Disease Progression Modeling and Prediction through Random Effect Gaussian Processes and Time Transformation

The development of statistical approaches for the joint modelling of the temporal changes of imaging, biochemical, and clinical biomarkers is of paramount importance for improving the understanding of neurodegenerative disorders, and for providing a reference for the prediction and quantification of the pathology in unseen individuals. Nonetheless, the use of disease progression models for probabilistic predictions still requires investigation, for example for accounting for missing observations in clinical data, and for accurate uncertainty quantification. We tackle this problem by proposing a novel Gaussian process-based method for the joint modeling of imaging and clinical biomarker progressions from time series of individual observations. The model is formulated to account for individual random effects and time reparameterization, allowing non-parametric estimates of the biomarker evolution, as well as high flexibility in specifying correlation structure, and time transformation models. Thanks to the Bayesian formulation, the model naturally accounts for missing data, and allows for uncertainty quantification in the estimate of evolutions, as well as for probabilistic prediction of disease staging in unseen patients. The experimental results show that the proposed model provides a biologically plausible description of the evolution of Alzheimer's pathology across the whole disease time-span as well as remarkable predictive performance when tested on a large clinical cohort with missing observations.Comment: 13 pages, 2 figure

Update on Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia

AbstractBronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway

Stereodivergent-at-Metal Synthesis of [60]Fullerene Hybrids

Chiral fullerene–metal hybrids with complete control over the four stereogenic centers, including the absolute configuration of the metal atom, have been synthesized for the first time. The stereochemistry of the four chiral centers formed during [60]fullerene functionalization is the result of both the chiral catalysts employed and the diastereoselective addition of the metal complexes used (iridium, rhodium, or ruthenium).DFT calculations underpin the observed configurational stability at the metal center, which does not undergo an epimerization process

Fullerenes for Catalysis: Metallofullerenes in Hydrogen Transfer Reactions

[60]Fullerene hybrids have succesfully been used as catalysts in hydrogen transfer reactions, namely ketones reduction and Nalkylation with alcoholes. Due to the poor solubility in polar solvent, these hybrids behave as homogeneous/heterogeneous catalysts that can be mechanically separated and reused for several times while the final products do not need chromatographic separation

Synthesis of modified fullerenes for oxygen reduction reactions

In the search for carbon based catalysts for Oxygen Reduction Reactions (ORR), two different classes of fullerene hybrids and metal free fullerene derivatives have been prepared by highly selective metal- and organo-catalyzed synthetic methods. They were included as both electron acceptors and catalysts in polymer-based photo-electrochemical cell,fully demonstrating electrocatalytic activity. Remarkably, the activity of the metal free fullerenes proved to be as high as that observed for metallofullerenes based on noble metals, and up to ten-fold higher than by using PCBM

Deep Inelastic Lepton Scattering in Nuclei at x > 1 and the Nucleon Spectral Function

The nuclear structure function F_2A(x) has been studied in the Bjorken limit for (l, l') scattering on nuclei in the region of x > 1 and was found to be very sensitive to the information contained in the nucleon spectral function in nuclei, particularly the correlations between momenta and energies in the region of large momenta. Calculations were done in a local density approximation using two different spectral functions for nuclear matter. Results are compared to those obtained for a spectral function which has been evaluated directly for the finite nucleus, ^{16}O, under consideration. For values of x around 1.5 and larger the quasiparticle contribution is negligible, thus stressing the sensitivity of the present reaction to the dynamical properties of nuclei beyond the shell model approach. Several approximations which are usually employed in studies of the EMC effect have been analyzed and their inaccuracy in this region is demonstrated. The results stress the fact that the nuclear structure function contains important information on nuclear dynamical correlations. Therefore further measurements of F_2A(x) in that region and for many nuclei would be most welcome.Comment: 24 pages, LaTeX, 11 PostScript figures, final version to appear in Nuclear Physics

Quasielastic Versus Inelastic and Deep Inelastic Lepton Scattering in Nuclei at x > 1

We have made a thorough investigation of the nuclear structure function W_2A in the region of 0.8 < x < 1.5 and Q^2 < 20 GeV^2, separating the quasielastic and inelastic plus deep inelastic contributions. The agreement with present experimental data is good giving support to the results for both channels. Predictions are made in yet unexplored regions of x and Q^2 to assert the weight of the quasielastic or inelastic channels. We find that at Q^2 < 4 GeV^2 the structure function is dominated by the quasielastic contributions for x < 1.5, while for values of Q^2 > 15 GeV^2 and the range of x studied the inelastic channels are over one order of magnitude bigger than the quasielastic one. The potential of the structure function at x > 1 as a source of information on nuclear correlations is stressed once more.Comment: 17 pages, LaTeX, 13 PostScript figures, final version to be published in Nuclear Physics

L-citrulline is protective in hyperoxic lung damage and improves matrix remodelling and alveolarization

Moderate hyperoxia alters alveolar and vascular lung morphogenesis. Nitric oxide (NO) and matrix metalloproteinases (MMP) have a crucial role in the homeostasis of the matrix and bronchoalveolar structure and may be regulated abnormally by exposure to hyperoxia. Disruption of vascular endothelial growth factor (VEGF)-NO signaling impairs vascular growth and contributes to hyperoxia-induced vascular disease in bronchopulmonary dysplasia (BPD). We hypothesize that L-citrulline, by raising the serum levels of L-arginine and enhancing endogenous NO synthesis, might attenuate hyperoxia-induced lung injury in an experimental model of BPD. Neonatal rats (1 day old) were exposed to 60% oxygen or room air for 14 days and administered L-citrulline or a vehicle (sham). Lung morphometry were performed; Serum was tested for arginine level; Matrix metalloproteinases2 (MMP2) gene expression, VEGF gene and protein expression and endothelial NO synthase (eNOS) protein expression were compared. Mean linear intercept was higher in the hyperoxia and sham groups when compared with the room air (RA) and L-citr+hyperoxia treated group (p&lt;0.02). Secondary crests number was higher in L-citrulline treated and RA when compared to hyperoxia and sham group (p&lt;0.02). L-Arginine level rose in the L-citrulline-treated group (p&lt;0.05). L-citrulline did not affect MMP2 gene expression, but it regulated the MMP2 active protein, which rose in bronchoalveolar lavage fluid (p&lt;0.05), presumably due to a post-transductional effect. Compared with RA controls, hyperoxia significantly decreased VEGF and eNOS protein expression. At the same time, an increased lung VEGF gene and protein expression (p&lt;0.05) were also seen in the rats treated with L-citrulline. We conclude that: (i) hyperoxia decreases growth and disrupts VEGF-NO signaling of lung; (ii) the main effects of L-citrulline are an increased serum level of arginine, as a promoter and a substrate of the nitric oxide synthase; and (ii) a better alveolar growth and matrix control than in hyperoxia-induced lung damage seems promising

Hierarchical Bayesian level set inversion

The level set approach has proven widely successful in the study of inverse problems for inter- faces, since its systematic development in the 1990s. Re- cently it has been employed in the context of Bayesian inversion, allowing for the quantification of uncertainty within the reconstruction of interfaces. However the Bayesian approach is very sensitive to the length and amplitude scales in the prior probabilistic model. This paper demonstrates how the scale-sensitivity can be cir- cumvented by means of a hierarchical approach, using a single scalar parameter. Together with careful con- sideration of the development of algorithms which en- code probability measure equivalences as the hierar- chical parameter is varied, this leads to well-defined Gibbs based MCMC methods found by alternating Metropolis-Hastings updates of the level set function and the hierarchical parameter. These methods demon- strably outperform non-hierarchical Bayesian level set methods