Red blood cells (RBCs) visualisation in bifurcations and bends

Bifurcating networks are commonly found in nature. One example is the microvascular system, composed of blood vessels consecutively branching into daughter vessels, driving the blood into the capillaries, where the red blood cells (RBCs) are responsible for delivering O 2 and up taking cell waste and CO 2 . In this preliminary study, we explore a microfluidic bifurcating geometry inspired by such biological models, for investigating RBC partitioning as well as RBC-plasma separation favored by the consecutive bifurcating channels. A biomimetic design rule [1] based on Murray’s law [2] was used to set the channels’ dimensions along the network, which consists of consecutive bifurcating channels of reducing diameter. The ability to apply differential flow resistances by controlling the flow rates at the end of the network allowed us to monitor the formation of a cell-free layer (CFL) for different flow conditions at haematocrits of 1% and 5%. We have also compared the values of CFL thickness determined directly by the measurement on the projection image created from a stack of images or indirectly by analyzing the intensity profile in the same projection. The results obtained from this study confirm the potential to study RBC partitioning along bifurcating networks, which could be of particular interest for the separation of RBCs from plasma in point-of-care devices.JF would like to thank Professor Graça Minas and her coworkers for providing the laboratory facilities and technical help during the experiments.info:eu-repo/semantics/publishedVersio

Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods

Kikuchi-Fujimoto disease

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild fever and night sweats. Less frequent symptoms include weight loss, nausea, vomiting, sore throat. Kikuchi-Fujimoto disease is an extremely rare disease known to have a worldwide distribution with higher prevalence among Japanese and other Asiatic individuals. The clinical, histopathological and immunohistochemical features appear to point to a viral etiology, a hypothesis that still has not been proven. KFD is generally diagnosed on the basis of an excisional biopsy of affected lymph nodes. Its recognition is crucial especially because this disease can be mistaken for systemic lupus erythematosus, malignant lymphoma or even, though rarely, for adenocarcinoma. Clinicians' and pathologists' awareness of this disorder may help prevent misdiagnsois and inappropriate treatment. The diagnosis of KFD merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young individuals presenting with posterior cervical lymphadenopathy. Treatment is symptomatic (analgesics-antipyretics, non-steroidal anti-inflammatory drugs and, rarely, corticosteroids). Spontaneous recovery occurs in 1 to 4 months. Patients with Kikuchi-Fujimoto disease should be followed-up for several years to survey the possibility of the development of systemic lupus erythematosus

Syndromic Recognition of Influenza A Infection in a Low Prevalence Community Setting

BACKGROUND: With epidemics of influenza A virus infection, people and medical professionals are all concerned about symptoms or syndromes that may indicate the infection with influenza A virus. METHODOLOGY/PRINCIPAL FINDINGS: A prospective study was performed at a community clinic of a metropolitan area. Throat swab was sampled for 3-6 consecutive adult patients with new episode (<3 days) of respiratory tract infection every weekday from Dec. 8, 2005 to Mar. 31, 2006. Demographic data, relevant history, symptoms and signs were recorded. Samples were processed with multiplex real time PCR for 9 common respiratory tract pathogens and by virus culture. Throat swab samples were positive for Influenza A virus with multiplex real time PCR system in 12 of 240 patients. The 12 influenza A positive cases were with more clusters and chills than the other 228. Certain symptoms and syndromes increased the likelihood of influenza A virus infection. The syndrome of high fever plus chills plus cough, better with clustering of cases in household or workplace, is with the highest likelihood (positive likelihood ratio 95; 95% CI 12-750). Absence of both cluster and chills provides moderate evidence against the infection (negative likelihood ratio 0.51; 95% CI 0.29-0.90). CONCLUSIONS/SIGNIFICANCE: Syndromic recognition is not diagnostic but is useful for discriminating between influenza A infection and common cold. In addition to relevant travel history, confirmatory molecular test can be applied to subjects with high likelihood when the disease prevalence is low

Comparison of alternative risk adjustment measures for predictive modeling: high risk patient case finding using Taiwan's National Health Insurance claims

<p>Abstract</p> <p>Background</p> <p>Predictive modeling presents an opportunity to contain the expansion of medical expenditures by focusing on very few people. Evaluation of how risk adjustment models perform in predictive modeling in Taiwan or Asia has been rare. The aims of this study were to evaluate the performance of different risk adjustment models (the ACG risk adjustment system and prior expenditures) in predictive modeling, using Taiwan's National Health Insurance (NHI) claims data, and to compare characteristics of potentially high-expenditure subjects identified through different models.</p> <p>Methods</p> <p>A random sample of NHI enrollees continuously enrolled in 2002 and 2003 (n = 164,562) was selected. Health status measures and total expenditures derived from 2002 NHI claims data were used to predict the possibility of becoming 2003 top users. Statistics-based indicators (C-statistics, sensitivity, & Predictive Positive Value) and characteristics of identified top groups by different models (expenditures and prevalence of manageable diseases) were presented.</p> <p>Results</p> <p>Both diagnosis-based and prior expenditures models performed much better than the demographic model. Diagnosis-based models were better in identifying top users with manageable diseases; prior expenditures models were better in statistics-based indicators and identifying people with higher average expenditures. Prior expenditures status could correctly identify more actual top users than diagnosis-based or demographic models. The proportions of actual top users that could be identified by diagnosis-based models alone were much lower than that identified by prior expenditures status.</p> <p>Conclusions</p> <p>Predicted top users identified by different models have different characteristics and there is little agreement between modes regarding which groups would be potentially top users; therefore, which model to use should depend on the purpose of predictive modeling. Prior expenditures are a more powerful tool than diagnosis-based risk adjusters in terms of correctly identifying more actual high expenditures users. There is still much room left for improvement of diagnosis-based models in predictive modeling.</p

