌǁĞŝũ ^>͕ ^ƚƌĂŶĐ ͕ EĞĚĞƌǀĞĞŶ :͕ sĞƌďĞƌŶĞ ,:͕ EƵƌŵŽŚĂŵĞĚDd͕ĂĞƚĞŶ>͕^ƚƌŽĞƐ^͘ŶŶZŚĞƵŵŝƐ͘ϮϬϭϲ͖ϳϱ;ϭϬͿ͗ϭϴϰϴͲϱϭ ϭϮ͘ EŽǀĞů ĚŝƌĞĐƟŽŶƐ ŝŶ ŝŶŇĂŵŵĂƟŽŶ ĂƐ Ă ƚŚĞƌĂƉĞƵƟĐ ƚĂƌŐĞƚ ŝŶ ĂƚŚĞƌŽƐĐůĞƌŽƐŝƐ͘ sĞƌǁĞŝũ ^>͕ ǀĂŶĚĞƌǀĂůŬ&D͕^ƚƌŽĞƐ^͘ƵƌKƉŝŶ>ŝƉŝĚŽů͘ϮϬϭϱ͖Ϯϲ;ϲͿ͗ϱϴϬͲϱ

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About the author

ABOUT THE AUTHOR

^ŝŵŽŶĞsĞƌǁĞŝũǁĞƌĚŐĞďŽƌĞŶŽƉϭϵŵĂĂƌƚϭϵϴϴŝŶ,ŝůǀĞƌƐƵŵ͘/Ŷ<ŽƌƚĞŶŚŽĞĨǁŽŽŶĚĞnjĞ samen met haar ouders en 2 zussen. Na de middelbare school op het Comenius College ǁŝůĚĞnjĞŐƌĂĂŐŐĞŶĞĞƐŬƵŶĚĞƐƚƵĚĞƌĞŶ͘ŝƚŐŝŶŐŶŝĞƚnjŽŶĚĞƌƐůĂŐŽĨƐƚŽŽƚ͕ŶĂŽŵǁĞŐĞŶǀŝĂ de studies biologie in Utrecht en gezondheidswetenschappen aan de VU is ze uiteindelijk in ϮϬϬϴĚĂŶƚŽĐŚďĞŐŽŶŶĞŶŵĞƚĚĞŽƉůĞŝĚŝŶŐŐĞŶĞĞƐŬƵŶĚĞŝŶŚĞƚD͕ǁĂĂƌĞĞŶǀĞƌŚƵŝnjŝŶŐ ŶĂĂƌŵƐƚĞƌĚĂŵŶĂƚƵƵƌůŝũŬďŝũŚŽŽƌĚĞ͘EĂĞĞŶůĂĂƚƐƚĞŬĞƵnjĞĐŽƐĐŚĂƉŝŶ^ƵƌŝŶĂŵĞŚĞĞŌnjĞŝŶ ϮϬϭϰŚĂĂƌĂƌƚƐĞŶĚŝƉůŽŵĂŐĞŬƌĞŐĞŶ͘ĂĂƌŶĂŝƐnjĞďĞŐŽŶŶĞŶĂůƐƉƌŽŵŽǀĞŶĚƵƐŽƉĚĞĂĨĚĞůŝŶŐ ǀĂƐĐƵůĂŝƌĞŐĞŶĞĞƐŬƵŶĚĞŽŶĚĞƌƐƵƉĞƌǀŝƐŝĞǀĂŶƉƌŽĨ͘Ěƌ͘^ƚƌŽĞƐ͘,ĂĂƌŽŶĚĞƌnjŽĞŬŐŝŶŐŽǀĞƌĚĞ ƌŽůǀĂŶŝŶŇĂŵŵĂƟĞŝŶĂƚŚĞƌŽƐĐůĞƌŽƐĞĞŶĚĂŶƐƉĞĐŝĮĞŬĚĞďĞĞůĚǀŽƌŵŝŶŐŚŝĞƌǀĂŶŵĞƚWdͬd͘ ĂƚŚĞĞŌƵŝƚĞŝŶĚĞůŝũŬŐĞƌĞƐƵůƚĞĞƌĚŝŶĚŝƚƉƌŽĞĨƐĐŚƌŝŌ͘ KƉĚŝƚŵŽŵĞŶƚǁĞƌŬƚnjĞĂůƐE/K^ŝŶŚĞƚtĞƐƞƌŝĞƐŐĂƐƚŚƵŝƐďŝũĚĞŝŶƚĞƌŶĞŐĞŶĞĞƐŬƵŶĚĞĞŶ ǁŝůnjĞĚĂĂƌŶĂŐƌĂĂŐŚƵŝƐĂƌƚƐǁŽƌĚĞŶ͘ĞǁŽŽŶƚŝŶŵƐƚĞƌĚĂŵƐĂŵĞŶŵĞƚ:ƵůŝĂŶ͕ŽŶƚŵŽĞƚ op F4.

