Competing risk models in early warning systems for in-hospital deterioration: the role of missing data imputation

Early Warning Systems (EWS) are useful and very important tools for evaluating the health deteriorating of hospitalised patients, using vital signs (such as heart rate, temperature, etc.) as the main input, based on electronic health records (EHR) which most of the time result in sparse data sets with high rates of missing data. In this work, we aim to study the effect of different imputation techniques on time-to-event (survival) models. For each case we have patient's sex and age, as well as longitudinal data along the hospitalisation for 7 vital signs (temperature, systolic and diastolic pressure, heart and respiratory rates, oxygen saturation and neurological state). We summarise these longitudinal data with the following central tendency, order and dispersion statistics: maximum, minimum, first observation, last observation, mean, standard deviation, average variance percentage and average derivative, transforming the original variables into a cross-sectional higher dimensional space, that still having missing data problems. Each hospitalisation has two possible final states: clinical deterioration or favourable discharge. Here, we model the time-to-event with competitive risk models taking into account the covariates. In the Galdakao-Usansolo University Hospital (Basque Country, Spain), a total of 19.602 hospitalisations (lengths of stay at least 24 hours) were collected during the year 2019, of which 852 (4.35\%) resulted in deterioration. These data correspond to 55.8\% of males and 44.2\% of females. We are using a set of imputation methods, such as central tendency statistics (mean and mode), Multiple Imputation by Chained Equations (MICE), Non-Linear Principal Components Analysis (NLPCA) and Random Forest. We evaluate the performances of the imputation methods described before, via root mean square error and conclude the pros and cons of using each one in medical practice. Then, we use Fine and Gray's competitive risk models and the cause-specific Cox proportional hazard regression to model the time-to-event as a function of imputed summarised data. Finally, we evaluate these models employing the traditional and time-dependent area under the ROC curve, for horizon times of 24, 48, 72, 96 and 120 hospitalisation hours

Competing risk modelling for in-hospital length of stay

In this study, we propose a framework for analysing in-hospital patient data from electronic health records. We transform longitudinal sparse vital signs measurements into cross-sectional data via descriptive statistics, imputing missing values, and evaluating variables strongly associated with time to mutually exclusive events (favourable medical discharge or deterioration). We employ competing risk and random survival forest techniques to predict patients’ length of stay and evaluate models’ performance via Brier score

Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health

Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis

Hematopoyesis heterotópica en anillos osificados de la tráquea de gallinas ponedoras afectadas con síndrome respiratorio crónico

En un estudio aleatorizado realizado en Cuba y en gallinas ponedoras y sus reemplazos afectadaspor síndrome respiratorio crónico (SRC), se muestrearon los órganos del sistema respiratorio de 65 gallinas,48 reemplazos y 30 sin alteraciones clínica aparentes. Las muestras fueron procesadas por histología convencional. Como hallazgo no esperado se observó la osificación del cartílago hialino de la tráquea (OCHT) y la presencia de medula ósea en los núcleos osificados. Esto fue confirmado por la tinción de Giemsa donde se pudo identificar células mieloblásticas y eritroblásticas. Dada la relación que existe entre la insuficiencia ventilatoria y la OCHT con hematopoyesis heterotópica en ambas categorías, se pueden establecer los siguientes mecanismos hipotéticos: Las aves pudieron establecer una adaptación de la Hb a la hipoxia crónica a la formación de hematopoyesis en la OCHT, como mecanismo compensatorio ante la hipoxia crónica causada por la insuficiencia ventilatoria, además existe una estrecha relación entre los osteoblastos (OCHT) y la hematopoyesis heterotópica

Nonuniversality of front fluctuations for compact colonies of nonmotile bacteria

The front of a compact bacterial colony growing on a Petri dish is a paradigmatic instance of non-equilibrium fluctuations in the celebrated Eden, or Kardar-Parisi-Zhang (KPZ), universality class. While in many experiments the scaling exponents crucially differ from the expected KPZ values, the source of this disagreement has remained poorly understood. We have performed growth experiments with B. subtilis 168 and E. coli ATCC 25922 under conditions leading to compact colonies in the classically alleged Eden regime, where individual motility is suppressed. Non-KPZ scaling is indeed observed for all accessible times, KPZ asymptotics being ruled out for our experiments due to the monotonic increase of front branching with time. Simulations of an effective model suggest the occurrence of transient nonuniversal scaling due to diffusive morphological instabilities, agreeing with expectations from detailed models of the relevant biological reaction-diffusion processes.This work has been supported by Ministerio de Economía y Competitividad, Agencia Estatal de Investigación, and Fondo Europeo de Desarrollo Regional (Spain and European Union) through Grants No. FIS2015- 66020-C2-1-P, FIS2015-69167-C2-1-P, FIS2015-73337-JIN, and BIO2016-79618-R, and by Comunidad Autónoma de Madrid (Spain) Grant No. NANOAVANSENS S2013/MIT302

