Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth:the Rotterdam Periconception Cohort

STUDY QUESTION: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles?SUMMARY ANSWER: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. WHAT IS KNOWN ALREADY: First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). MAIN RESULTS AND THE ROLE OF CHANCE: Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints β = 0.017, 95% CI [0.009; 0.025], bifurcation points β = 0.012, 95% CI [0.006; 0.018], crossing points β = 0.017, 95% CI [0.008; 0.025], vessel points β = 0.01, 95% CI [0.002; 0.008], and total vascular length β = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV β = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV β = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV β = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV β -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV β = -48.604 95% CI [-74.246; -22.961])), all P-values &lt; 0.05. After stratification, the associations were observed in natural conceptions specifically.LIMITATION, REASONS FOR CAUTION: Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered at the Dutch Trial Register (NTR6854).</p

Entropy and information in neural spike trains: Progress on the sampling problem

The major problem in information theoretic analysis of neural responses and other biological data is the reliable estimation of entropy--like quantities from small samples. We apply a recently introduced Bayesian entropy estimator to synthetic data inspired by experiments, and to real experimental spike trains. The estimator performs admirably even very deep in the undersampled regime, where other techniques fail. This opens new possibilities for the information theoretic analysis of experiments, and may be of general interest as an example of learning from limited data.Comment: 7 pages, 4 figures; referee suggested changes, accepted versio

Vortex Motion Noise in Micrometre-Sized Thin Films of the Amorphous Nb0.7Ge0.3 Weak-Pinning Superconductor

We report high-resolution measurements of voltage (V) noise in the mixed state of micrometre-sized thin films of amorphous Nb0.7Ge0.3, which is a good representative of weak-pinning superconductors. There is a remarkable difference between the noise below and above the irreversibility field Birr. Below Birr, in the presence of measurable pinning, the noise at small applied currents resembles shot noise, and in the regime of flux flow at larger currents decreases with increasing voltage due to a progressive ordering of the vortex motion. At magnetic fields B between Birr and the upper critical field Bc2 flux flow is present already at vanishingly small currents. In this regime the noise scales with (1-B/Bc2)^2 V^2 and has a frequency (f) spectrum of 1/f type. We interpret this noise in terms of the properties of strongly driven depinned vortex systems at high vortex density.Comment: 8 pages, 5 figures, version accepted for publication in PR

Melting of two dimensional solids on disordered substrate

We study 2D solids with weak substrate disorder, using Coulomb gas renormalisation. The melting transition is found to be replaced by a sharp crossover between a high $T$ liquid with thermally induced dislocations, and a low $T$ glassy regime with disorder induced dislocations at scales larger than $\xi_{d}$ which we compute ($\xi_{d}\gg R_{c}\sim R_{a}$, the Larkin and translational correlation lengths). We discuss experimental consequences, reminiscent of melting, such as size effects in vortex flow and AC response in superconducting films.Comment: 4 pages, uses RevTeX, Amssymb, multicol,eps

Patterned Irradiation of YBa_2Cu_3O_(7-x) Thin Films

We present a new experiment on YBa_2Cu_3O_{7-x} (YBCO) thin films using spatially resolved heavy ion irradiation. Structures consisting of a periodic array of strong and weak pinning channels were created with the help of metal masks. The channels formed an angle of +/-45 Deg with respect to the symmetry axis of the photolithographically patterned structures. Investigations of the anisotropic transport properties of these structures were performed. We found striking resemblance to guided vortex motion as it was observed in YBCO single crystals containing an array of unidirected twin boundaries. The use of two additional test bridges allowed to determine in parallel the resistivities of the irradiated and unirradiated parts as well as the respective current-voltage characteristics. These measurements provided the input parameters for a numerical simulation of the potential distribution of the Hall patterning. In contrast to the unidirected twin boundaries in our experiment both strong and weak pinning regions are spatially extended. The interfaces between unirradiated and irradiated regions therefore form a Bose-glass contact. The experimentally observed magnetic field dependence of the transverse voltage vanishes faster than expected from the numerical simulation and we interpret this as a hydrodynamical interaction between a Bose-glass phase and a vortex liquid.Comment: 7 pages, 8 Eps figures included. Submitted to PR

How Gibbs distributions may naturally arise from synaptic adaptation mechanisms. A model-based argumentation

This paper addresses two questions in the context of neuronal networks dynamics, using methods from dynamical systems theory and statistical physics: (i) How to characterize the statistical properties of sequences of action potentials ("spike trains") produced by neuronal networks ? and; (ii) what are the effects of synaptic plasticity on these statistics ? We introduce a framework in which spike trains are associated to a coding of membrane potential trajectories, and actually, constitute a symbolic coding in important explicit examples (the so-called gIF models). On this basis, we use the thermodynamic formalism from ergodic theory to show how Gibbs distributions are natural probability measures to describe the statistics of spike trains, given the empirical averages of prescribed quantities. As a second result, we show that Gibbs distributions naturally arise when considering "slow" synaptic plasticity rules where the characteristic time for synapse adaptation is quite longer than the characteristic time for neurons dynamics.Comment: 39 pages, 3 figure

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Clinical significance of VEGF-A, -C and -D expression in esophageal malignancies

Vascular endothelial growth factors ( VEGF)- A, - C and - D are members of the proangiogenic VEGF family of glycoproteins. VEGF-A is known to be the most important angiogenic factor under physiological and pathological conditions, while VEGF-C and VEGF-D are implicated in the development and sprouting of lymphatic vessels, so called lymphangiogenesis. Local tumor progression, lymph node metastases and hematogenous tumor spread are important prognostic factors for esophageal carcinoma ( EC), one of the most lethal malignancies throughout the world. We found solid evidence in the literature that VEGF expression contributes to tumor angiogenesis, tumor progression and lymph node metastasis in esophageal squamous cell carcinoma ( SCC), and many authors could show a prognostic value for VEGF-assessment. In adenocarcinoma (AC) of the esophagus angiogenic properties are acquired in early stages, particularly in precancerous lesions like Barrett's dysplasia. However, VEGF expression fails to give prognostic information in AC of the esophagus. VEGF-C and VEGF-D were detected in SCC and dysplastic lesions, but not in normal mucosa of the esophagus. VEGF-C expression might be associated with lymphatic tumor invasion, lymph node metastases and advanced disease in esophageal SCC and AC. Therapeutic interference with VEGF signaling may prove to be a promising way of anti-angiogenic co-treatment in esophageal carcinoma. However, concrete clinical data are still pending

Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter

Altres ajuts: Dutch Organisation for Scientifc Research, 400-07-213, 400-05-096, 400-07-2013MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a lower transcriptional efficiency compared to individuals who are homozygous for the l-allele ('l-group'). The present study aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood effects. Four placebo-controlled, within-subject studies were pooled, including in total 63 polydrug ecstasy users (N = 48; N = 15) receiving MDMA 75 mg and placebo on two test days, separated by minimally 7 days. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced -independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l-group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l-group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l-allele showing this beneficial effect