The Overlooked Potential of Generalized Linear Models in Astronomy - I: Binomial Regression

Revealing hidden patterns in astronomical data is often the path to fundamental scientific breakthroughs; meanwhile the complexity of scientific inquiry increases as more subtle relationships are sought. Contemporary data analysis problems often elude the capabilities of classical statistical techniques, suggesting the use of cutting edge statistical methods. In this light, astronomers have overlooked a whole family of statistical techniques for exploratory data analysis and robust regression, the so-called Generalized Linear Models (GLMs). In this paper -- the first in a series aimed at illustrating the power of these methods in astronomical applications -- we elucidate the potential of a particular class of GLMs for handling binary/binomial data, the so-called logit and probit regression techniques, from both a maximum likelihood and a Bayesian perspective. As a case in point, we present the use of these GLMs to explore the conditions of star formation activity and metal enrichment in primordial minihaloes from cosmological hydro-simulations including detailed chemistry, gas physics, and stellar feedback. We predict that for a dark mini-halo with metallicity $\approx 1.3 \times 10^{-4} Z_{\bigodot}$, an increase of $1.2 \times 10^{-2}$ in the gas molecular fraction, increases the probability of star formation occurrence by a factor of 75%. Finally, we highlight the use of receiver operating characteristic curves as a diagnostic for binary classifiers, and ultimately we use these to demonstrate the competitive predictive performance of GLMs against the popular technique of artificial neural networks.Comment: 20 pages, 10 figures, 3 tables, accepted for publication in Astronomy and Computin

3D High-Resolution Cardiac Segmentation Reconstruction From 2D Views Using Conditional Variational Autoencoders

Accurate segmentation of heart structures imaged by cardiac MR is key for the quantitative analysis of pathology. High-resolution 3D MR sequences enable whole-heart structural imaging but are time-consuming, expensive to acquire and they often require long breath holds that are not suitable for patients. Consequently, multiplanar breath-hold 2D cines sequences are standard practice but are disadvantaged by lack of whole-heart coverage and low through-plane resolution. To address this, we propose a conditional variational autoencoder architecture able to learn a generative model of 3D high-resolution left ventricular (LV) segmentations which is conditioned on three 2D LV segmentations of one short-axis and two long-axis images. By only employing these three 2D segmentations, our model can efficiently reconstruct the 3D high-resolution LV segmentation of a subject. When evaluated on 400 unseen healthy volunteers, our model yielded an average Dice score of 87.92 ± 0.15 and outperformed competing architectures (TL-net, Dice score = 82.60 ± 0.23, p = 2.2 · 10 -16 )

Explainable Anatomical Shape Analysis through Deep Hierarchical Generative Models

Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer's disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging

The history of chemical enrichment in the intracluster medium from cosmological simulations

The distribution of metals in the intracluster medium (ICM) of galaxy clusters provides valuable information on their formation and evolution, on the connection with the cosmic star formation and on the effects of different gas processes. By analysing a sample of simulated galaxy clusters, we study the chemical enrichment of the ICM, its evolution, and its relation with the physical processes included in the simulation and with the thermal properties of the core. These simulations, consisting of re-simulations of 29 Lagrangian regions performed with an upgraded version of the smoothed particle hydrodynamics (SPH) gadget-3 code, have been run including two different sets of baryonic physics: one accounts for radiative cooling, star formation, metal enrichment and supernova (SN) feedback, and the other one further includes the effects of feedback from active galactic nuclei (AGN). In agreement with observations, we find an anti-correlation between entropy and metallicity in cluster cores, and similar radial distributions of heavy-element abundances and abundance ratios out to large cluster-centric distances ( 3cR180). In the outskirts, namely outside of 3c0.2 R180, we find a remarkably homogeneous metallicity distribution, with almost flat profiles of the elements produced by either SNIa or SNII. We investigated the origin of this phenomenon and discovered that it is due to the widespread displacement of metal-rich gas by early (z > 2-3) AGN powerful bursts, acting on small high-redshift haloes. Our results also indicate that the intrinsic metallicity of the hot gas for this sample is on average consistent with no evolution between z = 2 and z = 0, across the entire radial range

Cosmological hydrodynamical simulations of galaxy clusters: X-ray scaling relations and their evolution

We analyse cosmological hydrodynamical simulations of galaxy clusters to study the X-ray scaling relations between total masses and observable quantities such as X-ray luminosity, gas mass, X-ray temperature, and $Y_{X}$. Three sets of simulations are performed with an improved version of the smoothed particle hydrodynamics GADGET-3 code. These consider the following: non-radiative gas, star formation and stellar feedback, and the addition of feedback by active galactic nuclei (AGN). We select clusters with $M_{500} > 10^{14} M_{\odot} E(z)^{-1}$, mimicking the typical selection of Sunyaev-Zeldovich samples. This permits to have a mass range large enough to enable robust fitting of the relations even at $z \sim 2$. The results of the analysis show a general agreement with observations. The values of the slope of the mass-gas mass and mass-temperature relations at $z=2$ are 10 per cent lower with respect to $z=0$ due to the applied mass selection, in the former case, and to the effect of early merger in the latter. We investigate the impact of the slope variation on the study of the evolution of the normalization. We conclude that cosmological studies through scaling relations should be limited to the redshift range $z=0-1$, where we find that the slope, the scatter, and the covariance matrix of the relations are stable. The scaling between mass and $Y_X$ is confirmed to be the most robust relation, being almost independent of the gas physics. At higher redshifts, the scaling relations are sensitive to the inclusion of AGNs which influences low-mass systems. The detailed study of these objects will be crucial to evaluate the AGN effect on the ICM.Comment: 24 pages, 11 figures, 5 tables, replaced to match accepted versio

Abnormal ECG Findings in Athletes: Clinical Evaluation and Considerations.

PURPOSE OF REVIEW: Pre-participation cardiovascular evaluation with electrocardiography is normal practice for most sporting bodies. Awareness about sudden cardiac death in athletes and recognizing how screening can help identify vulnerable athletes have empowered different sporting disciplines to invest in the wellbeing of their athletes. RECENT FINDINGS: Discerning physiological electrical alterations due to athletic training from those representing cardiac pathology may be challenging. The mode of investigation of affected athletes is dependent on the electrical anomaly and the disease(s) in question. This review will highlight specific pathological ECG patterns that warrant assessment and surveillance, together with an in-depth review of the recommended algorithm for evaluation

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Pressure of the hot gas in simulations of galaxy clusters

14siWe analyse the radial pressure profiles, the intracluster medium (ICM) clumping factor and the Sunyaev-Zel'dovich (SZ) scaling relations of a sample of simulated galaxy clusters and groups identified in a set of hydrodynamical simulations based on an updated version of the treepm-SPH GADGET-3 code. Three different sets of simulations are performed: the first assumes non-radiative physics, the others include, among other processes, active galactic nucleus (AGN) and/or stellar feedback. Our results are analysed as a function of redshift, ICM physics, cluster mass and cluster cool-coreness or dynamical state. In general, the mean pressure profiles obtained for our sample of groups and clusters show a good agreement with X-ray and SZ observations. Simulated cool-core (CC) and non-cool-core (NCC) clusters also show a good match with real data. We obtain in all cases a small (if any) redshift evolution of the pressure profiles of massive clusters, at least back to z = 1. We find that the clumpiness of gas density and pressure increases with the distance from the cluster centre and with the dynamical activity. The inclusion of AGN feedback in our simulations generates values for the gas clumping (√{C}_{ρ }˜ 1.2 at R200) in good agreement with recent observational estimates. The simulated YSZ-M scaling relations are in good accordance with several observed samples, especially for massive clusters. As for the scatter of these relations, we obtain a clear dependence on the cluster dynamical state, whereas this distinction is not so evident when looking at the subsamples of CC and NCC clusters.openopenPlanelles, S.; Fabjan, D.; Borgani, S.; Murante, G.; Rasia, E.; Biffi, V.; Truong, N.; Ragone-Figueroa, C.; Granato, G. L.; Dolag, K.; Pierpaoli, E.; Beck, A. M.; Steinborn, Lisa K.; Gaspari, M.Planelles, S.; Fabjan, D.; Borgani, Stefano; Murante, G.; Rasia, E.; Biffi, Veronica; Truong, N.; Ragone Figueroa, C.; Granato, G. L.; Dolag, K.; Pierpaoli, E.; Beck, A. M.; Steinborn, Lisa K.; Gaspari, M

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.<p></p> Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.<p></p> Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.<p></p> Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings