Evaluation of the Coverage of 3 Antibiotic Regimens for Neonatal Sepsis in the Hospital Setting Across Asian Countries.

Importance: High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens. Objective: To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries. Design, Setting, and Participants: A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019. Exposures: The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted. Main Outcomes and Measures: Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level. Results: Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from -15.9% in China to -52.9% in Indonesia. Conclusions and Relevance: This study's findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption

Multi-Scale Simulation Modeling for Prevention and Public Health Management of Diabetes in Pregnancy and Sequelae

Diabetes in pregnancy (DIP) is an increasing public health priority in the Australian Capital Territory, particularly due to its impact on risk for developing Type 2 diabetes. While earlier diagnostic screening results in greater capacity for early detection and treatment, such benefits must be balanced with the greater demands this imposes on public health services. To address such planning challenges, a multi-scale hybrid simulation model of DIP was built to explore the interaction of risk factors and capture the dynamics underlying the development of DIP. The impact of interventions on health outcomes at the physiological, health service and population level is measured. Of particular central significance in the model is a compartmental model representing the underlying physiological regulation of glycemic status based on beta-cell dynamics and insulin resistance. The model also simulated the dynamics of continuous BMI evolution, glycemic status change during pregnancy and diabetes classification driven by the individual-level physiological model. We further modeled public health service pathways providing diagnosis and care for DIP to explore the optimization of resource use during service delivery. The model was extensively calibrated against empirical data.Comment: 10 pages, SBP-BRiMS 201

Assessment of retinal vascular calibres as a biomarker of disease activity in birdshot chorioretinopathy

Purpose Birdshot chorioretinopathy (BCR) is a potentially blinding ocular disorder involving the retinal vasculature and choroid without any systemic manifestations. The objective of the study was to describe vascular calibre changes in BCR and analyse the possibility of this optical biomarker for staging and monitoring disease activity in BCR. Methods This retrospective case–control study at a tertiary referral eye centre in the UK included 33 eyes from 21 patients with BCR and equal number of eyes from control subjects. Diagnosis of BCR was confirmed on fundus fluorescein and indocyanine green angiography. Vascular calibres were measured using validated semiautomated software. Results Patients with BCR had smaller retinal venular calibres central retinal venular equivalent (CRVE) than controls (211.3 versus 227.9 μm, p = 0.008). After adjusting for variables, the difference between the two groups for CRVE at baseline was statistically significant based on two different analysis methods. Central retinal venular equivalent (CRVE) was lower at the 6-month follow-up visit (206.2 versus 213.8 μm, p-value = 0.03), and arteriole-to-venule ratio was larger (0.74 versus 0.71, p = 0.04) in subjects with BCR. Arteriolar calibre (CRAE) remained the same. Conclusion This study provides novel insight into the pattern of vascular involvement in BCR. There was significant difference in the CRVE in patients with BCR. More studies are needed to correlate this data with visual function and treatment outcome and to validate the findings

Four-country surveillance of intestinal intussusception and diarrhoea in children

Aim: Establishment of baseline epidemiology of intussusception in developing countries has become a necessity with the possibility of reintroduction of rotavirus vaccine. The current study assessed the seasonal trend in cases admitted with intussusceptions and dehydrating acute watery diarrhoea in children aged 2 months to 10 years. Methods: In a prospective surveillance study, teaching and research hospital sites in India (Lucknow and Nagpur), Brazil (Fortazela), Egypt (Ismailia) and Kenya (Nairobi) established a surveillance where a network of hospitals with surgical facilities catered to a reference population of about 1-2 million for reporting of intussusception. One large hospital per site also recruited admitted cases of acute watery diarrhoea. Results: From April 2004 to March 2006, 173 and 2346 cases of intussusception and diarrhoea, respectively, were recruited. Cases of intussusception had no apparent seasonality. Most cases of intussusception (61.3%) (107/173) were in the ≤1 year age group, with males comprising 68.8% (119/173) of all cases. Hospital mortality of intussusception was 4.2% (4/96). Cases of diarrhoea peaked in March, with 56.6% (1328/2346) of admitted cases being males. Majority (83.1%) of cases of diarrhoea had received antibiotics, and the hospital mortality was 0.8% (18/2280). Conclusion: Intussusception in the four participating countries exhibited no seasonal trend. We found that it is feasible to establish a surveillance network for intussusception in developing countries. Future efforts must define population base before the introduction of rotavirus vaccine and continue for some years thereafter. © 2009 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

Cosmology of the selfaccelerating third order Galileon

In this paper we start from the original formulation of the galileon model with the original choice for couplings to gravity. Within this framework we find that there is still a subset of possible Lagrangians that give selfaccelerating solutions with stable spherically symmetric solutions. This is a certain constrained subset of the third order galileon which has not been explored before. We develop and explore the background cosmological evolution of this model drawing intuition from other even more restricted galileon models. The numerical results confirm the presence of selfacceleration, but also reveals a possible instability with respect to galileon perturbations.Comment: 30 pages, 24 figure

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes

Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05). Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points

Exact Diagonalization of Two Quantum Models for the Damped Harmonic Oscillator

The damped harmonic oscillator is a workhorse for the study of dissipation in quantum mechanics. However, despite its simplicity, this system has given rise to some approximations whose validity and relation to more refined descriptions deserve a thorough investigation. In this work, we apply a method that allows us to diagonalize exactly the dissipative Hamiltonians that are frequently adopted in the literature. Using this method we derive the conditions of validity of the rotating-wave approximation (RWA) and show how this approximate description relates to more general ones. We also show that the existence of dissipative coherent states is intimately related to the RWA. Finally, through the evaluation of the dynamics of the damped oscillator, we notice an important property of the dissipative model that has not been properly accounted for in previous works; namely, the necessity of new constraints to the application of the factorizable initial conditions.Comment: 19 pages, 2 figures, ReVTe

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Intelligent Health Monitoring of Machine Bearings Based on Feature Extraction

This document is the Accepted Manuscript of the following article: Mohammed Chalouli, Nasr-eddine Berrached, and Mouloud Denai, ‘Intelligent Health Monitoring of Machine Bearings Based on Feature Extraction’, Journal of Failure Analysis and Prevention, Vol. 17 (5): 1053-1066, October 2017. Under embargo. Embargo end date: 31 August 2018. The final publication is available at Springer via DOI: https://doi.org/10.1007/s11668-017-0343-y.Finding reliable condition monitoring solutions for large-scale complex systems is currently a major challenge in industrial research. Since fault diagnosis is directly related to the features of a system, there have been many research studies aimed to develop methods for the selection of the relevant features. Moreover, there are no universal features for a particular application domain such as machine diagnosis. For example, in machine bearing fault diagnosis, these features are often selected by an expert or based on previous experience. Thus, for each bearing machine type, the relevant features must be selected. This paper attempts to solve the problem of relevant features identification by building an automatic fault diagnosis process based on relevant feature selection using a data-driven approach. The proposed approach starts with the extraction of the time-domain features from the input signals. Then, a feature reduction algorithm based on cross-correlation filter is applied to reduce the time and cost of the processing. Unsupervised learning mechanism using K-means++ selects the relevant fault features based on the squared Euclidian distance between different health states. Finally, the selected features are used as inputs to a self-organizing map producing our health indicator. The proposed method is tested on roller bearing benchmark datasets.Peer reviewe