The immune compartment at the maternal-fetal interface throughout human pregnancy

During pregnancy a unique situation arises in which the mother's immune system accepts the fetus, which carries both maternal and paternal genes, and does not reject it as can occur in solid organ transplantation. The aim of this dissertation was to unravel the immunological mechanisms that ensure tolerance during a healthy pregnancy and uncover how alterations could contribute to the development of pregnancy complications, such as pre-eclampsia and preterm birth.We applied the new technique mass cytometry and the associated computational analyzes to map all immune cells of the mother during a healthy pregnancy. Furthermore, we demonstrated the presence of three types of functional regulatory CD4+ T cells, identified a phenotype of CD8+ T cells that can offer both tolerance and immunity against infections, and demonstrated potential cross-reactivity of T cells against fetal allo-antigens. The results described in this thesis have contributed to a better understanding of healthy pregnancies and form a basis on which further research can be built.LUMC / Geneeskund

On the Role of Penning Ionization in Photoassociation Spectroscopy

We study the role of Penning ionization on the photoassociation spectra of He(^3S)-He(^3S). The experimental setup is discussed and experimental results for different intensities of the probe laser are shown. For modelling the experimental results we consider coupled-channel calculations of the crossing of the ground state with the excited state at the Condon point. The coupled-channel calculations are first applied to model systems, where we consider two coupled channels without ionization, two coupled channels with ionization, and three coupled channels, for which only one of the excited states is ionizing. Finally, coupled-channel calculations are applied to photoassociation of He(^3S)-He(^3S) and good agreement is obtained between the model and the experimental results.Comment: 14 pages, 18 figures, submitted to the special issue on Cold Molecules of J. Phys.

Climate model boundary conditions for four Cretaceous time slices

International audienceGeneral circulation models (GCMs) are useful tools for investigating the characteristics and dynamics of past climates. Understanding of past climates contributes significantly to our overall understanding of Earth's climate system. One of the most time consuming, and often daunting, tasks facing the paleoclimate modeler, particularly those without a geological background, is the production of surface boundary conditions for past time periods. These boundary conditions consist of, at a minimum, continental configurations derived from plate tectonic modeling, topography, bathymetry, and a vegetation distribution. Typically, each researcher develops a unique set of boundary conditions for use in their simulations. Thus, unlike simulations of modern climate, basic assumptions in paleo surface boundary conditions can vary from researcher to researcher. This makes comparisons between results from multiple researchers difficult and, thus, hinders the integration of studies across the broader community. Unless special changes to surface conditions are warranted, researcher dependent boundary conditions are not the most efficient way to proceed in paleoclimate investigations. Here we present surface boundary conditions (land-sea distribution, paleotopography, paleobathymetry, and paleovegetation distribution) for four Cretaceous time slices (120 Ma, 110 Ma, 90 Ma, and 70 Ma). These boundary conditions are modified from base datasets to be appropriate for incorporation into numerical studies of Earth's climate and are available in NetCDF format upon request from the lead author. The land-sea distribution, bathymetry, and topography are based on the 1°×1° (latitude × longitude) paleo Digital Elevation Models (paleoDEMs) of Christopher Scotese. Those paleoDEMs were adjusted using the paleogeographical reconstructions of Ronald Blakey (Northern Arizona University) and published literature and were then modified for use in GCMs. The paleovegetation distribution is based on published data and reconstructions and consultation with members of the paleobotanical community and is represented as generalized biomes that should be easily translatable to many vegetation-modeling schemes

Separation From the Life Partner and Exit From Self-Employment

The survival of businesses in the market often hinges on contributions of the business owner’s household members. Partners of the self-employed as well as their children may, for example, provide emotional support but also cheap and flexible labor. Although the household composition of self-employed individuals has been analyzed in many earlier studies, little is known about what happens to the self-employed individual and his or her business when one separates from a life partner. We argue that separation from a life partner has profound financial and social consequences for the business owner. Specifically, we propose that a decrease in household income and social functioning (which is the degree of interference with social activities due to mental and/or physical problems) after separation from the life partner may lead to an exit from self-employment. Our empirical analysis draws on data from the longitudinal HILDA (Household, Income and Labour Dynamics in Australia) survey, for the period 2002–2017. Based on information from 4,044 self-employed individuals aged 18–64 years (18,053 individual-year observations), we find that separating from the life partner in the past year significantly increases the probability of exit from self-employment in the next year. Furthermore, we find that the positive association between separation from the life partner and exit from self-employment can be explained for 29.7% by a reduction in social functioning and for 10.7% by a reduction in household income. We study five exit routes out of self-employment and find that separation from the life partner mainly increases the probabilities of becoming a wage worker and of re-entering self-employment after experiencing an exit. For exit to unemployment or to a position outside the labor force (voluntarily inactive/retirement or any other non-labor force position), we find insignificant relationships with separation from the life partner. Furthermore, for all exit routes except retirement, we find significant indirect effects implying that decreased household income and levels of social functioning are important mechanisms through which separation from the life partner is related to exit from self-employment

Anesthesia depresses cerebrovascular reactivity to acetazolamide in pediatric moyamoya vasculopathy

Measurements of cerebrovascular reactivity (CVR) are essential for treatment decisions in moyamoya vasculopathy (MMV). Since MMV patients are often young or cognitively impaired, anesthesia is commonly used to limit motion artifacts. Our aim was to investigate the effect of anesthesia on the CVR in pediatric MMV. We compared the CVR with multidelay-ASL and BOLD MRI, using acetazolamide as a vascular stimulus, in all awake and anesthesia pediatric MMV scans at our institution. Since a heterogeneity in disease and treatment influences the CVR, we focused on the (unaffected) cerebellum. Ten awake and nine anesthetized patients were included. The post-acetazolamide CBF and ASL-CVR were significantly lower in anesthesia patients (47.1 ± 15.4 vs. 61.4 ± 12.1, p = 0.04; 12.3 ± 8.4 vs. 23.7 ± 12.2 mL/100 g/min, p = 0.03, respectively). The final BOLD-CVR increase (0.39 ± 0.58 vs. 3.6 ± 1.2% BOLD-change (mean/SD), p Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Clinical and Molecular Profiling to Develop a Potential Prediction Model for the Response to Alemtuzumab Therapy for Acute Kidney Transplant Rejection

Alemtuzumab, a monoclonal antibody that depletes CD52‐bearing immune cells, is an effective drug for the treatment of severe or glucocorticoid‐resistant acute kidney transplant rejection (AR). Patient‐specific predictions on treatment response are, however, urgently needed, given the severe side effects of alemtuzumab. This study developed a multidimensional prediction model with the aim of generating clinically useful prognostic scores for the response to alemtuzumab. Clinical and histological characteristics were collected retrospectively from patients who were treated with alemtuzumab for AR. In addition, targeted gene expression profiling of AR biopsy tissues was performed. Least absolute shrinkage and selection operator (LASSO) logistic regression modeling was used to construct the ALEMtuzumab for Acute Rejection (ALEMAR) prognostic score. Response to alemtuzumab was defined as patient and allograft survival and at least once an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m(2) during the first 6 months after treatment. One hundred fifteen patients were included, of which 84 (73%) had a response to alemtuzumab. The ALEMAR‐score accurately predicted the chance of response. Gene expression analysis identified 13 differentially expressed genes between responders and nonresponders. The combination of the ALEMAR‐score and selected genes resulted in improved predictions of treatment response. The present preliminary prediction model is potentially helpful for the development of stratified alemtuzumab treatment for acute kidney transplant rejection but requires validation