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

Brain retraction injury after elective aneurysm clipping: a retrospective single-center cohort study

Background: BRI is estimated to occur in 10% of skull-base surgery and 5% of aneurysm surgery. These estimates are based on a few studies with unclear methodology. The purpose of this study is to assess the rate of BRI occurrence, its risk factors, and the association between BRI and postoperative focal neurological deficit in patients that underwent elective aneurysm surgery in a single institution. Methods: All patients that underwent elective aneurysm surgery in a single tertiary center in the Netherlands were included. BRI was defined as cortical hypodensities in the surgical trajectory not matching areas of large arterial infarction. Risk ratios were calculated between BRI and (a) the use of temporary parent artery occlusion during clipping, (b) anterior communicating artery (ACom), and (c) middle cerebral artery (MCA) location of the aneurysm, (d) presence of mentioned CVA risk factors, (e) the clipping of > 1 aneurysm during the same procedure, and (f) new focal neurological deficit. Statistical analysis further included t-tests and binary logistical regression analysis on the correlation between age and BRI. Results: BRI was identified postoperatively in 42 of the 94 patients included in this study. A new focal neurological deficit was found in 7 patients in the BRI group. A total of 5 patients had persisting symptoms at 3-month follow-up, of which 2 were caused by BRI. Increasing age is a risk factor for developing BRI. Conclusions: The high rate of BRI and significant risk of new postoperative focal neurological deficit in our patients should be considered when counseling patients for elective aneurysm surgery

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

Lumbar puncture for treating acute hydrocephalus after aneurysmal subarachnoid haemorrhage

Background: External ventricular drainage (EVD) for acute hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH) carries a risk of complications. We studied the proportion of patients in whom EVD can be avoided by treating acute hydrocephalus with ≥1 lumbar punctures (LP). Methods: From a prospectively collected database, we retrieved data on all aSAH patients admitted between 2007 and 2017 who developed acute hydrocephalus (i.e. neurological deterioration and ventricular enlargement <72 h after aSAH). Our regime is to consider LP as initial treatment. We calculated the proportions of patients (with corresponding 95% confidence interval (CI)) who improved after the initial LP and the extent of clinical improvement, the proportions of patients who were treated with only ≥1 LP(s), and those of patients needing continuous external ventricular or external lumbar drainage, or permanent ventriculoperitoneal or lumboperitoneal drainage. Results: Of 1391 consecutive aSAH patients, 473 (34%) had acute hydrocephalus, of whom 388 (82%) were treated. Of the 86 patients with LP as initial treatment, 70 (81% [95% CI 72–88]) showed initial improvement (with increase in median Glasgow Coma Score from 10 (IQR 7–12) to 12 (IQR 9–14) after initial LP), 39 (45% [95% CI 35–56]) improved with LP only, 41 (48% [95% CI 37–58]) needed continuous drainage and six (7% [95% CI 3–14]) needed permanent drainage. Conclusion: Around half the patients treated with LP for deterioration from acute hydrocephalus after aSAH does not require continuous extraventicular or extralumbar drainage

Long-term feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a pig model

Background: High flow bypass surgery can be a last resort procedure for patients suffering from complex neurovascular pathology. Temporary occlusion of a recipient artery in these patients could result in debilitating neurological deficits. We developed a sutureless, mechanical anastomotic connection device, the SELANA clip (Sutureless Excimer Laser-Assisted Non-occlusive Anastomosis clip: SEcl). In the present study, we aim to determine the long-term non-inferiority of the SEcl technique compared with historical data of the conventional ELANA anastomosis technique. Methods: A total of 18 SEcl bypasses were created on the carotid artery in a porcine model in 6 different survival groups. Mean application times, flap retrieval rates, hemostasis, patency, flow, endothelialization, and remodeling were assessed. Results: The mean application time of the SEcl anastomoses was 15.2 ± 9.6 min, which was faster compared with the conventional ELANA anastomoses. The flap retrieval rate of the SEcl anastomoses was 86% (32/37). Direct hemostasis was achieved in 89% (33/37) SEcl anastomoses. Patency in all surviving animals was 94% (17/18). Bypass flow after six months was 156.5 ± 24.7 mL/min. Full endothelialization of the SEcl pins was observed after 3 weeks. Conclusion: The SEcl technique is not inferior to the ELANA technique regarding patency, flap retrieval rate, flow, and endothelialization. On the basis of a significantly shorter application time and superior hemostasis, the SEcl technique could be preferable over the ELANA technique. A pilot study in patients is a logical next step based on our current results