Transcriptional and clonal characterization of B cell plasmablast diversity following primary and secondary natural DENV infection

Antibody-mediated humoral immunity is thought to play a central role in mediating the immunopathogenesis of acute DENV infection, but limited data are available on the diversity, specificity, and functionality of the antibody response at the molecular level elicited by primary or secondary DENV infection. In order to close this functional gap in our understanding of DENV-specific humoral immunity, we utilized high-throughput single cell RNA sequencing to investigate B cells circulating in both primary and secondary natural DENV infections. We captured full-length paired immunoglobulin receptor sequence data from 9,027 B cells from a total of 6 subjects, including 2,717 plasmablasts. In addition to IgG and IgM class-switched cells, we unexpectedly found a high proportion of the DENV-elicited plasmablasts expressing IgA, principally in individuals with primary DENV infections. These IgA class-switched cells were extensively hypermutated even in individuals with a serologically confirmed primary DENV infection. Utilizing a combination of conventional biochemical assays and high-throughput shotgun mutagenesis, we determined that DENV-reactive IgA classswitched antibodies represent a significant fraction of DENV-reactive Igs generated in response to DENV infection, and that they exhibit a comparable epitope specificity to DENV-reactive IgG antibodies. These results provide insight into the molecular-level diversity of DENV-elicited humoral immunity and identify a heretofore unappreciated IgA plasmablast response to DENV infection

Respiratory and allergic health effects in a young population in proximity of a major industrial park in Oman

Background: The Sohar Industrial Zone (SIZ), Oman, which started operating in 2006, contains many industries that potentially affect health of the local population. The aim of this study was to evaluate the health effects in a young population living near SIZ. Methods: Retrospective health care visits for acute respiratory diseases (ARD), asthma, conjunctivitis and dermatitis for children of ages 5-10, ≥20 km to represent high, intermediate and control exposure zones respectively. Age and gender-specific monthly counts of visits of the selected diseases were modeled using generalized additive models controlling for time trends. The high and intermediate exposure zones were later combined together due to similarity of associations. Exposure effect modification by age, gender and socioeconomic status (SES) was also tested. Results: Living within 10 km from SIZ showed greater association with ARD (RR: 2.5; 95% CI: 2.3-2.7)), asthma (RR: 3.7; 95% CI: 3.1-4.5), conjunctivitis (RR: 3.1; 95% CI: 2.9-3.5), and dermatitis (RR: 2.7; 95% CI: 2.5-3.0) when compared to the control zone. No differences in associations were found for gender and SES groups; greater effects were noticed in the ≤14 years old group for asthma. Conclusion: This is the first study conducted in Oman examining the health effects of a young population living in proximity of an industrial park. We hope that these findings will contribute in future developments of environmental and public health policies in Oman

Clinical predictors of all‐cause mortality in patients presenting to specialist heart failure clinic with raised NT‐proBNP and no heart failure

Aims Clinical outcomes for patients suspected of having heart failure (HF) who do not meet the diagnostic criteria of any type of HF by echocardiography remain unknown. The aim of this study was to investigate the clinical predictors of all‐cause mortality in patients with suspected HF, a raised N‐terminal pro‐b‐type natriuretic peptide (NTproBNP) and who do not meet the diagnostic criteria of any type of HF by echocardiography. Methods and results Relevant data were taken from the S heffield HEA rt F ailure (SHEAF) registry (222349P4). The inclusion criteria were presence of symptoms raising suspicion of HF, NTproBNP > 400 pg/mL, and preserved left ventricular function. Exclusion criteria were any type of HF by echocardiography. The outcome was defined as all‐cause mortality. Cox proportional‐hazards regression model was used to investigate the association between the survival time of patients and clinical variables; 1031 patients were identified with NTproBNP > 400 pg/mL but who did not have echocardiographic evidence of HF. All‐cause mortality was 21.5% (222 deaths) over the mean follow‐up (FU) period of 6 ± 2 years. NTproBNP was similar in patients who were alive or dead (P = 0.96). However, age (HR 1, P 627 pg/mL, NYHA class predicted death (II, 19.6%; III, 27.4%; IV, 66.7%; P < 0.01). Conclusions Patients with no HF on echocardiography but raised NTproBNP suffer excess mortality particularly in the presence of certain clinical variables. Age, male gender, worsening CKD stage, presence of COPD, and dementia are independently associated with all‐cause mortality in these patients. An NTproBNP > 627 pg/mL coupled with NYHA class could identify patients at greatest risk of death

