Visualizing immune checkpoints and T cells in patients with cancer

This thesis describes the results of clinical studies using molecular imaging to visualize immune checkpoint molecules and immune cells in patients with solid tumors. These imaging results are used to improve our understanding of the anti-tumor immune response follow immune checkpoint inhibitor therapy and to assess whether these results can predict tumor response to therapy

Multiple myeloma

Multiple myeloma is the second most common haematological malignancy in high-income countries, and typically starts as asymptomatic precursor conditions—either monoclonal gammopathy of undetermined significance or smouldering multiple myeloma—in which initiating genetic abnormalities, such as hyperdiploidy and translocations involving the immunoglobulin heavy chain, are already present. The introduction of immunomodulatory drugs, proteasome inhibitors, and CD38-targeting antibodies has extended survival, but ultimately the majority of patients will die from their disease, and some from treatment-related complications. Disease progression and subsequent relapses are characterised by subclonal evolution and increasingly resistant disease. Patients with multiple myeloma usually have hypercalcaemia, renal failure, anaemia, or osteolytic bone lesions—and a detailed diagnostic investigation is needed to differentiate between symptomatic multiple myeloma that requires treatment, and precursor states. Risk stratification using both patient-specific (eg, performance status) and disease-specific (eg, presence of high-risk cytogenetic abnormalities) is important for prognosis and to define the best treatment strategy. Current research strategies include the use of minimal residual disease assays to guide therapy, refining immunotherapeutic approaches, and intercepting disease early in smouldering multiple myeloma

Designing digital public service supply chains:Four country-based cases in criminal justice

Purpose: Many countries aim to improve public services by use of information and communication technology (ICT) in public service supply chains. However, the literature does not address how inter-organizational ICT is used in redesigning these particular supply chains. The purpose of this paper is to explore this important and under-investigated area. Design/methodology/approach: An explorative multiple-case study was performed based on 36 interviews, 39 documents, extensive field visits and observations providing data on digital transformation in four European criminal justice supply chains. Findings: Two different design approaches to digital transformation were found, which are labelled digitization and digitalization. These approaches are characterized by differences in public service strategies, performance aims, and how specific public characteristics and procedures are dealt with. Despite featuring different roles for ICT, both types show the viable digital transformation of public service supply chains. Additionally, the application of inter-organizational ICT is found not to automatically result in changes in the coordination and management of the chain, in contrast to common assumptions. Originality/value: This paper is one of the first to adopt an inter-organizational perspective on the use of ICT in public service supply chains. The findings have scientific and managerial value because fine-grained insights are provided into how public service supply chains can use ICT in an inter-organizational setting. The study shows the dilemmas faced by and possible options for public organizations when designing digital service delivery

Chytrid epidemics may increase genetic diversity of a diatom spring-bloom

Contrary to expectation, populations of clonal organisms are often genetically highly diverse. In phytoplankton, this diversity is maintained throughout periods of high population growth (that is, blooms), even though competitive exclusion among genotypes should hypothetically lead to the dominance of a few superior genotypes. Genotype-specific parasitism may be one mechanism that helps maintain such high-genotypic diversity of clonal organisms. Here, we present a comparison of population genetic similarity by estimating the beta-dispersion among genotypes of early and peak bloom populations of the diatom Asterionella formosa for three spring-blooms under high or low parasite pressure. The Asterionella population showed greater beta-dispersion at peak bloom than early bloom in the 2 years with high parasite pressure, whereas the within group dispersion did not change under low parasite pressure. Our findings support that high prevalence parasitism can promote genetic diversification of natural populations of clonal hosts

Alternatives for pain: approaches towards personalized pain management

This thesis aims to describe certain novel approaches and pharmacological interventions in the treatment of acute and chronic pain. It demonstrates that the efficacy of the mu-opioid receptor agonist and noradrenaline reuptake inhibitor tapentadol in the treatment of chronic pain is highest in specific patient phenotypes. This highlights the importance of patient phenotyping to get a detailed indication of the characteristics of the different aspects of the pain syndrome (such as involvement and activity of excitatory versus inhibitory pathways) without the need for knowledge on underlying mechanisms or related illnesses. Additionally, it demonstrates that treatment with the non-conventional treatment option cannabis shows potential but efficacy in the chosen patient population was limited. This thesis is also designated to treatment of acute pain with sublingual sufentanil and a non-opioid alternative option (ice-popsicle). Both show efficacy and seem possible alternatives as part of the multimodal therapy of acute pain. Bedrocan Grunenthal B.V.LUMC / Geneeskund

Religie en Onderwijs : over verhoudingen en verbindingen in het publieke domein

Openingsrede Protestantse Theologische Universitei