Glycans as receptors for influenza pathogenesis

Influenza A viruses, members of the Orthomyxoviridae family, are responsible for annual seasonal influenza epidemics and occasional global pandemics. The binding of viral coat glycoprotein hemagglutinin (HA) to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of these viruses. Scientists believe that a switch in the binding specificity of HA from Neu5Acα2-3Gal linked (α2-3) to Neu5Acα2-6Gal linked (α2-6) glycans is essential for the crossover of the viruses from avian to human hosts. However, studies have shown that the classification of glycan binding preference of HA based on sialic acid linkage alone is insufficient to establish a correlation between receptor specificity of HA and the efficient transmission of influenza A viruses. A recent study reported extensive diversity in the structure and composition of α2-6 glycans (which goes beyond the sialic acid linkage) in human upper respiratory epithelia and identified different glycan structural topologies. Biochemical examination of the multivalent HA binding to these diverse sialylated glycan structures also demonstrated that high affinity binding of HA to α2-6 glycans with a characteristic umbrella-like structural topology is critical for efficient human adaptation and human-human transmission of influenza A viruses. This review summarizes studies which suggest a new paradigm for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis.National Institute of General Medical Sciences (U.S.) (Glue Grant U54 GM62116)National Institutes of Health (U.S.) (Grant GM57073)Singapore-MIT Alliance for Research and Technolog

Detection of Resistance Mutations to Antivirals Oseltamivir and Zanamivir in Avian Influenza A Viruses Isolated from Wild Birds

The neuraminidase (NA) inhibitors oseltamivir and zanamivir are the first-line of defense against potentially fatal variants of influenza A pandemic strains. However, if resistant virus strains start to arise easily or at a high frequency, a new anti-influenza strategy will be necessary. This study aimed to investigate if and to what extent NA inhibitor–resistant mutants exist in the wild population of influenza A viruses that inhabit wild birds. NA sequences of all NA subtypes available from 5490 avian, 379 swine and 122 environmental isolates were extracted from NCBI databases. In addition, a dataset containing 230 virus isolates from mallard collected at Ottenby Bird Observatory (Öland, Sweden) was analyzed. Isolated NA RNA fragments from Ottenby were transformed to cDNA by RT-PCR, which was followed by sequencing. The analysis of genotypic profiles for NAs from both data sets in regard to antiviral resistance mutations was performed using bioinformatics tools. All 6221 sequences were scanned for oseltamivir- (I117V, E119V, D198N, I222V, H274Y, R292K, N294S and I314V) and zanamivir-related mutations (V116A, R118K, E119G/A/D, Q136K, D151E, R152K, R224K, E276D, R292K and R371K). Of the sequences from the avian NCBI dataset, 132 (2.4%) carried at least one, or in two cases even two and three, NA inhibitor resistance mutations. Swine and environmental isolates from the same data set had 18 (4.75%) and one (0.82%) mutant, respectively, with at least one mutation. The Ottenby sequences carried at least one mutation in 15 cases (6.52%). Therefore, resistant strains were more frequently found in Ottenby samples than in NCBI data sets. However, it is still uncertain if these mutations are the result of natural variations in the viruses or if they are induced by the selective pressure of xenobiotics (e.g., oseltamivir, zanamivir)

Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example

<p>Abstract</p> <p>Background</p> <p>Positive controls are an integral component of any sensitive molecular diagnostic tool, but this can be affected, if several mutations are being screened in a scenario of a pandemic or newly emerging disease where it can be difficult to acquire all the necessary positive controls from the host. This work describes the development of a synthetic oligo-cassette for positive controls for accurate and highly sensitive diagnosis of several mutations relevant to influenza virus drug resistance.</p> <p>Results</p> <p>Using influenza antiviral drug resistance mutations as an example by employing the utility of synthetic paired long oligonucleotides containing complementary sequences at their 3' ends and utilizing the formation of oligonucleotide dimers and DNA polymerization, we generated ~170bp dsDNA containing several known specific neuraminidase inhibitor (NAI) resistance mutations. These templates were further cloned and successfully applied as positive controls in downstream assays.</p> <p>Conclusion</p> <p>This approach significantly improved the development of diagnosis of resistance mutations in terms of time, accuracy, efficiency and sensitivity, which are paramount to monitoring the emergence and spread of antiviral drug resistant influenza strains. Thus, this may have a significantly broader application in molecular diagnostics along with its application in rapid molecular testing of all relevant mutations in an event of pandemic.</p

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV