Prediction of stillbirth from placental growth factor at 19-24 weeks

Objectives: To investigate whether measurement of maternal serum placental growth factor (PLGF) at 19-24 weeks’ gestation improves the performance of screening for stillbirths that is achieved by a combination of maternal factors, fetal biometry and uterine artery pulsatility index (UT-PI) and evaluate the performance of screening of this model for all stillbirths and those due to impaired placentation and unexplained or other causes. Methods: This was a prospective screening study of 70,003 singleton pregnancies including 268 stillbirths, carried out in two phases. The first phase, which included prospective measurements of UT-PI and fetal biometry were available in all cases. The second phase included prospective measurements of maternal serum PLGF which were available for 9,870 live births and 86 antepartum stillbirths. The values of PLGF obtained from this screening study were simulated in the remaining cases based on bivariate Gaussian distributions, defined by the mean and standard deviations. Multivariate logistic regression analysis was used to determine whether the addition of maternal serum PLGF improved the performance of screening that was achieved by a combination of maternal factors, fetal biometry and UT-PI. Results: Significant contribution to the prediction of stillbirths was provided by maternal factor derived a priori risk, MoM values of PLGF, UT-PI and fetal biometry Z-scores. A model combining these variables predicted 58% of all stillbirths and 84% of those due to impaired placentation, at false positive rate of 10%; within the impaired placentation group the detection rate of stillbirth at 37 weeks (97% vs 61%; p<0.01). Conclusions: A high proportion of stillbirths due to impaired placentation can be effectively identified in the second trimester of pregnancy

Graph-based simulated annealing: a hybrid approach to stochastic modeling of complex microstructures

A stochastic model is proposed for the efficient simulation of complex three-dimensional microstructures consisting of two different phases. The model is based on a hybrid approach, where in a first step a graph model is developed using ideas from stochastic geometry. Subsequently, the microstructure model is built by applying simulated annealing to the graph model. As an example of application, the model is fitted to a tomographic image describing the microstructure of electrodes in Li-ion batteries. The goodness of model fit is validated by comparing morphological characteristics of experimental and simulated data

Multiwavelength Studies of Young OB Associations

We discuss how contemporary multiwavelength observations of young OB-dominated clusters address long-standing astrophysical questions: Do clusters form rapidly or slowly with an age spread? When do clusters expand and disperse to constitute the field star population? Do rich clusters form by amalgamation of smaller subclusters? What is the pattern and duration of cluster formation in massive star forming regions (MSFRs)? Past observational difficulties in obtaining good stellar censuses of MSFRs have been alleviated in recent studies that combine X-ray and infrared surveys to obtain rich, though still incomplete, censuses of young stars in MSFRs. We describe here one of these efforts, the MYStIX project, that produced a catalog of 31,784 probable members of 20 MSFRs. We find that age spread within clusters are real in the sense that the stars in the core formed after the cluster halo. Cluster expansion is seen in the ensemble of (sub)clusters, and older dispersing populations are found across MSFRs. Direct evidence for subcluster merging is still unconvincing. Long-lived, asynchronous star formation is pervasive across MSFRs.Comment: 22 pages, 9 figures. To appear in "The Origin of Stellar Clusters", edited by Steven Stahler, Springer, 2017, in pres

Spatial point process theory

No abstract

Analysis of Sample Correlations for Monte Carlo Rendering

Modern physically based rendering techniques critically depend on approximating integrals of high dimensional functions representing radiant light energy. Monte Carlo based integrators are the choice for complex scenes and effects. These integrators work by sampling the integrand at sample point locations. The distribution of these sample points determines convergence rates and noise in the final renderings. The characteristics of such distributions can be uniquely represented in terms of correlations of sampling point locations. Hence, it is essential to study these correlations to understand and adapt sample distributions for low error in integral approximation. In this work, we aim at providing a comprehensive and accessible overview of the techniques developed over the last decades to analyze such correlations, relate them to error in integrators, and understand when and how to use existing sampling algorithms for effective rendering workflows.publishe

Reconstructing the reproductive mode of an Ediacaran macro-organism.

Enigmatic macrofossils of late Ediacaran age (580-541 million years ago) provide the oldest known record of diverse complex organisms on Earth, lying between the microbially dominated ecosystems of the Proterozoic and the Cambrian emergence of the modern biosphere. Among the oldest and most enigmatic of these macrofossils are the Rangeomorpha, a group characterized by modular, self-similar branching and a sessile benthic habit. Localized occurrences of large in situ fossilized rangeomorph populations allow fundamental aspects of their biology to be resolved using spatial point process techniques. Here we use such techniques to identify recurrent clustering patterns in the rangeomorph Fractofusus, revealing a complex life history of multigenerational, stolon-like asexual reproduction, interspersed with dispersal by waterborne propagules. Ecologically, such a habit would have allowed both for the rapid colonization of a localized area and for transport to new, previously uncolonized areas. The capacity of Fractofusus to derive adult morphology by two distinct reproductive modes documents the sophistication of its underlying developmental biology.This work has been supported by the Natural Environment Research Council [grant numbers NE/I005927/1 to C.G.K., NE/J5000045/1 to J.J.M., NE/L011409/1 to A.G.L. and NE/G523539/1 to E.G.M.], and a Henslow Junior Research Fellowship from Cambridge Philosophical Society to A.G.L.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nature1464

Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes

Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils.We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the literature ([Ca2+]i 1 μM; F/F0 5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structureinduced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes

Lobe Specific Ca2+-Calmodulin Nano-Domain in Neuronal Spines: A Single Molecule Level Analysis

Calmodulin (CaM) is a ubiquitous Ca2+ buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca2+-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca2+-CaM-dependent enzymes: Ca2+/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca2+ and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca2+ ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca2+ and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca2+ signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca2+-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca2+ channels, and to the microscopic injection rate of Ca2+ ions. We also demonstrate that Ca2+ saturation takes place via two different pathways depending on the Ca2+ injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca2+ sensors that can differentially transduce Ca2+ influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca2+-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity