Susceptibility of influenza B viruses to neuraminidase inhibitors: findings from the first 4 years (2008–2012) of the global Influenza Resistance Information Study (IRIS)

Poster Session: Antiviral Drugs and ResistanceBackground: Type B influenza virus infections continue to account for a substantial proportion of clinical illness. Little is known about comparative disease profiles by virus lineage. A global observational trial (the Influenza Resistance Information Study or IRIS; NCT00884117) was initiated to study neuraminidase inhibitor (NAI) susceptibility and the clinical and virological course of influenza in treated and untreated patients. Materials and Methods: Patients in the northern and southern hemispheres (USA, France, Germany, Poland, Norway, Hong Kong, Australia) with influenza-like illness and/or a positive rapid influenza test result were enrolled. Throat/nasal swabs were performed on Days 1, 3 (self-swab), 6 and 10 and tested for influenza A and B viruses by RT-PCR. Influenzapositive samples collected on Days 1, 6 or 10 were cultured and subsequently sequenced (HA and NA) and phenotypically tested for NAI susceptibility. The lineage of B viruses was determined from sequencing. Clinical information, including the scoring of seven influenza symptoms (scale: 0 [absent], 1 [mild], 2 [moderate], 3 [severe]), was recorded on diary cards by the patient or the patient’s legal guardian (Days 1–12). Symptoms were also assessed by the investigator at each visit. The decision to prescribe an NAI was left to the physician’s discretion. Results: In the first 4 years of IRIS (December 2008 to March 2012), 2262 influenza-positive (RT-PCR) patients were enrolled, of whom 697 presented with a type B influenza virus infection (564 Victoria, 98 Yamagata, 35 undetermined lineage). Most type B patients (402; 58%) were children aged < 13 years. A total of 330 (47%) type B patients were treated with oseltamivir (as monotherapy) within 2 days of symptom onset; a further 26 started oseltamivir 2 days after symptom onset. Eleven patients received zanamivir, one received amantadine and another received rimantidine. A total of 328 (47%) did not receive any influenza antiviral. Symptoms were mild to moderate on Day 1 (mean total score: 12.8, treated; 12.9, untreated), and the mean temperature on Day 1 was 38.2°C. All viruses obtained at baseline or postbaseline were susceptible to NAIs: mean (SD) IC50 values for oseltamivir were 4.8 nM (2.5 nM) and 5.5 nM (2.3 nM) for the Victoria and Yamagata viruses, respectively; the corresponding values for zanamivir were 2.0 nM (1.4 nM) and 2.9 nM (1.6 nM), respectively. No known NAI resistance mutations were detected by NA or HA population sequencing. The proportion of RT-PCR–positive patients on Day 6 was 130/309 (42.1%) for patients treated with oseltamivir and 152/312 (48.7%) for untreated patients. In Kaplan–Meier analyses, no significant differences in median time to influenza RNA clearance were found between oseltamivir-treated and -untreated patients, either in adults or children. The time to symptom resolution (all symptom scores ≤ 1) was 5 days (95% CI, 4–5 days) in oseltamivir-treated children and 6 days (95% CI, 5–6 days) in untreated children (P = .026), but no significant difference in symptom resolution time was found in adults (Kaplan–Meier analysis). Conclusions: Analysis of type B influenza viruses obtained globally between 2008 and 2012 showed that all pre-treatment B/Victoria and B/Yamagata viruses were susceptible to oseltamivir and zanamivir. Moreover, no resistant viruses were detected during treatment. Given the non-randomised design of this study, no definitive conclusions can be drawn with regard to the clinical benefit of oseltamivir in patients infected with type B influenza viruses.published_or_final_versio

The discovery of a five-image lensed quasar at z = 3.34 using PanSTARRS1 and Gaia

We report the discovery, spectroscopic confirmation, and mass modelling of the gravitationally lensed quasar system PS J0630-1201. The lens was discovered by matching a photometric quasar catalogue compiled from Pan-STARRS and WISE photometry to the Gaia DR1 catalogue, exploiting the high spatial resolution of the latter (FWHM $\sim$0.1") to identify the three brightest components of the lens. Follow-up spectroscopic observations with the WHT confirm the multiple objects are quasars at redshift $z_{q}=3.34$. Further follow-up with Keck AO high-resolution imaging reveals that the system is composed of two lensing galaxies and the quasar is lensed into a $\sim$2.8" separation four-image cusp configuration with a fifth image clearly visible, and a 1.0" arc due to the lensed quasar host galaxy. The system is well-modelled with two singular isothermal ellipsoids, reproducing the position of the fifth image. We discuss future prospects for measuring time delays between the images and constraining any offset between mass and light using the faintly detected Einstein arcs associated with the quasar host galaxy

Symmetry implies independence

Given a quantum system consisting of many parts, we show that symmetry of the system's state, i.e., invariance under swappings of the subsystems, implies that almost all of its parts are virtually identical and independent of each other. This result generalises de Finetti's classical representation theorem for infinitely exchangeable sequences of random variables as well as its quantum-mechanical analogue. It has applications in various areas of physics as well as information theory and cryptography. For example, in experimental physics, one typically collects data by running a certain experiment many times, assuming that the individual runs are mutually independent. Our result can be used to justify this assumption.Comment: LaTeX, contains 4 figure

