VLSI top-down design based on the separation of hierarchies

Despite the presence of structure, interactions between the three views on VLSI design still lead to lengthy iterations. By separating the hierarchies for the respective views, the interactions are reduced. This separated hierarchy allows top-down design with functional abstractions as exemplified by an experimental self-timed CMOS RISC computer design

Costs and clinical effectiveness in the surgical treatment of cervical radiculopathy

The general aim of this dissertation was to evaluate surgical treatments for patients with cervical radiculopathy in terms of clinical outcomes and cost-effectiveness. Cervical radiculopathy refers to arm pain caused by compression of a nerve in the neck. Currently, there is no established optimal surgical treatment in the scientific literature. Various surgical approaches are available, with surgeons currently favoring an anterior approach (front of the neck). Another option is the posterior approach ( back of the neck). Potential advantages of the posterior approach include proximity to fewer critical structures (such as the carotid artery and esophagus in the front), no need for artificial materials, and potential cost savings.The main focus of the dissertation is a study conducted in 9 hospitals in the Netherlands, where patients were randomly assigned to undergo either anterior or posterior surgery. The results of the study demonstrate that posterior surgery is not inferior to anterior surgery. Additionally, posterior surgery is cheaper and therefore likely cost-effective compared to anterior surgery. These findings play a significant role in the treatment of patients with cervical radiculopathy and support the idea that despite surgeons' preference for the anterior approach, patients should be informed about both approaches

Family Nursing Conversations in Home Health Care:supporting family functioning and preventing caregiver burden in long-term care situations

In an ageing population, fewer health care professionals are available for the increasing number of people in need of care. Professional care, therefore, needs to be efficient and include family caregivers. Intensive and long-term family caregiving can result in caregiver burden and impaired family functioning. In her PhD thesis, Susanne Broekema shows that family nursing conversations in home health care can improve family functioning and prevent caregiver burden, without increasing the need for professional care. Participants in a family nursing conversation are the nurse, the care recipient, and the family members or other close ones. Together, they explore the network and the situation. Each participant’s perspective is included in the conversation. The nurse structures the conversation, encourages open communication, and acknowledges painful experiences, emotions, and also the family’s strengths. The participants work towards a shared approach of the care situation. The research showed that nurses were well able to conduct family nursing conversations, after participating in an educational intervention. In interviews, families explained that the conversation resulted in increased overview of the situation and improved quality of contact. In the longer term, family members mentioned decreased burden and a better match between the care and both their capacities and the needs of the care recipient. A comparison between families that participated in two family nursing conversations and families that only received the usual home health care, again showed the positive influence of the conversations on family functioning and caregiver burden. In addition, these families required less professional home health care

Fine-mapping variants and genes that contribute to celiac disease

Complex diseases like type-1 diabetes, multiple sclerosis, and celiac disease (CeD) are difficult to unravel from a genetic perspective because they are caused by many mutations (DNA variants) that can be present in many different combinations. This is further complicated by the fact that over 95% of these variants are located in non-coding DNA, making it difficult to identify which genes they affect. Hence, in this thesis we applied cutting-edge, high-throughput fine-mapping methods to identify the variants, genes, non-coding regulatory elements, and cell states that contribute to CeD. We developed the high-throughput method Survey of Regulatory Elements and SNPs (SuRE-SNP) that tests over 400 million plasmids (small circular DNA of interest) in multiple CeD-associated cell-types to identify which non-coding CeD-associated locations and variants have gene regulatory potential. SuRE-SNP identified hundreds of non-coding regulatory elements in epithelial cells, of which three contain CeD-associated variants that we validated to strongly alter their regulatory potential. In a second fine-mapping project, we explored the binding of STAT proteins to DNA in CD8+ intraepithelial lymphocytes (IELs) under CeD-specific stimulations. We identified a possible central regulatory role for STATs in CD8+ IELs during CeD-specific stimulations. Moreover, we identified a possible role for T-cell stimulation in cytotoxic activation of CD8+ IELs. A total of 73 CeD-associated genes that are regulated by STATs and play a role in the activation of CD8+ IELs were prioritized, including the RGS1 gene whose gene expression can be disrupted by a STAT-binding CeD-associated variant