Temporal graphs represent interactions between entities over the time. These interactions may be direct (a contact between two nodes at some time instant), or indirect, through sequences of contacts called temporal paths (journeys). Deciding whether an entity can reach another through a journey is useful for various applications in communication networks and epidemiology, among other fields. In this paper, we present a data structure that maintains temporal reachability information under the addition of new contacts. In contrast to previous works, the contacts can be inserted in an arbitrary order—in particular, non-chronologically—which corresponds to systems where the information is collected a posteriori (e.g., when trying to reconstruct contamination chains among people). The main component of our data structure is a generalization of transitive closure called timed transitive closure (TTC), which allows us to maintain reachability information relative to all nested time intervals, without storing all these intervals, nor the journeys themselves. Let n be the number of nodes and \(\tau\) be the number of timestamps in the lifetime of the temporal graph. Our data structure answers reachability queries regarding the existence of a journey from a given node to another within a given time interval in time \(O(\log \tau )\); it has a worst-case insertion time of \(O(n^2\log \tau )\); and it can reconstruct a valid journey that witnesses reachability in time \(O(k\log \tau )\), where \(k<n\) is the maximum number of contacts of this journey. Finally, the space complexity of our reachability data structure is \(O(n^2\tau )\), which remains within the worst-case size of the temporal graph itself.
Background The capacity to use data linkage and artificial intelligence to estimate and predict health indicators varies across European countries. However, the estimation of health indicators from linked administrative data is challenging due to several reasons such as variability in data sources and data collection methods resulting in reduced interoperability at various levels and timeliness, availability of a large number of variables, lack of skills and capacity to link and analyze big data. The main objective of this study is to develop the methodological guidelines calculating population-based health indicators to guide European countries using linked data and/or machine learning (ML) techniques with new methods. Method We have performed the following step-wise approach systematically to develop the methodological guidelines: i. Scientific literature review, ii. Identification of inspiring examples from European countries, and iii. Developing the checklist of guidelines contents. Results We have developed the methodological guidelines, which provide a systematic approach for studies using linked data and/or ML-techniques to produce population-based health indicators. These guidelines include a detailed checklist of the following items: rationale and objective of the study (i.e., research question), study design, linked data sources, study population/sample size, study outcomes, data preparation, data analysis (i.e., statistical techniques, sensitivity analysis and potential issues during data analysis) and study limitations. Conclusions This is the first study to develop the methodological guidelines for studies focused on population health using linked data and/or machine learning techniques. These guidelines would support researchers to adopt and develop a systematic approach for high-quality research methods. There is a need for high-quality research methodologies using more linked data and ML-techniques to develop a structured cross-disciplinary approach for improving the population health information and thereby the population health.
The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.
The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science–policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.
Context Understanding plant resilience and adaptation to drought is a major challenge in crop and forest sciences. Several methods have been developed to assess the vulnerability to xylem embolism. The in situ flow centrifuge (or cavitron) is the fastest technique allowing to characterise this trait for plants having vessel lengths shorter than the rotor size. Aims We present (i) a series of changes to the earlier cavitron design, aimed at improving the accuracy and speed of measurement through automated operations, and (ii) a new development through the design of a large diameter rotor expanding the range of species that can be measured. Methods Both hardware and software modifications to the original design have been developed. In order to avoid artefacts caused by cut open vessels, a centrifuge with a large rotor (1 m) has been developed, and vulnerability curves obtained with this new device were compared with those obtained using reference methods. Results The new set-up expands the range of conductance measurable with a cavitron and enables it to accurately determine the absolute value of conductivity even for species having very low hydraulic conductivity. The large rotor cavitron shows good agreement with the reference techniques for conifers and diffuse-porous species but also for ring-porous species having long vessels. Conclusion The set-up described in this manuscript provides a faster, safer and more accurate method to construct vulnerability curves, compared to the original cavitron design, and extends the measurement capabilities to new species that are difficult to measure to date. Key message Recent improvements to cavitron setup enable to measure xylem vulnerability curves for an expanded number of plant species, with longer vessels or lower hydraulic conductivity.