New trends for metal complexes with anticancer activity

Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in ‘metals in medicine

Big Data Analytics. Analyse der prädiktiven Fähigkeit von Twitter-Sentiments auf die Entwicklung des Börsenkurses von Technologieunternehmen

Die Datenmengen vervielfachen sich in der heutigen Zeit konstant, was zum Begriff Big Data geführt hat. Durch diese Datenmengen entsteht ein neues Potenzial, Fragen zu beantworten. Eine dieser Fragestellungen, welche mithilfe von Big Data untersucht werden kann, ist, inwiefern die Social-Media-Daten die Veränderung von Börsenkursen voraussagen können. Diese Studie untersucht die prädiktive Fähigkeit von Twitter-Nachrichten im Zusammenhang mit einem Technologieunternehmen und dessen Börsenkurs anhand von zwei Anwendungsfällen. Konkret wird anhand der Twitter-Nachrichten mithilfe einer Sentimentanalyse die Stimmung der Twitter-Nutzer mit den Veränderungen des Börsenkurses verglichen. Diese Analyse wird anhand der Technologieunternehmen Facebook und Amazon vorgenommen. In einem ersten Schritt wird untersucht, ob eine Beziehung zwischen den Twitter-Sentiments und dem Börsenkurs besteht. In einem zweiten Schritt, ob die Twitter-Sentiments eine Voraussagekraft für die Veränderung des Börsenkurses haben. Die Auswertung zeigt bei beiden Unternehmen eine positive Korrelation der Twitter-Sentiments und des Börsenkurses auf. Weiter konnte mithilfe der Granger-Analyse eine signifikante Voraussagekraft der Twitter-Sentiments für die Börsenkurse beider Unternehmen ermittelt werden. Die Twitter-Sentiments können die Börsenkurse 13 h voraussagen

Global Egr1-miRNAs Binding Analysis in PMA-Induced K562 Cells Using ChIP-Seq

Although much is known about microRNAs' regulation in gene expression and their contributions in cell fate, to date, globally lineage-(cell-) specific identification of the binding events between a transcription factor and its targeting microRNA genes is still waiting for elucidation. In this paper, we performed a ChIP-Seq experiment to find the targeting microRNA genes of a transcription factor, Egr1, in human erythroleukemia cell line K562. We found Egr1 binding sites near the promoters of 124 distinct microRNA genes, accounting for about 42% of the miRNAs which have high-confidence predicted promoters (294). We also found EGR1 bind to another 63 pre-miRNAs. We chose 12 of the 187 microRNAs with Egr1 binding sites to perform ChIP-PCR assays and the positive binding signal from ChIP-PCR confirmed the ChIP-Seq results. Our experiments provide the first global binding profile between Egr1 and its targeting microRNA genes in PMA-treated K562 cells, which may facilitate the understanding of pathways controlling microRNA biology in this specific cell line

A relocatable ocean model in support of environmental emergencies

During the Costa Concordia emergency case, regional, subregional, and relocatable ocean models have been used together with the oil spill model, MEDSLIK-II, to provide ocean currents forecasts, possible oil spill scenarios, and drifters trajectories simulations. The models results together with the evaluation of their performances are presented in this paper. In particular, we focused this work on the implementation of the Interactive Relocatable Nested Ocean Model (IRENOM), based on the Harvard Ocean Prediction System (HOPS), for the Costa Concordia emergency and on its validation using drifters released in the area of the accident. It is shown that thanks to the capability of improving easily and quickly its configuration, the IRENOM results are of greater accuracy than the results achieved using regional or subregional model products. The model topography, and to the initialization procedures, and the horizontal resolution are the key model settings to be configured. Furthermore, the IRENOM currents and the MEDSLIK-II simulated trajectories showed to be sensitive to the spatial resolution of the meteorological fields used, providing higher prediction skills with higher resolution wind forcing.MEDESS4MS Project; TESSA Project; MyOcean2 Projectinfo:eu-repo/semantics/publishedVersio

Grassmannian flows and applications to nonlinear partial differential equations

We show how solutions to a large class of partial differential equations with nonlocal Riccati-type nonlinearities can be generated from the corresponding linearized equations, from arbitrary initial data. It is well known that evolutionary matrix Riccati equations can be generated by projecting linear evolutionary flows on a Stiefel manifold onto a coordinate chart of the underlying Grassmann manifold. Our method relies on extending this idea to the infinite dimensional case. The key is an integral equation analogous to the Marchenko equation in integrable systems, that represents the coodinate chart map. We show explicitly how to generate such solutions to scalar partial differential equations of arbitrary order with nonlocal quadratic nonlinearities using our approach. We provide numerical simulations that demonstrate the generation of solutions to Fisher--Kolmogorov--Petrovskii--Piskunov equations with nonlocal nonlinearities. We also indicate how the method might extend to more general classes of nonlinear partial differential systems.Comment: 26 pages, 2 figure

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types T and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting