44 research outputs found

    A Complete Pipeline for Heart Rate Extraction from Infant ECGs

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    \ua9 2024 by the authors.Infant electrocardiograms (ECGs) and heart rates (HRs) are very useful biosignals for psychological research and clinical work, but can be hard to analyse properly, particularly longform (≄5 min) recordings taken in naturalistic environments. Infant HRs are typically much faster than adult HRs, and so some of the underlying frequency assumptions made about adult ECGs may not hold for infants. However, the bulk of publicly available ECG approaches focus on adult data. Here, existing open source ECG approaches are tested on infant datasets. The best-performing open source method is then modified to maximise its performance on infant data (e.g., including a 15 Hz high-pass filter, adding local peak correction). The HR signal is then subsequently analysed, developing an approach for cleaning data with separate sets of parameters for the analysis of cleaner and noisier HRs. A Signal Quality Index (SQI) for HR is also developed, providing insights into where a signal is recoverable and where it is not, allowing for more confidence in the analysis performed on naturalistic recordings. The tools developed and reported in this paper provide a base for the future analysis of infant ECGs and related biophysical characteristics. Of particular importance, the proposed solutions outlined here can be efficiently applied to real-world, large datasets

    Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer

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    Background: Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. Methods: In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Results: Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. Conclusion: This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    Assessing parallel gene histories in viral genomes

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    Background: The increasing abundance of sequence data has exacerbated a long known problem: gene trees and species trees for the same terminal taxa are often incongruent. Indeed, genes within a genome have not all followed the same evolutionary path due to events such as incomplete lineage sorting, horizontal gene transfer, gene duplication and deletion, or recombination. Considering conflicts between gene trees as an obstacle, numerous methods have been developed to deal with these incongruences and to reconstruct consensus evolutionary histories of species despite the heterogeneity in the history of their genes. However, inconsistencies can also be seen as a source of information about the specific evolutionary processes that have shaped genomes. Results: The goal of the approach here proposed is to exploit this conflicting information: we have compiled eleven variables describing phylogenetic relationships and evolutionary pressures and submitted them to dimensionality reduction techniques to identify genes with similar evolutionary histories. To illustrate the applicability of the method, we have chosen two viral datasets, namely papillomaviruses and Turnip mosaic virus (TuMV) isolates, largely dissimilar in genome, evolutionary distance and biology. Our method pinpoints viral genes with common evolutionary patterns. In the case of papillomaviruses, gene clusters match well our knowledge on viral biology and life cycle, illustrating the potential of our approach. For the less known TuMV, our results trigger new hypotheses about viral evolution and gene interaction. Conclusions: The approach here presented allows turning phylogenetic inconsistencies into evolutionary information, detecting gene assemblies with similar histories, and could be a powerful tool for comparative pathogenomics.IGB was funded by the disappeared Spanish Ministry for Science and Innovation (CGL2010-16713). Work in Valencia was supported by grant BFU2012-30805 from the Spanish Ministry of Economy and Competitiveness (MINECO) to SFE. BMC is the recipient of an IDIBELL PhD fellowship.Mengual-ChuliĂĄ, B.; Bedhomme, S.; Lafforgue, G.; Elena Fito, SF.; Bravo, IG. (2016). Assessing parallel gene histories in viral genomes. BMC Evolutionary Biology. 16:1-15. https://doi.org/10.1186/s12862-016-0605-4S11516Hess J, Goldman N. Addressing inter-gene heterogeneity in maximum likelihood phylogenomic analysis: Yeasts revisited. PLoS ONE. 2011;6:e22783.Salichos L, Rokas A. Inferring ancient divergences requires genes with strong phylogenetic signals. 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    Tomato (Solanum lycopersicum L.) in the service of biotechnology

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    A next-generation liquid xenon observatory for dark matter and neutrino physics

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    The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector

    Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

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    Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

    613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

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    Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture

    Barley starch

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    This thesis examined barley amylopectin structure and looked for correlations between the structure and physical properties of starch. The structure of amylopectin and gelatinisation and retrogradation of starch were studied in 10 different barley cultivars/breeding lines with differing genetic background. Amylopectin is built up of thousands of chains of glucose monomers, organised into clusters. The detailed fine structure of amylopectin was studied by isolating clusters of amylopectin and their building blocks, which are the tightly branched units building up the clusters. Barley cultivars/breeding lines possessing the amo1 mutation had fewer long chains of DP≄38 in amylopectin and more large building blocks. The structure of building blocks was rather conserved between the different barley cultivars/breeding lines studied and was categorized into different size groups. These different building blocks were shown to be randomly distributed in the amylopectin molecule. The C-chains in amylopectin can be of any length and are a category of chains different from the B-chains. The backbone in amylopectin consists of a special type of B-chains which, when cleaved by α-amylase, become chains of a similar type to C-chains. Gelatinisation and retrogradation (recrystallisation of gelatinised starch) of barley starch was studied by differential scanning calorimetry. The amo1 mutation resulted in a broader gelatinisation temperature range and a higher enthalpy of retrogradation. Other structural features were also found to influence the physical properties of starch. Small clusters and denser structure of the building blocks resulted in higher gelatinisation temperature. Fast retrogradation was observed in barley which had amylopectin with shorter chains and many large building blocks consisting of many chains. Amylopectin structure was also studied in developing barley kernels. Three barley cultivars/breeding lines were grown in a phytotron and kernels were harvested at 9, 12 and 24 days after flowering. The results showed that amylopectin synthesized at later stages of development had a more tightly branched structure. Expression of the enzymes involved in starch biosynthesis is also known to change during endosperm development
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