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

Changes of the Neutron Flux of the Nuclear Reactor Triga Mark III Since the Conversion from High to Low 235U Enrichment

The neutron flux of the Triga Mark III research reactor was studied using nuclear track detectors. The facility of the National Institute for Nuclear Research (ININ), operates with a new core load of 85 LEU 30/20 (Low Enriched Uranium) fuel elements. The reactor provides a neutron flux around 2 × 1012 n cm-2s-1 at the irradiation channel. In this channel, CR-39 (allyl diglycol policarbonate) Landauer® detectors were exposed to neutrons; the detectors were covered with a 3 mm acrylic sheet for (n, p) reaction. Results show a linear response between the reactor power in the range 0.1 - 7 kW, and the average nuclear track density with data reproducibility and relatively low uncertainty (±5%). The method is a simple technique, fast and reliable procedure to monitor the research reactor operating power levels

Testing behavioral interventions to optimize participation in a population-based colorectal cancer screening program in Catalonia

The aim of the study was to measure the effect of three cost-neutral behavioral interventions on participation compared to the standard invitation letter in a population-based colorectal cancer screening program in 2014. For that purpose, a four-arm randomized field trial was conducted among 5077 individuals aged 50 to 69 years. Over an 8-week period, each week was randomly allocated to the intervention or the control conditions. Individuals assigned to the intervention conditions additionally received a prompt to write down the date to pick up the screening test in a pharmacy. Two of the three intervention groups also included an additional paragraph in the invitation letter on either: 1) the high proportion of individuals participating regularly (social norms condition) or 2) the importance of regular participation (benefit condition). We measured screening participation before and after receiving a reminder letter six weeks after the screening invitation. An overall 8.0 percentage point increase in CRC screening was achieved as a direct result of receiving a reminder letter; however none of the intervention strategies influenced participation. The only significant difference was found for newly invited individuals. There, participation rates decreased from 34.9% to 24.2% when the invitation mailing mentioned the importance of regular participation (OR: 0.60; 95% CI: 0.38-0.95). While none of the intervention strategies improved participation rates we found that praising the benefit of regular screening may discourage individuals who have never been invited before as the continuous behavior may be perceived as a large request. Nevertheless, the reminder letter boosted participation rates independently of the intervention assigned

Higgs Scalars in the Minimal Non-minimal Supersymmetric Standard Model

We consider the simplest and most economic version among the proposed non-minimal supersymmetric models, in which the $\mu$-parameter is promoted to a singlet superfield, whose all self-couplings are absent from the renormalizable superpotential. Such a particularly simple form of the renormalizable superpotential may be enforced by discrete $R$-symmetries which are extended to the gravity-induced non-renormalizable operators as well. We show explicitly that within the supergravity-mediated supersymmetry-breaking scenario, the potentially dangerous divergent tadpoles associated with the presence of the gauge singlet first appear at loop levels higher than 5 and therefore do not destabilize the gauge hierarchy. The model provides a natural explanation for the origin of the $\mu$-term, without suffering from the visible axion or the cosmological domain-wall problem. Focusing on the Higgs sector of this minimal non-minimal supersymmetric standard model, we calculate its effective Higgs potential by integrating out the dominant quantum effects due to stop squarks. We then discuss the phenomenological implications of the Higgs scalars predicted by the theory for the present and future high-energy colliders. In particular, we find that our new minimal non-minimal supersymmetric model can naturally accommodate a relatively light charged Higgs boson, with a mass close to the present experimental lower bound.Comment: 63 pages (12 figures), extended versio

Genome-wide analysis of targets for post-transcriptional regulation by Rsm proteins in Pseudomonas putida

Post-transcriptional regulation is an important step in the control of bacterial gene expression in response to environmental and cellular signals. Pseudomonas putida KT2440 harbors three known members of the CsrA/RsmA family of post-transcriptional regulators: RsmA, RsmE and RsmI. We have carried out a global analysis to identify RNA sequences bound in vivo by each of these proteins. Affinity purification and sequencing of RNA molecules associated with Rsm proteins were used to discover direct binding targets, corresponding to 437 unique RNA molecules, 75 of them being common to the three proteins. Relevant targets include genes encoding proteins involved in signal transduction and regulation, metabolism, transport and secretion, stress responses, and the turnover of the intracellular second messenger c-di-GMP. To our knowledge, this is the first combined global analysis in a bacterium harboring three Rsm homologs. It offers a broad overview of the network of processes subjected to this type of regulation and opens the way to define what are the sequence and structure determinants that define common or differential recognition of specific RNA molecules by these proteins.This work was supported by grants BFU2013-43469-P, BFU2016-80122-P and PID2019-109372GB-I00 from the Plan Estatal de I+D+I (Agencia Estatal de Investigación, Spanish Ministry of Science and Innovation and FEDER funds). Funding from the Biotechnology and Biological Sciences Research Council, United Kingdom (BB/R012415/1), and the University of Malaya (FRGS grant FP022-2018A and HIR grant H-50001-00-A000027) are also gratefully acknowledged

Pmca-generated prions from the olfactory mucosa of patients with fatal familial insomnia cause prion disease in mice

Background: Fatal Familial Insomnia (FFI) is a genetic prion disease caused by the D178N mutation in the prion protein gene (PRNP) in coupling phase with methionine at PRNP 129. In 2017, we have shown that the olfactory mucosa (OM) collected from FFI patients contained traces of PrPSc detectable by Protein Misfolding Cyclic Amplification (PMCA). Methods: In this work, we have challenged PMCA-generated products obtained from OM and brain homogenate of FFI patients in BvPrP-Tg407 transgenic mice expressing the bank vole prion protein to test their ability to induce prion pathology. Results: All inoculated mice developed mild spongiform changes, astroglial activation, and PrPSc deposition mainly affecting the thalamus. However, their neuropathological alterations were different from those found in the brain of BvPrP-Tg407 mice injected with raw FFI brain homogenate. Conclusions: Although with some experimental constraints, we show that PrPSc present in OM of FFI patients is potentially infectious. Funding: This work was supported in part by the Italian Ministry of Health (GR-2013-02355724 and Ricerca Corrente), MJFF, ALZ, Alzheimer’s Research UK and the Weston Brain Institute (BAND2015), and Euronanomed III (SPEEDY) to FM; by the Spanish Ministerio de Economía y Competitividad (grant AGL2016-78054-R [AEI/FEDER, UE]) to JMT and JCE; AM-M was supported by a fellowship from the INIA (FPI-SGIT-2015-02)

Effects of Large CP-violating Soft Phases on Supersymmetric Electroweak Baryogenesis

We revisit the results of recent electroweak baryogenesis calculations and include all allowed large CP-violating supersymmetric phases. If the phases are large, the resulting baryon asymmetry can be considerably larger than the observed value $n_B/s \sim 4 \times 10^{-11}$. Much of the asymmetry must therefore be washed out, and we argue that the upper bound on the light Higgs mass is larger than the value reported in previous work.Comment: 15 pages, 3 figure

Mixing-induced CP violating sources for electroweak baryogenesis from a semiclassical approach

The effects of flavor mixing in electroweak baryogenesis is investigated in a generalized semiclassical WKB approach. Through calculating the nonadiabatic corrections to the particle currents it is shown that extra CP violation sources arise from the off-diagonal part of the equation of motion of particles moving inside the bubble wall. This type of mixing-induced source is of the first order in derivative expansion of the Higgs condensate, but is oscillation suppressed. The numerical importance of the mixing-induced source is discussed in the Minimal Supersymmetric Standard Model and compared with the source term induced by semiclassical force. It is found that in a large parameter space where oscillation suppression is not strong enough, the mixing-induced source can dominate over that from the semiclassical force.Comment: 19 pp, 2 figs, 1 table, some comments added, to appear in Eur.Phys.J.