Here we present the ability of Nd ³⁺ -doped zinc-phosphate glasses to be shaped into rectangular core fibers. At first, the physico-chemical properties of the developed P 2 O 5 -based materials are investigated for different concentrations of neodymium oxide and core and cladding glass compositions are selected for further fiber development. A modified stack-and-draw technique is used to produce multimode large rectangular-core optical fibers. Self-guided nonlinear effects acting as spatial beam reshaping processes occurring in these newly-developed photonic structures lead to the generation of spectral broadenings in the visible and near-infrared spectral domains. Graphic Abstract
Introduction: Gut microbiota is associated with host characteristics such as age, sex, immune condition or frailty and is thought to be a key player in numerous human diseases. Nevertheless, its association with outcome in critically ill patients has been poorly investigated. The aim of this study is to assess the association between gut microbiota composition and Day-28 mortality in critically ill patients. Methods: Rectal swab at admission of every patient admitted to intensive care unit (ICU) between October and November 2019 was frozen at - 80 °C. DNA extraction was performed thanks to QIAamp® PowerFecal® Pro DNA kit (QIAgen®). V3-V4 regions of 16SRNA and ITS2 coding genes were amplified by PCR. Sequencing (2x250 bp paired-end) was performed on MiSeq sequencer (Illumina®). DADA2 pipeline on R software was used for bioinformatics analyses. Risk factors for Day-28 mortality were investigated by logistic regression. Results: Fifty-seven patients were consecutively admitted to ICU of whom 13/57 (23%) deceased and 44/57 (77%) survived. Bacteriobiota α-diversity was lower among non-survivors than survivors (Shannon and Simpson index respectively, p < 0.001 and p = 0.001) as was mycobiota α-diversity (respectively p = 0.03 and p = 0.03). Both gut bacteriobiota and mycobiota Shannon index were independently associated with Day-28 mortality in multivariate analysis (respectively OR: 0.19, 97.5 CI [0.04-0.60], p < 0.01 and OR: 0.29, 97.5 CI [0.09-0.75], p = 0.02). Bacteriobiota β-diversity was significantly different between survivors and non-survivors (p = 0.05) but not mycobiota β-diversity (p = 0.57). Non-survivors had a higher abundance of Staphylococcus haemolyticus, Clostridiales sp., Campylobacter ureolyticus, Akkermansia sp., Malassezia sympodialis, Malassezia dermatis and Saccharomyces cerevisiae, whereas survivors had a higher abundance of Collinsella aerofaciens, Blautia sp., Streptococcus sp., Faecalibacterium prausnitzii and Bifidobacterium sp. Conclusion: The gut bacteriobiota and mycobiota α diversities are independently associated with Day-28 mortality in critically ill patients. The causal nature of this interference and, if so, the underlying mechanisms should be further investigated to assess if gut microbiota modulation could be a future therapeutic approach.
Background epi-cblC is a recently discovered inherited disorder of intracellular vitamin B12 metabolism associating hematological, neurological, and cardiometabolic outcomes. It is produced by an epimutation at the promoter common to CCDC163P and MMACHC, which results from an aberrant antisense transcription due to splicing mutations in the antisense PRDX1 gene neighboring MMACHC. We studied whether the aberrant transcription produced a second epimutation by encompassing the CpG island of the TESK2 gene neighboring CCDC163P. Methods We unraveled the methylome architecture of the CCDC163P–MMACHC CpG island (CpG:33) and the TESK2 CpG island (CpG:51) of 17 epi-cblC cases. We performed an integrative analysis of the DNA methylome profiling, transcriptome reconstruction of RNA-sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-Seq) of histone H3, and transcription expression of MMACHC and TESK2. Results The PRDX1 splice mutations and activation of numerous cryptic splice sites produced antisense readthrough transcripts encompassing the bidirectional MMACHC/CCDC163P promoter and the TESK2 promoter, resulting in the silencing of both the MMACHC and TESK2 genes through the deposition of SETD2-dependent H3K36me3 marks and the generation of epimutations in the CpG islands of the two promoters. Conclusions The antisense readthrough transcription of the mutated PRDX1 produces an epigenetic silencing of MMACHC and TESK2. We propose using the term 'epi-digenism' to define this epigenetic disorder that affects two genes. Epi-cblC is an entity that differs from cblC. Indeed, the PRDX1 and TESK2 altered expressions are observed in epi-cblC but not in cblC, suggesting further evaluating the potential consequences on cancer risk and spermatogenesis.
Background Development of appropriateness indicators of medical interventions has become a major quality-of-care issue, especially in the domain of interventional cardiology (IC). The objective of this study was to develop and evaluate the accuracy of an indicator of the appropriateness of interventional cardiology acts (invasive coronary angiographies (ICA) and percutaneous coronary interventions (PCI)) in patients with coronary stable disease and silent ischemia, automated from a French registry. Methods All ICA and PCI recorded in a Regional IC Registry (ACIRA) and operated for a stable coronary artery disease or silent ischemia from January 1st to December 31th 2013 in eight IC hospitals of Aquitaine, southwestern France, were included. The indicator was developed to reflect European guidelines. Classification of appropriateness by the indicator, measured on the registry database, was compared to the classification of a reference standard (expert judgment applied through complete record review) on a random sample of 300 interventions. Accuracy parameters were estimated. A second version of the indicator was defined, based on the analysis of false negative and positive results, and its accuracy estimated. Results The second indicator accuracy was: sensitivity 63.5% (95% confidence interval CI [51.7–75.3]), specificity 76.0% (95%CI [70.4–81.6]), PPV 43.0% (95% CI [33.0–53.0]) and NPV 88.0% (95% CI [83.4–92.6]). When stratified on the type of act, parameters were better for ICA alone than for PCI. Conclusions Accuracy of the indicator should raise with improvement of database quality. Despite its average accuracy, it is already used as a benchmark indicator for cardiologists. It is sent annually to each IC center with value of the indicator at the region level to allow a comparison.
Background: Hyperoxia is associated with increased morbidity and mortality in the intensive care unit. Classical noninvasive measurements of oxygen saturation with pulse oximeters are unable to detect hyperoxia. The Oxygen Reserve Index (ORI) is a continuous noninvasive parameter provided by a multi-wave pulse oximeter that can detect hyperoxia. Primary objective was to evaluate the diagnostic accuracy of the ORI for detecting arterial oxygen tension (PaO2) > 100 mmHg in neurocritical care patients. Secondary objectives were to test the ability of ORI to detect PaO2 > 120 mmHg and the ability of pulse oximetry (SpO2) to detect PaO2 > 100 mmHg and PaO2 > 120 mmHg. Methods: In this single-center study, we collected ORI and arterial blood samples every 6 h for 3 consecutive days. Diagnostic performance was estimated using the area under the receiver operating characteristic curve (AUROC). Results: There were 696 simultaneous measurements of ORI and PaO2 in 62 patients. Considering the repeated measurements, the correlation between ORI and PaO2 was r = 0.13. The area under the receiver operating characteristic curve (AUROC), obtained to test the ability of ORI to detect PaO2 > 100 mmHg, was 0.567 (95% confidence interval = 0.566-0.569) with a sensitivity of 0.233 (95%CI = 0.230-0.235) and a specificity of 0.909 (95%CI = 0.907-0.910). The AUROC value obtained to test the ability of SpO2 to detect a PaO2 > 100 mmHg was 0.771 (95%CI = 0.770-0.773) with a sensitivity of 0.715 (95%CI = 0.712-0.718) and a specificity of 0.700 (95%CI = 0.697-0.703). The diagnostic performance of ORI and SpO2 for detecting PaO2 > 120 mmHg was AUROC = 0.584 (95%CI = 0.582-0.586) and 0.764 (95%CI = 0.762-0.766), respectively. The AUROC obtained for SpO2 was significantly higher than that for ORI (p < 0.01). Diagnostic performance was not affected by sedation, norepinephrine infusion, arterial partial pressure of carbon dioxide, hemoglobin level and perfusion index. Conclusion: In a specific population of brain-injured patients hospitalized in a neurointensive care unit, our results suggest that the ability of ORI to diagnose hyperoxia is relatively low and that SpO2 provides better detection.
Tomato ( Solanum lycopersicum ) is an established model for studying plant cuticle because of its thick cuticle covering and embedding the epidermal cells of the fruit. In this study, we screened an EMS mutant collection of the miniature tomato cultivar Micro-Tom for fruit cracking mutants and found a mutant displaying a glossy fruit phenotype. By using an established mapping-by-sequencing strategy, we identified the causal mutation in the SlSHN2 transcription factor that is specifically expressed in outer epidermis of growing fruit. The point mutation in the shn2 mutant introduces a K to N amino acid change in the highly conserved ‘mm’ domain of SHN proteins. The cuticle from shn2 fruit showed a ~ fivefold reduction in cutin while abundance and composition of waxes were barely affected. In addition to alterations in cuticle thickness and properties, epidermal patterning and polysaccharide composition of the cuticle were changed. RNAseq analysis further highlighted the altered expression of hundreds of genes in the fruit exocarp of shn2 , including genes associated with cuticle and cell wall formation, hormone signaling and response, and transcriptional regulation. In conclusion, we showed that a point mutation in the transcriptional regulator SlSHN2 causes major changes in fruit cuticle formation and its coordination with epidermal patterning.
Background There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID). Objectives The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes. Methods 950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR). Results 285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+) prevalent ); 206 (28.3%) during follow-up (COVID(+) incident )]. 2.6% COVID(+) athletes had abnormal ECGs, while 0.4% had an abnormal echocardiogram. During stress testing (following 7-day rest), COVID(+) athletes had a functional capacity of 12.8 ± 2.7 METS with only stress-induced premature ventricular ectopy in 10 (4.3%). Prevalence of CMR scar was comparable between COVID(+) athletes and controls [COVID(+) vs. COVID(−); 1/102 (1.0%) vs 1/28 (3.6%)]. During 289 ± 56 days follow-up, one athlete had ventricular tachycardia, with no obvious link with a SARS-CoV-2 infection. The proportion with troponin I and CRP values above the upper-limit threshold was comparable between pre- and post-infection (5.9% vs 5.9%, and 5.6% vs 8.7%, respectively). The proportion with D-Dimer values above the upper-limit threshold increased when comparing pre- and post-infection (7.9% vs 17.3%, P = 0.01). Conclusion The absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503).
In the so-called 1-2-3 Conjecture, the question is, for any connected graph not isomorphic to K2, whether we can label its edges with 1,2,3 so that no two adjacent vertices are incident to the same sum of labels. Many aspects of this conjecture have been investigated over the last past years, related both to the conjecture itself and to variations of it. Such variations include different generalisations, such as generalisations to more general graph structures (digraphs, hypergraphs, etc.) and generalisations with stronger distinction requirements. In this work, we introduce a new general problem, which holds essentially as a generalisation of the 1-2-3 Conjecture to a larger range. In this variant, a radius r≥2 is fixed, and the main task, given a graph, is, if possible, to label its edges so that any two vertices at distance at most r are distinguished through their sums of labels assigned to their edges at distance at most r. We investigate several general aspects of this problem, in particular the importance of r and its influence on the smallest number of labels needed to label graphs. We also show connections between our general problem and several other notions of graph theory, from both the distinguishing labelling field (e.g. irregularity strength of graphs) and the more general chromatic theory field (e.g. chromatic index of graphs).
Purpose Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. Materials & methods Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119–159 ² were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2–3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). Results 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76–0.84) to 0.85 (0.81–0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). Conclusions The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.
The term “middle class” is increasingly used to qualify the mass of people in developing countries who are neither poor nor rich and share consumption patterns historically associated with the western middle class. However, what differentiates them from the ideal-typical middle class, as well as the extent to which emerging middle classes differ across developing countries, has only been marginally documented by economists to date. This article proposes to scratch beneath the surface of the so-called middle-class that is burgeoning in developing countries by documenting the commonalities and differences hidden by the all-encompassing term of “middle class” for a set of developing countries exhibiting different levels of income, economic structures and socio-political systems: Brazil, Côte d’Ivoire, Turkey and Vietnam. Relying on quantitative and qualitative micro-economic data, our paper compares the objective characteristics (occupation, education, income), behavior and subjective expectations of the people standing in the middle of the income distribution in the four countries. Four main research questions structure the paper. Where is the middle? How is the middle specific? Who is in the middle? What does the middle aspire to? Results show that the middle-income group in each country covers distinct realities. Although some similar characteristics and behaviors are observable, our results reveal a strong heterogeneity within each national middle class, with no fewer than four to seven socio-economic subgroups, and strong country-specific traits as most of the subgroups are deeply rooted in the country’s specific historical trajectory. In each country, our analysis also unveils a pattern of bipolarization between a rather affluent and stable middle class and a “new” or more vulnerable one. Finally, middle class members appear to be characterized by an individualist positioning and the absence of a marked political commitment, challenging the common assumption that developing countries’ middle classes are agents of political change.
Objectives To identify the factors related to the presence of occult metastases before salvage total laryngectomy (STL) in rcN0 patients and to propose an algorithm to identify patients who do not require neck dissection (ND). Patients and methods This multicentric retrospective study included five centers with recruitment from 2008 to 2018. Inclusion criteria were: i) having been treated for laryngeal squamous cell carcinoma in first intention by radiotherapy (either alone or potentiated or preceded by induction chemotherapy), ii) having received STL with or without ND, iii) having an rcN0 neck at the time of STL. Results 120 patients met the inclusion criteria. The overall rate of occult metastases was 9.1 %. The rate was significantly higher in patients with an initial positive cN+ lymph node status (p < 0.005) and in advanced stages with rcT3-T4 lesions at recurrence (p < 0.005). Patients with occult metastases recurred earlier than those without (p = 0.002). The overall survival of patients was the same with or without ND (p = 0.16). There were significantly more healing complications requiring revision surgery in the group with ND than in the group without (p = 0.048). Conclusion ND does not confer a net survival benefit and is associated with significant complications. Patients without initial lymph node metastases who are rcT1-T2 at recurrence or rcT3-T4 with a recurrence period of more than 12 months could benefit from STL without ND. This decisional algorithm, which needs to be validated, would help avoid 58 % of ND procedures and their proven morbidity. Discipline Head and neck surgery.
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