Assessment of fetal development by HRV and chaotic global techniques

Introduction: Fetal heart rate and its variability during the course of gestation have been extensively researched. The overall reduction in heart rate and increase in fetal HRV is associated with fetal growth and the increase in neural integration. The increased complexity of the demands on the cardiovascular system leads to more variation in the temporal course of the heart rate which has been shown to be refl ected in measures of complexity. The aim of this work was to investigate novel complexity measures with respect to their ability to quantify changes over gestational age in individual fetuses consistently and in a stable manner. Methods: We examined 215 fetal magnetocardiograms (FMCG), each of 5 min duration, in 11 fetuses during the second and third trimesters (at least 10 data sets per fetus). From the FMCG we determined the  etal RR beat durations. For each 5 min time-series of RR intervals we then calculated Shannon entropy, high spectral entropy, high spectral Detrended Fluctuation Analysis, spec ral Multi-Taper Method as well as the standard deviation and two commonly used complexity measures: Approximate Entropy and Sample Entropy. For each subject and HRV measure, we performed regression analysis with respect to ges tational age. The coeffi cient of determination R2 was used to es timate ‘goodness-of-fi t’, the slope of the regression indicated the strength of the individual dependency on gestational age. Results: We found that the new complexity measures do not outperform ApEn. Conclusion: This study has now rejected the hypothesis that the spectral complexity measures outperform those applied previously

Construction and testing of a novel host-range defective myxoma virus vaccine with the M063 gene inactivated that is non-permissive for replication in rabbit cells

Deletion of the M063 gene from myxoma virus produces a virus that is unable to replicate in rabbit cells in vitro or in live rabbits but can be propagated in non-rabbit cell lines. A targeted M063 deletion mutant was constructed in the attenuated Uriarra strain of myxoma virus and the ability of this virus to act as a safe, non-transmissible vaccine against myxomatosis was tested in outbred laboratory rabbits. Immunization with the M063 deletion vaccine provided good short-term protection against lethal challenge with virulent myxoma virus. Long-term protection was similar to reported results with heterologous live virus, with some rabbits protected but others succumbing to challenge. Replication-deficient poxvirus vaccines, like the Modified Vaccinia Virus Ankara (MVA) in man and the myxoma virus vaccine described here in rabbits, are very attractive from a safety perspective. Seasonal boosting would be predicted to provide long-term protection. Targeted host-range gene deletions could have potential for rapid development of poxvirus vaccines in general.This study was funded by the Pest Animal Control Cooperative Research Centre. Grant McFadden is an International Scholar of the Howard Hughes Medical Institute

Reply to comments on ‘On the steadiness of separating meandering currents’

The authors thank Nof et al. for their comments on the authors’ paper ‘‘On the steadiness of separating meandering currents.’’ The authors’ paper was motivated by a series of papers by Nof et al. Under a certain set of conditions (reduced gravity, steady state, no meridional velocity at outflow, and parallel outflow), Nof et al. showed that a separating and retroflecting frictionless current cannot be steady because of a momentum imbalance. The main conclusion of the authors’ paper was that they agree with the Nof et al. result that a momentum imbalance exists and extended the proof to all possible configurations of retroflecting currents, even including friction. The authors’ results point to a new mechanism for the generation of variability in the ocean that is not related to dynamical instability of the flow. The main claim in the comments is that the authors incorrectly argued in the appendix that the steadystate solutions presented by Nof et al. in several papers fulfill the extra constraint u2 5g9h. In the original paper, the authors showed that it follows from the geostrophic assumption stated implicitly in all these Nof et al. papers, because the flow is assumed to be parallel. Nof et al. now argue that the flow is only approximately geostrophic in all Nof et al. papers. The authors show in this reply that for steady weakly meandering outflows approximate geostrophy does lead to a momentum imbalance paradox as Nof et al. claim. However, for a steady strongly meandering outflow, approximate geostrophy is not enough and one has to use the method explored by van Leeuwen and De Ruijter to derive a momentum imbalance paradox

Evolution of European prostate cancer screening protocols and summary of ongoing trials

Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.</p

Evolution of European prostate cancer screening protocols and summary of ongoing trials

Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.</p

Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury

Marginal donor kidneys are more likely to develop ischemia-reperfusion injury (IRI), resulting in inferior long-term outcomes. Perfusion techniques are used to attenuate IRI and improve graft quality. However, machine perfusion is still in its infancy, and more research is required for optimal conditions and potential repairing therapies. Experimental machine perfusion using porcine kidneys is a great way to investigate transplant-related IRI, but these experiments are costly and time-consuming. Therefore, an intermediate model to study IRI would be of great value. We developed a precision-cut kidney slice (PCKS) model that resembles ischemia-reperfusion and provides opportunities for studying multiple interventions simultaneously. Porcine kidneys were procured from a local slaughterhouse, exposed to 30 min of warm ischemia, and cold preserved. Subsequently, PCKS were prepared and incubated under various conditions. Adenosine triphosphate (ATP) levels and histological tissue integrity were assessed for renal viability and injury. Slicing did not influence tissue viability, and PCKS remained viable up to 72 h incubation with significantly increased ATP levels. Hypothermic and normothermic incubation led to significantly higher ATP levels than baseline. William’s medium E supplemented with Ciprofloxacin (and Amphotericin-B) provided the most beneficial condition for incubation of porcine PCKS. The porcine PCKS model can be used for studying transplant IR

Approximate Langevin Monte Carlo with adaptation for Bayesian full-waveform inversion

In this work, we present a proof of concept for Bayesian full-waveform inversion (FWI) in 2-D. This is based on approximate Langevin Monte Carlo sampling with a gradient-based adaptation of the posterior distribution. We apply our method to the Marmousi model, and it reliably recovers important aspects of the posterior, including the statistical moments, and 1-D and 2-D marginals. Depending on the variations of seismic velocities, the posterior can be significantly non-Gaussian, which directly suggest that using a Hessian approximation for uncertainty quantification in FWI may not be sufficient

Bayesian uncertainty estimation for full waveform inversion: A numerical study

Full waveform inversion enables us to obtain high-resolution subsurface images. However, estimating the associated uncertainties is not trivial. Hessian-based method gives us an opportunity to assess the uncertainties around a given estimate based on the inverse of the Hessian, evaluated at that estimate. In this work we study various algorithms for extracting information from this inverse Hessian based on a low-rank approximation. In particular, we compare the Lanczos method to the randomized singular value decomposition. We demonstrate that the low-rank approximation may lead to a biased conclusion

State-of-the-art stochastic data assimilation methods for high-dimensional non-Gaussian problems

This paper compares several commonly used state-of-the-art ensemble-based data assimilation methods in a coherent mathematical notation. The study encompasses different methods that are applicable to high-dimensional geophysical systems, like ocean and atmosphere, and provide an uncertainty estimate. Most variants of Ensemble Kalman Filters, Particle Filters and second-order exact methods are discussed, including Gaussian Mixture Filters, while methods that require an adjoint model or a tangent linear formulation of the model are excluded. The detailed description of all the methods in a mathematically coherent way provides both novices and experienced researchers with a unique overview and new insight in the workings and relative advantages of each method, theoretically and algorithmically, even leading to new filters. Furthermore, the practical implementation details of all ensemble and particle filter methods are discussed to show similarities and differences in the filters aiding the users in what to use when. Finally, pseudo-codes are provided for all of the methods presented in this paper