Nonuniversality of front fluctuations for compact colonies of nonmotile bacteria

The front of a compact bacterial colony growing on a Petri dish is a paradigmatic instance of non-equilibrium f luctuations in the celebrated Eden, or Kardar-Parisi-Zhang (KPZ), universality class. While in many experiments the scaling exponents crucially differ from the expected KPZ values, the source of this disagreement has remained poorly understood. We have performed growth experiments with B. subtilis 168 and E. coli ATCC 25922 under conditions leading to compact colonies in the classically alleged Eden regime, where individual motility is suppressed. Non-KPZ scaling is indeed observed for all accessible times, KPZ asymptotics being ruled out for our experiments due to the monotonic increase of front branching with time. Simulations of an effective model suggest the occurrence of transient nonuniversal scaling due to diffusive morphological instabilities, agreeing with expectations from detailed models of the relevant biological reaction-diffusion processe

A mid-infrared view of the inner parsecs of the Seyfert galaxy Mrk 1066 using CanariCam/GTC

We present mid-infrared (MIR) imaging and spectroscopic data of the Seyfert 2 galaxy Mrk 1066 obtained with CanariCam (CC) on the 10.4-m Gran Telescopio CANARIAS (GTC). The galaxy was observed in imaging mode with an angular resolution of 0.24 arcsec (54 pc) in the Si-2 filter (8.7 μm). The image reveals a series of star-forming knots within the central ∼400 pc, after subtracting the dominant active galactic nucleus (AGN) component. We also subtracted this AGN unresolved component from the 8–13 μm spectra of the knots and the nucleus, and measured equivalent widths (EWs) of the 11.3 μm polycyclic aromatic hydrocarbon (PAH) feature which are typical of pure starburst galaxies. This EW is larger in the nucleus than in the knots, confirming that, at least in the case of Mrk 1066, the AGN dilutes, rather than destroys, the molecules responsible for the 11.3 μm PAH emission. By comparing the nuclear GTC/CC spectrum with the Spitzer/Infrared Spectrograph (IRS) spectrum of the galaxy, we find that the AGN component that dominates the continuum emission at λ < 15 μm on scales of ∼60 pc (90–100 per cent) decreases to 35–50 per cent when the emission of the central ∼830 pc is considered. On the other hand, the AGN contribution dominates the 15–25 μm emission (75 per cent) on the scales probed by Spitzer/IRS. We reproduced the nuclear infrared emission of the galaxy with clumpy torus models, and derived a torus gas mass of 2 × 10^5  M_⊙, contained in a clumpy structure of ∼2 pc radius and with a column density compatible with Mrk 1066 being a Compton-thick candidate, in agreement with X-ray observations. We find a good match between the MIR morphology of Mrk 1066 and the extended Paβ, Brγ and [O iii] λ5007 emission. This coincidence implies that the 8.7 μm emission is probing star formation, dust in the narrow-line region and the oval structure previously detected in the near-infrared. On the other hand, the Chandra soft X-ray morphology does not match any of the previous, contrary to what it is generally assumed for Seyfert galaxies. A thermal origin for the soft X-ray emission, rather than AGN photoionization, is suggested by the different data analysed here

Solar energetic electron events measured by MESSENGER and Solar Orbiter. Peak intensity and energy spectrum radial dependences: statistical analysis

Context/Aims: We present a list of 61 solar energetic electron (SEE) events measured by the MESSENGER mission and the radial dependences of the electron peak intensity and the peak-intensity energy spectrum. The analysis comprises the period from 2010 to 2015, when MESSENGER heliocentric distance varied between 0.31 and 0.47 au. We also show the radial dependencies for a shorter list of 12 SEE events measured in February and March 2022 by spacecraft near 1 au and by Solar Orbiter around its first close perihelion at 0.32 au. Results: Due to the elevated background intensity level of the particle instrument on board MESSENGER, the SEE events measured by this mission are necessarily large and intense; most of them accompanied by a CME-driven shock, being widespread in heliolongitude, and displaying relativistic ($\sim$1 MeV) electron intensity enhancements. The two main conclusions derived from the analysis of the large SEE events measured by MESSENGER, which are generally supported by Solar Orbiter's data results, are: (1) There is a wide variability in the radial dependence of the electron peak intensity between $\sim$0.3 au and $\sim$1 au, but the peak intensities of the energetic electrons decrease with radial distance from the Sun in 27 out of 28 events. On average and within the uncertainties, we find a radial dependence consistent with $R^{-3}$. (2) The electron spectral index found in the energy range around 200 keV ($\delta$200) of the backward-scattered population near 0.3 au measured by MESSENGER is harder in 19 out of 20 (15 out of 18) events by a median factor of $\sim$20% ($\sim$10%) when comparing to the anti-sunward propagating beam (backward-scattered population) near 1 au.Comment: 20 pages, 13 figure