Enabling P4 Network Telemetry in Edge Micro Data Centers With Kubernetes Orchestration

Integrating computation resources with networking technologies is an hot research topic targeting the optimization of containers deployment on a set of host machines interconnected by a network infrastructure. Particularly, next generation edge nodes will offer significant advantages leveraging on integrated computation resources and networking awareness, enabling configurable, granular and monitorable quality of service to different micro-services, applications and tenants, especially in terms of bounded end-to-end latency. In this regard, SDN is a key technology enabling network telemetry and traffic switching with the granularity of the single traffic flow. However, currently available solutions are based on legacy SDN techniques, not enabling the matching of tunneled traffic, and thus require a tricky integration inside the hosts where containers are deployed. This work considers Kubernetes clusters deployed on next generation edge micro data center platforms and proposes an innovative SDN solution exploiting the P4 technology to gain visibility inside tunnelled traffic exchanged among pods. This way, the integration is achieved at the control plane level through the communication between Kubernetes and the SDN controller. The proposed solution is experimentally validated including a comprehensive framework enabling effective traffic switching and in-band telemetry at pod level. The major paper contributions consist in the design and the development of: (i) the networking applications at SDN control plane level; (ii) the P4 switch pipeline at the data plane level; (iii) the monitoring system used to collect, aggregate and elaborate the telemetry data

Development and validation of the Diabetes Numeracy Test (DNT)

<p>Abstract</p> <p>Background</p> <p>Low literacy and numeracy skills are common. Adequate numeracy skills are crucial in the management of diabetes. Diabetes patients use numeracy skills to interpret glucose meters, administer medications, follow dietary guidelines and other tasks. Existing literacy scales may not be adequate to assess numeracy skills. This paper describes the development and psychometric properties of the Diabetes Numeracy Test (DNT), the first scale to specifically measure numeracy skills used in diabetes.</p> <p>Methods</p> <p>The items of the DNT were developed by an expert panel and refined using cognitive response interviews with potential respondents. The final version of the DNT (43 items) and other relevant measures were administered to a convenience sample of 398 patients with diabetes. Internal reliability was determined by the Kuder-Richardson coefficient (KR-20). An <it>a priori </it>hypothetical model was developed to determine construct validity. A shortened 15-item version, the DNT15, was created through split sample analysis.</p> <p>Results</p> <p>The DNT had excellent internal reliability (KR-20 = 0.95). The DNT was significantly correlated (p < 0.05) with education, income, literacy and math skills, and diabetes knowledge, supporting excellent construct validity. The mean score on the DNT was 61% and took an average of 33 minutes to complete. The DNT15 also had good internal reliability (KR-20 = 0.90 and 0.89). In split sample analysis, correlations of the DNT-15 with the full DNT in both sub-samples was high (rho = 0.96 and 0.97, respectively).</p> <p>Conclusion</p> <p>The DNT is a reliable and valid measure of diabetes related numeracy skills. An equally adequate but more time-efficient version of the DNT, the DNT15, can be used for research and clinical purposes to evaluate diabetes related numeracy.</p

Long term (5 Year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

&lt;b&gt;Background:&lt;/b&gt; Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure. &lt;br&gt;&lt;/br&gt; &lt;br&gt;&lt;/br&gt; &lt;b&gt;Methods:&lt;/b&gt; Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT. &lt;br&gt;&lt;/br&gt; &lt;br&gt;&lt;/br&gt; &lt;b&gt;Results:&lt;/b&gt; 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years

Infrared Spectroscopy on Smoke Produced by Cauterization of Animal Tissue

In view of in vivo surgical smoke studies a difference-frequency-generation (DFG) laser spectrometer (spectral range 2900–3144 cm−1) and a Fourier-transform infrared (FTIR) spectrometer were employed for infrared absorption spectroscopy. The chemical composition of smoke produced in vitro with an electroknife by cauterization of different animal tissues in different atmospheres was investigated. Average concentrations derived are: water vapor (0.87%), methane (20 ppm), ethane (4.8 ppm), ethene (17 ppm), carbon monoxide (190 ppm), nitric oxide (25 ppm), nitrous oxide (40 ppm), ethyne (50 ppm) and hydrogen cyanide (25 ppm). No correlation between smoke composition and the atmosphere or the kind of cauterized tissue was found

Phase transitions in biological membranes

Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure