Detection of delirium by family members in the intensive care unit: Translation, Cross-Cultural adaptation and validation of the Family Confusion Assessment Method for the German-Speaking area

Aim: The aim of this study was the translation, cross-cultural adaptation and validation of the Family Confusion Assessment Method in critically ill patients. Background: Delirium is a frequently unrecognized disorder in critically ill patients. Visiting family members might be the first to notice subtle changes in a patient's cognition and behaviour. The Family Confusion Assessment Method was developed to detect delirium by family members, but has not been available for the German-speaking area yet. Design: A prospective validation study was conducted between January 2020 and October 2020. Methods: The Family Confusion Assessment Method was translated into German according to the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes. Subsequently, we compared the Family Confusion Assessment Method with the Confusion Assessment Method for the Intensive Care Unit in critically ill patients and their family members in a medical intensive care unit in Germany. Results: We included 50 dyads of critically ill patients and their family members. The prevalence of delirium measured by Confusion Assessment Method for the Intensive Care Unit was 44%. Cohen's kappa coefficient was 0.84. The German Family Confusion Assessment Method had a high sensitivity of 95.5% and specificity of 89.3%. The positive predictive value and negative predictive value were 87.5% and 96.2% respectively. Conclusions: These findings suggest that the German Family Confusion Assessment Method is an accurate assessment tool for delirium detection in the intensive care unit by family members. Furthermore, the results indicate that family members may identify delirium by the Family Confusion Assessment Method without prior training. Impact: Collaborating medical staff with patients' family members to detect delirium in the intensive care unit may lead to early recognition of delirium. Keywords: Family Confusion Assessment Method; delirium; family members; intensive care unit; nurses; validation study

Growth patterns in Onychophora (velvet worms): lack of a localised posterior proliferation zone

<p>Abstract</p> <p>Background</p> <p>During embryonic development of segmented animals, body segments are thought to arise from the so-called "posterior growth zone" and the occurrence of this "zone" has been used to support the homology of segmentation between arthropods, annelids, and vertebrates. However, the term "posterior growth zone" is used ambiguously in the literature, mostly referring to a region of increased proliferation at the posterior end of the embryo. To determine whether such a localised posterior proliferation zone is an ancestral feature of Panarthropoda (Onychophora + Tardigrada + Arthropoda), we examined cell division patterns in embryos of Onychophora.</p> <p>Results</p> <p>Using in vivo incorporation of the DNA replication marker BrdU (5-bromo-2'-deoxyuridine) and anti-phospho-histone H3 immunolabelling, we found that a localised posterior region of proliferating cells does not occur at any developmental stage in onychophoran embryos. This contrasts with a localised pattern of cell divisions at the posterior end of annelid embryos, which we used as a positive control. Based on our data, we present a mathematical model, which challenges the paradigm that a localised posterior proliferation zone is necessary for segment patterning in short germ developing arthropods.</p> <p>Conclusions</p> <p>Our findings suggest that a posterior proliferation zone was absent in the last common ancestor of Onychophora and Arthropoda. By comparing our data from Onychophora with those from annelids, arthropods, and chordates, we suggest that the occurrence of a "posterior growth zone" currently cannot be used to support the homology of segmentation between these three animal groups.</p

From hybridomas to a robust microalgal-based production platform: molecular design of a diatom secreting monoclonal antibodies directed against the Marburg virus nucleoprotein

Background: The ideal protein expression system should provide recombinant proteins in high quality and quantity involving low production costs only. However, especially for complex therapeutic proteins like monoclonal antibodies many challenges remain to meet this goal and up to now production of monoclonal antibodies is very costly and delicate. Particularly, emerging disease outbreaks like Ebola virus in Western Africa in 2014–2016 make it necessary to reevaluate existing production platforms and develop robust and cheap alternatives that are easy to handle. Results: In this study, we engineered the microalga Phaeodactylum tricornutum to produce monoclonal IgG antibodies against the nucleoprotein of Marburg virus, a close relative of Ebola virus causing severe hemorrhagic fever with high fatality rates in humans. Sequences for both chains of a mouse IgG antibody were retrieved from a murine hybridoma cell line and implemented in the microalgal system. Fully assembled antibodies were shown to be secreted by the alga and antibodies were proven to be functional in western blot, ELISA as well as IFA studies just like the original hybridoma produced IgG. Furthermore, synthetic variants with constant regions of a rabbit IgG and human IgG with optimized codon usage were produced and characterized. Conclusions: This study highlights the potential of microalgae as robust and low cost expression platform for monoclonal antibodies secreting IgG antibodies directly into the culture medium. Microalgae possess rapid growth rates, need basically only water, air and sunlight for cultivation and are very easy to handle

Macrophage cholesterol efflux correlates with lipoprotein subclass distribution and risk of obstructive coronary artery disease in patients undergoing coronary angiography

<p>Abstract</p> <p>Background</p> <p>Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in142 normolipidemic subjects undergoing coronary angiography.</p> <p>Methods</p> <p>Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography.</p> <p>Results</p> <p>Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concntration of larger and triglyceride rich particles (VLDL, chylomicrons). Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02).</p> <p>Conclusion</p> <p>Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.</p

Machine Learning Using a Single-Lead ECG to Identify Patients With Atrial Fibrillation-Induced Heart Failure

AIMS: Atrial fibrillation (AF) and heart failure often co-exist. Early identification of AF patients at risk for AF-induced heart failure (AF-HF) is desirable to reduce both morbidity and mortality as well as health care costs. We aimed to leverage the characteristics of beat-to-beat-patterns in AF to prospectively discriminate AF patients with and without AF-HF. METHODS: A dataset of 10,234 5-min length RR-interval time series derived from 26 AF-HF patients and 26 control patients was extracted from single-lead Holter-ECGs. A total of 14 features were extracted, and the most informative features were selected. Then, a decision tree classifier with 5-fold cross-validation was trained, validated, and tested on the dataset randomly split. The derived algorithm was then tested on 2,261 5-min segments from six AF-HF and six control patients and validated for various time segments. RESULTS: The algorithm based on the spectral entropy of the RR-intervals, the mean value of the relative RR-interval, and the root mean square of successive differences of the relative RR-interval yielded an accuracy of 73.5%, specificity of 91.4%, sensitivity of 64.7%, and PPV of 87.0% to correctly stratify segments to AF-HF. Considering the majority vote of the segments of each patient, 10/12 patients (83.33%) were correctly classified. CONCLUSION: Beat-to-beat-analysis using a machine learning classifier identifies patients with AF-induced heart failure with clinically relevant diagnostic properties. Application of this algorithm in routine care may improve early identification of patients at risk for AF-induced cardiomyopathy and improve the yield of targeted clinical follow-up

Validating left atrial fractionation and low-voltage substrate during atrial fibrillation and sinus rhythm-A high-density mapping study in persistent atrial fibrillation

Altres ajuts: Deutsche Herzstiftung (German Heart Foundation).Background: Low-voltage-substrate (LVS)-guided ablation for persistent atrial fibrillation (AF) has been described either in sinus rhythm (SR) or AF. Prolonged fractionated potentials (PFPs) may represent arrhythmogenic slow conduction substrate and potentially co-localize with LVS. We assess the spatial correlation of PFP identified in AF (PFP-AF) to those mapped in SR (PFP-SR). We further report the relationship between LVS and PFPs when mapped in AF or SR. Materials and methods: Thirty-eight patients with ablation naïve persistent AF underwent left atrial (LA) high-density mapping in AF and SR prior to catheter ablation. Areas presenting PFP-AF and PFP-SR were annotated during mapping on the LA geometry. Low-voltage areas (LVA) were quantified using a bipolar threshold of 0.5 mV during both AF and SR mapping. Concordance of fractionated potentials (CFP) (defined as the presence of PFPs in both rhythms within a radius of 6 mm) was quantified. Spatial distribution and correlation of PFP and CFP with LVA were assessed. The predictors for CFP were determined. Results: PFPs displayed low voltages both during AF (median 0.30 mV (Q1-Q3: 0.20-0.50 mV) and SR (median 0.35 mV (Q1-Q3: 0.20-0.56 mV). The duration of PFP-SR was measured at 61 ms (Q1-Q3: 51-76 ms). During SR, most PFP-SRs (89.4 and 97.2%) were located within LVA (40%), followed by posterior LA (>20%) and septal LA (>15%). The extent of LVA 80%) fractionation concordance in AF and SR. Conclusion: Substrate mapping in SR vs. AF reveals smaller areas of low voltage and fewer sites with PFP. PFP-SR are located within low-voltage areas in SR. There is a high degree of spatial agreement (80%) between PFP-AF and PFP-SR in patients with moderate LVA in SR (>16% of LA surface). These findings should be considered when substrate-based ablation strategies are applied in patients with the left atrial low-voltage substrate with recurrent persistent AF

Parameter likelihood of intrinsic ellipticity correlations

Subject of this paper are the statistical properties of ellipticity alignments between galaxies evoked by their coupled angular momenta. Starting from physical angular momentum models, we bridge the gap towards ellipticity correlations, ellipticity spectra and derived quantities such as aperture moments, comparing the intrinsic signals with those generated by gravitational lensing, with the projected galaxy sample of EUCLID in mind. We investigate the dependence of intrinsic ellipticity correlations on cosmological parameters and show that intrinsic ellipticity correlations give rise to non-Gaussian likelihoods as a result of nonlinear functional dependencies. Comparing intrinsic ellipticity spectra to weak lensing spectra we quantify the magnitude of their contaminating effect on the estimation of cosmological parameters and find that biases on dark energy parameters are very small in an angular-momentum based model in contrast to the linear alignment model commonly used. Finally, we quantify whether intrinsic ellipticities can be measured in the presence of the much stronger weak lensing induced ellipticity correlations, if prior knowledge on a cosmological model is assumed.Comment: 14 pages, 8 figures, submitted to MNRA

Towards a framework for attention cueing in instructional animations: Guidelines for research and design

This paper examines the transferability of successful cueing approaches from text and static visualization research to animations. Theories of visual attention and learning as well as empirical evidence for the instructional effectiveness of attention cueing are reviewed and, based on Mayer’s theory of multimedia learning, a framework was developed for classifying three functions for cueing: (1) selection—cues guide attention to specific locations, (2) organization—cues emphasize structure, and (3) integration—cues explicate relations between and within elements. The framework was used to structure the discussion of studies on cueing in animations. It is concluded that attentional cues may facilitate the selection of information in animations and sometimes improve learning, whereas organizational and relational cueing requires more consideration on how to enhance understanding. Consequently, it is suggested to develop cues that work in animations rather than borrowing effective cues from static representations. Guidelines for future research on attention cueing in animations are presented

Foundations for Open Scholarship Strategy Development, Version 2.1 [Pre-print]

This document aims to agree on a broad, international strategy for the implementation of open scholarship that meets the needs of different national and regional communities but works globally. Scholarly research can be idealised as an inspirational process for advancing our collective knowledge to the benefit of all humankind. However, current research practices often struggle with a range of tensions, in part due to the fact that this collective (or “commons”) ideal conflicts with the competitive system in which most scholars work, and in part because much of the infrastructure of the scholarly world is becoming largely digital. What is broadly termed as Open Scholarship is an attempt to realign modern research practices with this ideal. We do not propose a definition of Open Scholarship, but recognise that it is a holistic term that encompasses many disciplines, practices, and principles, sometimes also referred to as Open Science or Open Research. We choose the term Open Scholarship to be more inclusive of these other terms. When we refer to science in this document, we do so historically and use it as shorthand for more general scholarship. The purpose of this document is to provide a concise analysis of where the global Open Scholarship movement currently stands: what the common threads and strengths are, where the greatest opportunities and challenges lie, and how we can more effectively work together as a global community to recognise and address the top strategic priorities. This document was inspired by the Foundations for OER Strategy Development and work in the FORCE11 Scholarly Commons Working Group, and developed by an open contribution working group. Our hope is that this document will serve as a foundational resource for continuing discussions and initiatives about implementing effective strategies to help streamline the integration of Open Scholarship practices into a modern, digital research culture. Through this, we hope to extend the reach and impact of Open Scholarship into a global context, making sure that it is truly open for all. We also hope that this document will evolve as the conversations around Open Scholarship progress, and help to provide useful insight for both global co-ordination and local action. We believe this is a step forward in making Open Scholarship the norm. Ultimately, we expect the impact of widespread adoption of Open Scholarship to be diverse. We expect novel research practices to accelerate the pace of innovation, and therefore stimulate critical industries around the world. We could also expect to see an increase in public trust of science and scholarship, as transparency becomes more normative. As such, we expect interest in Open Scholarship to increase at multiple levels, due to its inherent influence on society and global economics

Cross-sectional associations between occupational factors and musculoskeletal pain in women teachers, nurses and sonographers

A. Technical measurements of the physical workload. (DOCX 18 kb