Although anti-cancer treatments have significantly advanced over the past decades, obstacles to accomplishing successful treatment still exist. The occurrence of treatment resistance is one of the... Show moreAlthough anti-cancer treatments have significantly advanced over the past decades, obstacles to accomplishing successful treatment still exist. The occurrence of treatment resistance is one of the major factors that limit the long-lasting efficacy of anti-cancer treatment. Additionally, substantial variability in pharmacokinetics (PK) / pharmacodynamics (PD) of anti-cancer drugs also challenges successful oncology treatment. Therefore, gaining knowledge of and ultimately better suppressing evolutionary resistance development during treatment, and applying personalized treatment are desired to improve anti-cancer treatment. In this thesis, we have applied quantitative modeling approaches to address these needs, aiming for improved treatment for oncology patients. Our work demonstrated that with the quantitative models, the evolutionary progression of tumors could be characterized and predicted, accounting for interactions among heterogeneous tumor cells and supported by mutant gene variants detected in circulating tumor DNA (ctDNA). In addition, we developed population PK /PD models which enabled quantitative description of the PK and PD of anti-cancer drugs and corresponding variabilities in real-world patients. The developed models have been further applied to support the identification of optimal treatment strategies and guide individualized treatment for oncology patients. Show less
Egypt became a province of the Persian or Achaemenid Empire in 526 BC. In the decades thereafter, some inhabitants of the Delta and Nile Valley rebelled against their Persian overlords. Though... Show moreEgypt became a province of the Persian or Achaemenid Empire in 526 BC. In the decades thereafter, some inhabitants of the Delta and Nile Valley rebelled against their Persian overlords. Though these rebellions are well known, they have been little studied. The present thesis provides an in-depth study of the first two rebellions of Persian-Period Egypt: the rebellion that began in ca. 521 BC, and which may have lasted until 519/18 BC, and the rebellion that began in ca. 487/86 BC, and which may have lasted until 485/84 BC. Show less
Dit proefschrift behandeld allerlei klinische vragen waarmee de arts geconfronteerd wordt als een volwassene zich presenteert met een gecompliceerde urineweginfectie. In verschillende hoofdstukken... Show moreDit proefschrift behandeld allerlei klinische vragen waarmee de arts geconfronteerd wordt als een volwassene zich presenteert met een gecompliceerde urineweginfectie. In verschillende hoofdstukken wordt ingegaan op de volgende vragen: Wanneer moet de pati_nt worden opgenomen? Wanneer dient rekening te worden gehouden met een resistent oorzakelijk micro-organisme? Wanneer is radiologisch onderzoek van de urinewegen nuttig? Wanneer heeft een bloedkweek toegevoegde waarde naast een urinekweek? Hoe lang dient te worden behandeld met antibiotica? Daarnaast wordt de relatie tussen urineweginfecties en de functie van de bekkenbodem beschreven. Show less
Antimicrobial resistance of bacteria is a worldwide and ever-growing problem, directly linked to the use of antimicrobial drugs. Resistant bacteria emerge under the selective pressure of... Show moreAntimicrobial resistance of bacteria is a worldwide and ever-growing problem, directly linked to the use of antimicrobial drugs. Resistant bacteria emerge under the selective pressure of antibiotics. In hospitals, where large-scale usage of antibiotics is common, bacteria frequently become resistant to several antibiotics which causes serious problems for the treatment of patients with infections by these microorganisms. Well-known (multi)-resistant bacteria causing problems in many countries all over the world are methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, penicillin-resistant pneumococci, extended-spectrum betalactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, and multiresistant Mycobacterium tuberculosis Show less
