Maternal Illness at the Limits of Fetal Viability

Groot, C.J.M. de [Promotor]Bolte, A.C. [Copromotor]Zeeman, G.G. [Copromotor

Spiral surface growth without desorption

Spiral surface growth is well understood in the limit where the step motion is controlled by the local supersaturation of adatoms near the spiral ridge. In epitaxial thin-film growth, however, spirals can form in a step-flow regime where desorption of adatoms is negligible and the ridge dynamics is governed by the non-local diffusion field of adatoms on the whole surface. We investigate this limit numerically using a phase-field formulation of the Burton-Cabrera-Frank model, as well as analytically. Quantitative predictions, which differ strikingly from those of the local limit, are made for the selected step spacing as a function of the deposition flux, as well as for the dependence of the relaxation time to steady-state growth on the screw dislocation density.Comment: 9 pages, 3 figures, RevTe

Induction of Labor for Maternal Indications at a Periviable Gestational Age; Survey on Management, Reporting and Auditing amongst Dutch Maternal-Feta Medicine Specialists and Neonatologists

Background In cases of life-threatening maternal conditions in the periviable period, professionals may consider immediate delivery with fetal demise as a consequence of the treatment. We sought the opinion of involved medical professionals on management, reporting, and auditing in these cases.Methods We performed an online survey amongst all registered maternal-fetal medicine (MFM) specialists and neonatologists in the Netherlands. The survey presented two hypothetical cases of severe early-onset pre-eclampsia at periviable gestational ages. Management consisted of immediate termination or expectant management directed towards newborn survival.Findings In the case managed by immediate termination, 62% percent answered that fetal demise resulting from induction of labor for maternal indications should be audited only within the medical profession. In the case of expectant management, 17% of the participants agreed with this management. Some answers revealed a significant difference in opinion between the medical specialists.Conclusion Perspective of MFM specialists and neonatologists differs with regard to counseling prospect parents in case of severe early onset pre-eclampsia. The majority of professionals is willing to report late termination (after 24 weeks' gestation) for severe maternal disease to medical experts for internal audits but not for legal auditing.</p

Impurity-induced diffusion bias in epitaxial growth

We introduce two models for the action of impurities in epitaxial growth. In the first, the interaction between the diffusing adatoms and the impurities is ``barrier''-like and, in the second, it is ``trap''-like. For the barrier model, we find a symmetry breaking effect that leads to an overall down-hill current. As expected, such a current produces Edwards-Wilkinson scaling. For the trap model, no symmetry breaking occurs and the scaling behavior appears to be of the conserved-KPZ type.Comment: 5 pages(with the 5 figures), latex, revtex3.0, epsf, rotate, multico

Current-Induced Step Bending Instability on Vicinal Surfaces

We model an apparent instability seen in recent experiments on current induced step bunching on Si(111) surfaces using a generalized 2D BCF model, where adatoms have a diffusion bias parallel to the step edges and there is an attachment barrier at the step edge. We find a new linear instability with novel step patterns. Monte Carlo simulations on a solid-on-solid model are used to study the instability beyond the linear regime.Comment: 4 pages, 4 figure

Vision and Foraging in Cormorants: More like Herons than Hawks?

Background Great cormorants (Phalacrocorax carbo L.) show the highest known foraging yield for a marine predator and they are often perceived to be in conflict with human economic interests. They are generally regarded as visually-guided, pursuit-dive foragers, so it would be expected that cormorants have excellent vision much like aerial predators, such as hawks which detect and pursue prey from a distance. Indeed cormorant eyes appear to show some specific adaptations to the amphibious life style. They are reported to have a highly pliable lens and powerful intraocular muscles which are thought to accommodate for the loss of corneal refractive power that accompanies immersion and ensures a well focussed image on the retina. However, nothing is known of the visual performance of these birds and how this might influence their prey capture technique. Methodology/Principal Findings We measured the aquatic visual acuity of great cormorants under a range of viewing conditions (illuminance, target contrast, viewing distance) and found it to be unexpectedly poor. Cormorant visual acuity under a range of viewing conditions is in fact comparable to unaided humans under water, and very inferior to that of aerial predators. We present a prey detectability model based upon the known acuity of cormorants at different illuminances, target contrasts and viewing distances. This shows that cormorants are able to detect individual prey only at close range (less than 1 m). Conclusions/Significance We conclude that cormorants are not the aquatic equivalent of hawks. Their efficient hunting involves the use of specialised foraging techniques which employ brief short-distance pursuit and/or rapid neck extension to capture prey that is visually detected or flushed only at short range. This technique appears to be driven proximately by the cormorant's limited visual capacities, and is analogous to the foraging techniques employed by herons

Phase transitions in the antiferromagnetic XY model with a kagome lattice

The ground state of the antiferromagnetic XY model with a kagome lattice is characterized by a well developed accidental degeneracy. As a consequence the phase transition in this system consists in unbinding of pairs of fractional vortices. Addition of the next-to-nearest neighbors (NNN) interaction leads to stabilization of the long-range order in chirality (staggered chirality). We show that the phase transition, related with destruction of this long-range order, can happen as a separate phase transition below the temperature of the fractional vortex pairs unbinding only if the NNN coupling is extremely weak, and find how the temperature of this transition depends on coupling constants. We also demonstarte that the antiferromagnetic ordering of chiralities and, accordingly, the presence of the second phase transition are induced by the free energy of spin wave fluctuations even in absence of the NNN coupling.Comment: 10 pages (Revtex) + 8 figures (in 2 postscript files

Feasibility of therapeutic drug monitoring of sorafenib in patients with liver or thyroid cancer

Introduction: Sorafenib is a tyrosine-kinase inhibitor approved for the treatment of renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, and desmoid fibromatosis. As high inter-individual variability exists in exposure, there is a scientific rationale to pursue therapeutic drug monitoring (TDM). We investigated the feasibility of TDM in patients on sorafenib and tried to identify sub-groups in whom pharmacokinetically (PK) guided-dosing might be of added value. Methods: We included patients who started on sorafenib (between October 2017 and June 2020) at the recommended dose of 400 mg BID or with a step-up dosing schedule. Plasma trough levels (Ctrough) were measured at pre-specified time-points. Increasing the dose was advised if Ctrough was below the target of 3750 ng/mL and toxicity was manageable. Results: A total of 150 samples from 36 patients were collected. Thirty patients (83 %) had a Ctrough below the prespecified target concentration at a certain time point during treatment. Toxicity from sorafenib hampered dosing according to target Ctrough in almost half of the patients. In 11 patients, dosing was adjusted based on Ctrough. In three patients, this resulted in an adequate Ctrough without additional toxicity four weeks after the dose increase. In the remaining eight patients, dose adjustment based on Ctrough did not result in a Ctrough above the target or caused excessive toxicity. Conclusions: TDM for sorafenib is not of added value in daily clinical practice. In most cases, toxicity restricts the possibility of dose escalations.</p

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. Methods: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. Results: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. Conclusions: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.</p