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E<tKKZ

ŶĚĂŶŶƵĚĞůĂĂƚƐƚĞǁŽŽƌĚĞŶǀĂŶĚŝƚƉƌŽĞĨƐĐŚƌŝŌ͘/ŬǁŝůŝĞĚĞƌĞĞŶĚŝĞŚĞĞŌďŝũŐĞĚƌĂŐĞŶĂĂŶ ĚŝƚƉƌŽĞĨƐĐŚƌŝŌŚĞĞůĞƌŐďĞĚĂŶŬĞŶ͘KŶĚĂŶŬƐĚĂƚŝŬŶŽŽŝƚŝĞĚĞƌĞĞŶŬĂŶďĞĚĂŶŬĞŶ͕ǁŝůŝŬƚŽĐŚ een poging wagen.

ůůĞƌĞĞƌƐƚǁŝůŝŬĚĞǀĞůĞƉĂƟĞŶƚĞŶĞŶŐĞnjŽŶĚĞǀƌŝũǁŝůůŝŐĞƌƐĚŝĞŚĞďďĞŶŵĞĞŐĞĚĂĂŶĂĂŶŵŝũŶ studies bedanken. ĞƐƚĞ ƌŝŬ͕ ƉƌŽŵŽƚŽƌ͕ ŚĞĞů ĞƌŐ ďĞĚĂŶŬƚ ǀŽŽƌ Ăů ũĞ ŚƵůƉ ĂĨŐĞůŽƉĞŶ ũĂƌĞŶ͘ :ƵŝƐƚ ƚŽĞŶ ŽŶnjĞ ǀĞƌƐĐŚŝůůĞŶ ŝŶ ǁĞƚĞŶƐĐŚĂƉƉĞůŝũŬĞ ĂŵďŝƟĞ ŶĂĂƌ ǀŽƌĞŶ ŬǁĂŵĞŶ͕ ƐƚŽŶĚ ũŝũ ŚŝĞƌǀŽŽƌ ŽƉĞŶ ĞŶ ƐƚŽŶĚũĞŬůĂĂƌǀŽŽƌĞĞŶĂůƚĞƌŶĂƟĞĨ͘,ŝĞƌĚŽŽƌŝƐŚĞƚǀŽŽƌŵŝũĞĞŶĮũŶĞǁĞƌŬŽŵŐĞǀŝŶŐŐĞďůĞǀĞŶ ǁĂĂƌŝŶŝŬŚĞƚďĞƐƚĞƵŝƚŵĞnjĞůĨŬŽŶŚĂůĞŶ͘:ŽƵǁƚŽŵĞůŽnjĞĂŵďŝƟĞĞŶĞŶƚŚŽƵƐŝĂƐŵĞĞŶŵŝũŶ ƉƌĂŐŵĂƟƐĐŚĞŶŽͲŶŽŶƐĞŶƐĂĂŶƉĂŬ;ŝŶũŽƵǁǁŽŽƌĚĞŶ͗ũŝũďĞŶƚĂůƟũĚǀĞĞůƚĞƌĞĂůŝƐƟƐĐŚͿŚĞĞŌ ƚŽƚĚŝƚƉƌŽĞĨƐĐŚƌŝŌŐĞůĞŝĚƚŵĞƚĞĞŶǀĞƌĚĞĚŝŐŝŶŐďŝŶŶĞŶϰũĂĂƌ͘ĞĚĂŶŬƚ͊ ĞƐƚĞ,ĞŝŶ͕ĐŽͲƉƌŽŵŽƚŽƌ͕ďĞĚĂŶŬƚǀŽŽƌũĞŝŶnjĞƚĚĞĂĨŐĞůŽƉĞŶũĂƌĞŶŽŵŵŝũƚĞŚĞůƉĞŶŵĞƚĂůůĞ ǀƌĂŐĞŶĞŶůŽŐŝƐƟĞŬƌŽŶĚŽŵĚĞƉĞƚƐĐĂŶƐ͕ĞĞŶďĞůĂŶŐƌŝũŬŽŶĚĞƌĚĞĞůǀĂŶŵŝũŶƉƌŽŵŽƟĞƚƌĂũĞĐƚ͘ >ŝĞǀĞ^ŽƉŚŝĞ͕ŝŶŚĞƚďĞŐŝŶĂůƐĐŽůůĞŐĂ͕ĂĂŶŚĞƚĞŝŶĚĞǁĂƐũĞĞĞŶŐƌŽƚĞƐƚĞƵŶĂůƐĐŽͲƉƌŽŵŽƚŽƌ͘ KƉŚĞƚƉƵŶƚĚĂƚŝŬŚĞƚŚĂƌĚƐƚĞďĞŐĞůĞŝĚŝŶŐŶŽĚŝŐŚĂĚǁĂƐũŝũĚĂĂƌĞŶǁŝůĚĞũĞŵĞŚŝĞƌďŝũ ŚĞůƉĞŶ͘,ĞĞůĞƌŐďĞĚĂŶŬƚǀŽŽƌĂůũŽƵǁƐƚĞƵŶĞŶĂĚǀŝĞnjĞŶĂĨŐĞůŽƉĞŶũĂƌĞŶ͘ 'ĞĂĐŚƚĞůĞĚĞŶǀĂŶĚĞƉƌŽŵŽƟĞĐŽŵŵŝƐƐŝĞ͕ŚĂƌƚĞůŝũŬĚĂŶŬǀŽŽƌŚĞƚůĞnjĞŶĞŶďĞŽŽƌĚĞůĞŶǀĂŶ ŵŝũŶƉƌŽĞĨƐĐŚƌŝŌĞŶĚĞďĞƌĞŝĚŚĞŝĚnjŝƫŶŐƚĞŶĞŵĞŶŝŶĚĞĐŽŵŵŝƐƐŝĞ͘ ĞƐƚĞDĞŶŐ&ŽŶŐ͕ŚƐĂŶĞŶĚǁŝŶ͕ŚĞĞůĞƌŐďĞĚĂŶŬƚǀŽŽƌĂůũƵůůŝĞŚƵůƉďŝũĚĞƉĞƚͬĐƚƐĐĂŶ͘ KƉŚĞƚůĂĂƚƐƚĞŵŽŵĞŶƚƚŽĐŚŚĞƚƉƌŽŐƌĂŵŵĂǁĞĞƌŽŵŐŽŽŝĞŶĞŶnjĞůĨƐƐĐĂŶŶĞŶŝŶ,ŝůǀĞƌƐƵŵ͕ ŚĞƚǁĂƐũƵůůŝĞŶŽŽŝƚƚĞǀĞĞů͕ũƵůůŝĞǁĂƌĞŶĂůƟũĚďĞƌĞŝĚŽŵŶĞƚĞǀĞŶĚĂƚƐƚĂƉũĞĞdžƚƌĂƚĞnjĞƩĞŶ͕ ǁĂĂƌǀŽŽƌ E<͊ DĞŶŐ &ŽŶŐ͕ njŽŶĚĞƌ Ăů ũŽƵǁ ĞdžƚƌĂ ŝŶnjĞƚ ŵĞƚ ďĞƚƌĞŬŬŝŶŐ ƚŽƚ ĚĞ ƐĐĂŶƐ ŝŶ ,ŝůǀĞƌƐƵŵĞŶŚĞƚǀ>ǁĂƐĚŝƚŶŽŽŝƚŐĞůƵŬƚ͘ ůůĞŵĞĚĞǁĞƌŬĞƌƐǀĂŶŚĞƚƚƌŝĂůďƵƌĞĂƵ͕ďĞĚĂŶŬƚǀŽŽƌŚĞƚĮũŶĞƐĂŵĞŶǁĞƌŬĞŶ͘>ŝĞǀĞ>ŝĞƐďĞƚŚ ĞŶ >ŝŶĚĂ͕ ĚĞ ŶŝƚƐĐŚŬŽǁ ǁĂƐ ĞĞŶ ůĂƐƟŐĞ ƐƚƵĚŝĞ͕ ŵĂĂƌ ǁĞ ŚĞďďĞŶ Ğƌ ƐĂŵĞŶ ƚŽĐŚ ŵĂĂƌ ůŝĞĨƐƚϲϯƉĂƟĞŶƚĞŶŝŶŐĞŬƌĞŐĞŶ͕ĚŝƚŽŽŬǀĂŶǁĞŐĞĚĞŐŽĞĚĞƐĂŵĞŶǁĞƌŬŝŶŐŵĞƚũƵůůŝĞ͊>ŝŶĚĂ͕ ĚĂĂƌŶĂĂƐƚƐƚŽŶĚũŝũĂůƟũĚŬůĂĂƌŽŵďůŽĞĚƚĞƉƌŝŬŬĞŶĂůƐĚŝƚŵŝũǁĞĞƌĞĞŶƐŶŝĞƚůƵŬƚĞ͕ŵŝũŶĚĂŶŬ ŝƐŐƌŽŽƚ͊

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Dankwoord ĞƐƚĞ ĐŽůůĞŐĂ͛Ɛ ǀĂŶ 'ϭ͘ ĞĚĂŶŬƚ ǀŽŽƌ ĚĞ ŐĞnjĞůůŝŐĞ ƟũĚ ŽƉ ũƵůůŝĞ ůĂď njŽǁĞů ƟũĚĞŶƐ ŵŝũŶ ǁĞƚĞŶƐĐŚĂƉƉĞůŝũŬĞ ƐƚĂŐĞ ĂůƐ ĂĨŐĞůŽƉĞŶ ũĂƌĞŶ͘ >ŝĞǀĞ :ŽƌŐĞ͕ ďĞĚĂŶŬƚ ǀŽŽƌ ũĞ ŚƵůƉ ŵĞƚ ŚĞƚ ĂŶĂůLJƐĞƌĞŶ ǀĂŶ ĚĞ E ŵƵƚĂƟĞƐ ǀŽŽƌ ĚĞ /E&>D ƐƚƵĚŝĞ͘ Ŷ ĚĂŶ ŝŶ ŚĞƚ ďŝũnjŽŶĚĞƌ ůŝĞǀĞ DŝƌĂŶĚĂ͕ĂůũŽƵǁŚƵůƉŵĞƚŵŝũŶƐƚƵĚŝĞƐ͕ŶŽŽŝƚƚĞďĞƌŽĞƌĚŽŵĞĞŶĞdžƚƌĂƐƚĂƉƚĞnjĞƩĞŶĞŶ ĂůƐ Ğƌ ŝĞƚƐ ĂĨ ŵŽĞƐƚ ĚĂŶ ǁĂƐ ŚĞƚ ĂůƟũĚ ƐŶĞů ŬůĂĂƌ͘ ŽŶĚĞƌ ũŽƵǁ ŚƵůƉ ǁĂƐ Ěŝƚ ŶŽŽŝƚ ŐĞůƵŬƚ͕ ǁĂĂƌǀŽŽƌĚĂŶŬ͊ ĞƐƚĞ ĐŽůůĞŐĂ͛Ɛ ǀĂŶ &ϰ͖ &ϰ ŝƐ ŶŝĞƚ ŐĞǁŽŽŶ ĞĞŶ ǀĞƌĚŝĞƉŝŶŐ ŝŶ ŚĞƚ D͕ Ěŝƚ ǁŽŽƌĚ njĞŐƚ njŽǀĞĞůŵĞĞƌ͘&ϰ͕ĞĞŶŐƌŽĞƉWŚƐƚƵĚĞŶƚĞŶǀĂŶĚĞǀĂƐĐƵůĂŝƌĞŐĞŶĞĞƐŬƵŶĚĞĚŝĞƐƚĂĂƚǀŽŽƌ ŐĞnjĞůůŝŐŚĞŝĚ ŵĂĂƌŽŽŬĂůƟũĚ ǀŽŽƌĞůŬĂĂƌŬůĂĂƌƐƚĂĂƚŝŶĚŝĞŶ ŶŽĚŝŐ͖ĚĞǁŝŶƚĞƌƐƉŽƌƚĞŶĞŶĚĞ ǀĞůĞďŽƌƌĞůƐnjĂůŝŬŶŝĞƚƐŶĞůǀĞƌŐĞƚĞŶ͘,ŽƵĚĞnjĞŐĞnjĞůůŝŐŚĞŝĚĞƌŝŶ͕ŽŽŬĂůnjŝƩĞŶũƵůůŝĞƐƚƌĂŬƐ ǀĞƌĚĞĞůĚ ŽǀĞƌ ǀĞƌƐĐŚŝůůĞŶĚĞ ƌƵŝŵƚĞŶ͘ >ŝĞǀĞ DĞƌĞů͕ ŬĂŵĞƌŐĞŶŽŽƚ ǀŽŽƌ ĚĞ ůĂĂƚƐƚĞ ϭ͘ϱ ũĂĂƌ͕ ďĞĚĂŶŬƚǀŽŽƌĚĞĮũŶĞŐĞƐƉƌĞŬŬĞŶ͕njŽǁĞůŽǀĞƌĚĞůĞƵŬĞĂůƐŽŽŬŽǀĞƌĚĞŵŝŶĚĞƌůĞƵŬĞnjĂŬĞŶ ŝŶŚĞƚůĞǀĞŶ͘ZƵƚŐĞƌ͕ƐĂŵĞŶďĞŐŽŶŶĞŶŝŶĚĞďĞnjĞŵŬĂƐƚĞŶŽŽŬƚĞŐĞůŝũŬŬůĂĂƌ͘ĞĚĂŶŬƚǀŽŽƌ ũĞŐĞnjĞůůŝŐŚĞŝĚĞŶƐƚĞƵŶĂĨŐĞůŽƉĞŶũĂƌĞŶ͊DĂƵƌŝĐĞ͕ŶŶĞŇĞƵƌ͕EŝĐŽůŝĞŶ͕'ƵŝĚŽ͕ZĞŶƐ͕>ƵƵŬ ĞŶdŚŝũƐ͕ďĞĚĂŶŬƚǀŽŽƌĚĞŐĞnjĞůůŝŐŚĞŝĚ͊dĂŶũĂ͕ďĞĚĂŶŬƚǀŽŽƌŚĞƚƐŽĞƉĞůďĞŐĞůĞŝĚĞŶǀĂŶĚĞ ĂĚŵŝŶŝƐƚƌĂƟĞǀĞŶĂĐŚƚŵĞƌƌŝĞĚŝĞŽŽŬŶŽŐďŝũƉƌŽŵŽǀĞƌĞŶďůŝũŬƚƚĞŚŽƌĞŶ͘ ŶĚĂŶŶĂƚƵƵƌůŝũŬŶŽŐĚĞ͚ƌŝŬŐƌŽĞƉ͖͛>ŽƩĞ͕<ĂŶŐĞŶZĞŶĂƚĞ͕ďĞĚĂŶŬƚǀŽŽƌĂůŚĞƚƐƉĂƌƌĞŶ ĂĨŐĞůŽƉĞŶ ũĂƌĞŶ ŽǀĞƌ ƌĞƐƵůƚĂƚĞŶ ǀĂŶ ƐƚƵĚŝĞƐ ĞŶ ŶĂƚƵƵƌůŝũŬ ĚĞ ŐĞnjĞůůŝŐŚĞŝĚ͘ :ĞīƌĞLJ ĞŶ :ĂŶ͕ ďĞĚĂŶŬƚǀŽŽƌĂůũƵůůŝĞŚƵůƉŽƉůĂďŐĞďŝĞĚ͕ũƵůůŝĞnjŝũŶŽŶŵŝƐďĂĂƌďŝŶŶĞŶĚĞŐƌŽĞƉ͊EŝĂŶnjĂĞŶ DĂŶŽƵƐŚ͕ƐƵĐĐĞƐĂĂŶŬŽŵĞŶĚĞũĂƌĞŶ͊^ŝƌŽŽŶ͕ŽŶĚĞƌƚƵƐƐĞŶŶŝĞƚŵĞĞƌǁĞƌŬnjĂĂŵŝŶŚĞƚD͕ ŵĂĂƌŝŬŚĞďŽŶƚnjĞƩĞŶĚǀĞĞůǀĂŶũĞŐĞůĞĞƌĚŽǀĞƌŽŶĚĞƌnjŽĞŬĚŽĞŶ͕ďĞĚĂŶŬƚ͊ >ŝĞǀĞ ƉĂƌĂŶŝŵĨĞŶ͕ ůŝĞǀĞ ĂƌŽůŝŶĞ͕ ĂĨŐĞůŽƉĞŶ Ϯ ũĂĂƌ ĐŽůůĞŐĂ͛Ɛ ŐĞǁĞĞƐƚ ŝŶ ŚĞƚ D͕ ŵĂĂƌ ŽŽŬ ďƵŝƚĞŶ ŚĞƚ D njŝũŶ ǁŝũ ŽŶĚĞƌƚƵƐƐĞŶ ǀƌŝĞŶĚŝŶŶĞŶ͘ ĂƉƉƵĐŚŝŶŽ͛Ɛ ĚƌŝŶŬĞŶ ŽƉ ŚĞƚ ǀŽĞƚĞŶƉůĞŝŶ͕ ĞĞŶ ŬĂŵĞƌ ĚĞůĞŶ ŝŶ WƌĂĂŐ ĞŶ >ŝƐƐĂďŽŶ͕ ŽĨ ƐĂǀŽŶĚƐ ƐĂŵĞŶ ĞƚĞŶ na een lange werkdag. Bedankt voor al je gezelligheid en steun afgelopen jaren. >ŝĞǀĞsŝĐŬLJ͕ĂůǀƌŝĞŶĚŝŶŶĞŶnjŽůĂŶŐŝŬŵĞŬĂŶŚĞƌŝŶŶĞƌĞŶ͘KƉĚĞďĂƐŝƐƐĐŚŽŽůĞŶĚĞŵŝĚĚĞůďĂƌĞ ƐĐŚŽŽů ŽŶĂĨƐĐŚĞŝĚĞůŝũŬ͕ ƉĂƐ ƚŽĞŶ ǁĞ ŐŝŶŐĞŶ ƐƚƵĚĞƌĞŶ ǀŽůŐĚĞŶ ǁĞ ĂůůĞďĞŝ ĞĞŶ ĂŶĚĞƌ ƉĂĚ͘ 'ĞůƵŬŬŝŐnjŝũŶǁŝũŶŽŐƐƚĞĞĚƐŐŽĞĚĞǀƌŝĞŶĚŝŶŶĞŶĞŶĚŽĞŶǁĞŶŽŐƌĞŐĞůŵĂƟŐůĞƵŬĞĚŝŶŐĞŶ͘ ĞĚĂŶŬƚĚĂƚũĞĂůƟũĚǀŽŽƌŵĞŬůĂĂƌƐƚĂĂƚ͘ >ŝĞǀĞnjƵƐƐĞŶ͕ǀĞůLJŶĞĞŶDĂƌůĞĞŶ͘>ŝĞǀĞ&ƌĂŶŬ͕ŽŽŬũŝũŚŽŽƌƚƐŝŶĚƐŵĞŶƐĞŶŚĞƵŐĞŶŝƐďŝũĚĞ ĨĂŵŝůŝĞĞŶďĞŶƚǀŽŽƌŵŝũĂůƐĞĞŶďƌŽĞƌ͘KŶĚĂŶŬƐŽŶnjĞĚƌƵŬŬĞŚĞĐƟƐĐŚĞůĞǀĞŶƐŝƐŚĞƚĂůƟũĚ ǁĞĞƌŐĞnjĞůůŝŐĂůƐǁĞŵĞƚnj͛ŶĂůůĞŶďŝũĞůŬĂĂƌnjŝũŶ͘ůŬũĂĂƌŵĞƚŚĞƚŐĞnjŝŶŽƉǁŝŶƚĞƌƐƉŽƌƚ͕ĚŝƚŝƐ ƚŽĐŚĂůƟũĚǁĞĞƌĞĞŶĨĞĞƐƚĞŶŝĞƚƐŽŵŶĂĂƌƵŝƚƚĞŬŝũŬĞŶ͘ĞĚĂŶŬƚŚŝĞƌǀŽŽƌ͊

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>ŝĞǀĞƉĂƉĞŶŵĂŵ͕njŽŶĚĞƌũƵůůŝĞŚĂĚŝŬĚŝƚĚĂŶŬǁŽŽƌĚŶŽŽŝƚŐĞƐĐŚƌĞǀĞŶ͘:ƵůůŝĞŚĞďďĞŶŵŝũ ŽƉŐĞǀŽĞĚƚŽƚĚĞĚŽŽƌnjĞƩĞƌĚŝĞŝŬŶƵďĞŶĞŶũƵůůŝĞŚĞďďĞŶŵŝũŐĞůĞĞƌĚŽŵĂůƟũĚƚĞƉƌŽďĞƌĞŶ ŚĞƚ ďĞƐƚĞ Ƶŝƚ ŵĞnjĞůĨ ƚĞ ŚĂůĞŶ͘ :ƵůůŝĞ ŚĞďďĞŶ ĂůƟũĚ ĂĐŚƚĞƌ ŵŝũŶ ďĞƐůŝƐƐŝŶŐĞŶ ŐĞƐƚĂĂŶ ĞŶ ŵŝũŚŝĞƌŝŶŐĞƐƚĞƵŶĚ͕njĞůĨƐƚŽĞŶŝŬƚŽĐŚďĞƐůŽŽƚŽŵǀŽŽƌĚĞĚĞƌĚĞŬĞĞƌŵĞĞƚĞůŽƚĞŶǀŽŽƌ ŐĞŶĞĞƐŬƵŶĚĞ͕ ďĞĚĂŶŬƚ ŚŝĞƌǀŽŽƌ͊ Ŷ ƉĂƉ͕ ũĞ njŝĞƚ ŚĞƚ͕ ũĞ ĂŶŐƐƚ ĚĂƚ ŝŬ njŽŶĚĞƌ ĚŝƉůŽŵĂ njŽƵ afzwaaien is nu dubbel ongegrond.

Ŷ ĂůƐ ĂůůĞƌůĂĂƚƐƚĞ ůŝĞǀĞ :ƵůŝĂŶ͕ ŵŝũŶ ƌŽƚƐ ŝŶ ĚĞ ďƌĂŶĚŝŶŐ͘ /Ŭ njĂů ŶŽŽŝƚ ƐƉŝũƚ ŚĞďďĞŶ ǀĂŶ ĚĞ ďĞƐůŝƐƐŝŶŐŽŵƚĞƉƌŽŵŽǀĞƌĞŶďŝũĚĞǀĂƐĐƵůĂŝƌĞŐĞŶĞĞƐŬƵŶĚĞ͕ǁĂŶƚŚŝĞƌŚĞďŝŬũŽƵŽŶƚŵŽĞƚ͊ ĨŐĞůŽƉĞŶũĂƌĞŶǁĂƐũŝũŵŝũŶƐƚŽŬĂĐŚƚĞƌĚĞĚĞƵƌŽŵƚŽĐŚĂůƟũĚǁĞĞƌĚŽŽƌƚĞnjĞƩĞŶ͕ŽŶĚĂŶŬƐ ĞĞŶŝĞƚƐŵŝŶĚĞƌŐƌŽƚĞǁĞƚĞŶƐĐŚĂƉƉĞůŝũŬĞĂŵďŝƟĞĚĂŶŝŬǀĂŶƚĞǀŽƌĞŶŐĞĚĂĐŚƚŚĂĚ͘ŽŶĚĞƌ ũŽƵǁƐƚĞƵŶǁĂƐĚŝƚŶŝĞƚŐĞůƵŬƚ͘tŝũŚĞďďĞŶŶƵƐĂŵĞŶĞĞŶĮũŶŚƵŝƐ͕ĞĞŶŚĞĞƌůŝũŬĞƉůĞŬŽŵŶĂ ĞĞŶǁĞƌŬĚĂŐǁĞĞƌƚŚƵŝƐƚĞŬŽŵĞŶ͊

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