Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

The Along-channel Salinity Distribution and its Response to River Discharge in Tidally-dominated Han River Estuary, South Korea

AbstractThe Han River Estuary (HRE), located on the west coast of South Korea, is well known for its macro tidal characteristics with a tidal range more than 8.5 m. This estuary has a distinctive salinity distribution because its system consists of 3 main channels and 3 rivers, through which major tidal flow and river discharge meet each other. To determine the effect of change in external forcing (e.g., river discharge and tidal variation) on the salinity, a numerical model is established and verified with observation. Based on previous observation, the main channel of HRE shows well- and/or partially-mixed estuary during spring and neap periods, respectively. The vertical stratification during the neap period is stronger than that during the spring due to decreasing turbulent mixing. The numerical results show that the salinity distribution during high river flow condition can be temporally and spatially characterized by river discharge. The asymmetries of the salinity distribution response to increasing and decreasing river discharge are indicated in this estuary. During high river flow conditions, the front of Incheon Harbor is within the region of the freshwater influence

Comb-rooted multi-channel synthesis of ultra-narrow optical frequencies of few Hz linewidth

We report a multi-channel optical frequency synthesizer developed to generate extremely stable continuous wave lasers directly out of the optical comb of an Er-doped fiber oscillator. Being stabilized to a high-finesse cavity with a fractional frequency stability of $3.8\times10^{-15}$ at 0.1 s, the comb-rooted synthesizer produces multiple optical frequencies of ultra-narrow linewidth of 1.0 Hz at 1 s concurrently with an output power of tens of mW per each channel. Diode-based stimulated emission by injection locking is a key mechanism that allows comb frequency modes to sprout up with sufficient power amplification but no loss of original comb frequency stability. Channel frequencies are individually selectable with a 0.1 GHz increment over the entire comb bandwidth spanning 4.25 THz around a 1550 nm center wavelength. A series of out-of-loop test results is discussed to demonstrate that the synthesizer is able to provide stable optical frequencies with the potential for advancing diverse ultra-precision applications such as optical clocks comparison, atomic line spectroscopy, photonic microwaves generation, and coherent optical telecommunications.Comment: 19 pages, 4 figure

Reactivation of hepatitis B (reverse seroconversion) after melphalan/dexamethasone therapy for primary amyloidosis: a case report

INTRODUCTION: Hepatitis B virus (HBV) reactivation (so-called reverse seroconversion) is a rare but known complication of hematopoietic stem cell transplantation, immunosuppressive therapy, or high-dose chemotherapy plus rituximab. This event is linked to a treatment-related fall in titers of antibodies to hepatitis B surface antigen (HBsAb) below the protective threshold level. CASE PRESENTATION: A 77-year-old Korean man diagnosed with primary amyloidosis was started on melphalan/dexamethasone combination therapy. During treatment, laboratory indices of hepatic function suddenly deteriorated, and he developed acute hepatitis through reverse HBV seroconversion, becoming positive for hepatitis B surface antigen (HBsAg) and negative for HBsAb. HBV DNA was also detectable in serum to a profound extent. Normal liver function was gradually restored during the course of antiviral therapy (entecavir). CONCLUSIONS: HBV reactivation may lead to fatal liver disease in a significant percentage of patients. As a result, physicians often screen for HBsAg and HBsAb prior to initiating chemotherapy, advising antiviral treatment in patients seropositive for HBsAg, even in the absence of hepatitis B e antigen. Here, a case of HBV reactivation is described, involving a patient given relatively low-dose chemotherapy (melphalan/dexamethasone) for primary amyloidosis

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Rivaroxabán; Aspirina; Infart cerebralRivaroxabán; Aspirina; Infarto cerebralRivaroxabán; Aspirin; Brain infarctBackground: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52-1.7). Conclusions: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide.Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.The NAVIGATE ESUS trial and the MRI Substudy were sponsored by Bayer AG

Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the Acute Brain Bleeding Analysis study

BACKGROUND AND PURPOSE: The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear. We examined the risk of HS associated with the use of NANSAIDs in Koreans. METHODS: We performed a nationwide, multicenter case-control study from 2002 to 2004. This study included 940 nontraumatic acute HS cases in patients aged 30 to 84 years, with an absence of a history of stroke or hemorrhage-prone brain lesions, alongside 940 community controls, matched to each case by age and sex. Pretrained interviewers obtained information on prescription drugs as well as over-the-counter drugs taken within 14 days before the onset of stroke. We adjusted potential confounders, including family histories of stroke, histories of hypertension, smoking, alcohol consumption, high salt intake, and laborious work hours. The adjusted ORs and their 95% CIs were calculated by conditional logistic regression. RESULTS: The proportion of NANSAIDs exposure within 14 days was 2.9% for HS patients and 2.0% for the controls. The adjusted odds ratios of stroke in NANSAIDs users compared with nonusers was 1.12 (95% CI, 0.77 to 1.65) for all HS, 1.03 (95% CI, 0.49 to 2.18) for subarachnoid hemorrhage, and 1.19 (95% CI, 0.76 to 1.87) for intracerebral hemorrhage. CONCLUSIONS: No increased risk of HS either subarachnoid hemorrhage or intracerebral hemorrhage was found among NANSAIDs users.This study was partially supported by the Korean Food and Drug Administration

Aerodynamic Shape Optimization using Overset Mesh Technique for Multiple Body Aircraft Geometries

A new design approach for a delicate treatment of complex geometries such as wing/body configuration is arranged using overset mesh technique under large scale computing environment. For the in-depth study of the flow physics and highly accurate design, several special overlapped structured blocks such as collar grid, tip-cap grid, and etc. which are commonly used in refined drag prediction are adopted to consider the applicability of the design code to practical problems. Various pre- and post-processing techniques for overset flow analysis and sensitivity analysis are devised or implemented to adapt overset mesh technique to the design optimization problem based on Gradient Based Optimization Method (GBOM). In the pre-processing, the convergence characteristics of the flow solver and sensitivity analysis are improved by overlap optimization method. Moreover, a new post-processing method, Spline-Boundary Intersecting Grid (S-BIG) scheme, is proposed by considering the ratio of cell area for more refined prediction of aerodynamic coefficients and convenient evaluation of sensitivities under parallel computing environment. For the sensitivity analysis, adjoint formulations for overset boundary conditions are implemented into the fully hand-differentiated sensitivity analysis code. A smooth geometric modification on the overlapped surface boundaries and evaluation of grid sensitivities can be performed by mapping from planform coordinate to the surface meshes with Hicks-Henne function. Careful design works for the drag minimization problem of a transonic wing and a wing/body configuration are performed using the newly-developed and -applied overset mesh techniques. And the design results from conventional design problem demonstrate the capability of the present design approach successfully.The authors appreciate financial support by the Brain Korea-21 Project for the Mechanical and Aerospace Engineering Research at Seoul National University and by the Korea Science and Engineering Foundation (Grant R01-2005-000-10059-0)

Sismicità all’Etna dal 1989 al 2010: evidenze sull’evoluzione spazio-temporale dell’attività sismica

Il Monte Etna, uno dei più attivi vulcani basaltici tra i più monitorati al mondo, è sede di una notevole attività sismica e vulcanica. Esso è ubicato in Sicilia orientale in un complesso quadro geodinamico, dove le principali strutture tettoniche regionali giocano un ruolo chiave nei processi dinamici del vulcano. La sismicità dell’Etna si manifesta con un elevato rate di terremoti di bassa e moderata energia che, a volte, a causa dell’estrema superficialità della sorgente, provocano danni ai centri abitati prossimi all’area epicentrale. Il monitoraggio sistematico dell’attività sismica etnea è effettuato sin dal 1989, mediante una rete sismica locale permanente che nel tempo è stata oggetto di importanti miglioramenti. La prima configurazione di rete era costituita da circa 10 stazioni analogiche con sensori a corto periodo gestita dall’Istituto Internazionale di Vulcanologia (IIV-CNR). Nel 1994, una rete sismica costituita da circa 40 stazioni (analogiche con sensori a corto periodo) fu installata sull’Etna nell’ambito del Progetto Poseidon. Nel 2001, le reti gestite dall’IIV-CNR e dal Progetto Poseidon confluirono nell’Istituto Nazionale di Geofisica e Vulcanologia (INGV); attualmente la rete sismica, costituita da circa 50 stazioni digitali equipaggiate con sismometri broadband a tre componenti, è gestita dalla Sezione di Catania dell’INGV. Nel periodo 1989-1999, il catalogo dei terremoti risulta costituito da circa 2000 eventi con soglia di completezza per magnitudo pari a 2.0; dal 1999 ad oggi contiene circa 6000 terremoti con soglia di completezza per magnitudo 1.5. La capacità di detezione della rete è migliorata nel tempo permettendo di registrare e localizzare anche gli eventi meno energetici (M≥1.0). In questo lavoro, vengono presentati i caratteri predominanti della sismicità etnea negli ultimi 20 anni, con un maggiore dettaglio della distribuzione spazio-temporale della sismicità verificatasi dal 1999. L’analisi della attività sismica rappresenta un utile strumento per l’interpretazione delle dinamiche che hanno contraddistinto numerose ed importanti eruzioni (2001, 2002-03, 2004, 2006, 2008-09). In particolare, la variazione del rilascio energetico della sismicità ha contribuito in maniera significativa ad identificare i probabili processi geodinamici legati alla ricarica del sistema magmatico del vulcano. La distribuzione spaziale della sismicità ha consentito di evidenziare inoltre l’esistenza di diverse aree sismogenetiche caratterizzate da un differente rate sismico, profondità focali e cinematica delle strutture associate. Infine, osservando le caratteristiche della sismicità nel lungo periodo, differenti settori del vulcano sono risultati maggiormente attivi in relazione ai più importanti recenti eventi eruttivi

Apoptosis Is Induced by Hantaviruses in Cultured Cells

AbstractHantaviruses replicate in primary and cultured animal cells with little or no cytopathic effect. We report here that the cultured Vero E6 cells infected by the Hantaan or by the Prospect Hill viruses exhibited characteristic features of apoptosis, including condensation and segmentation of nuclei and internucleosomal cleavage of nuclear DNA. Apoptosis was not seen in the cells adsorbed by UV-inactivated virus, indicating that the viral replication is required for the induction of apoptosis. Furthermore, level of the proto-oncogenic Bcl-2 protein was significantly reduced, whereas its mRNA level remained unchanged in Hantaan virus-infected cells, suggesting possible involvement and posttranscriptional regulation of this antiapoptotic protein in the process