Performance evaluation of a rapid molecular diagnostic, MultiCode based, sample-to-answer assay for the simultaneous detection of Influenza A, B and respiratory syncytial viruses

AbstractBackgroundClinical signs and symptoms of different airway pathogens are generally indistinguishable, making laboratory tests essential for clinical decisions regarding isolation and antiviral therapy. Immunochromatographic tests (ICT) and direct immunofluorescence assays (DFA) have lower sensitivities and specificities than molecular assays, but have the advantage of quick turnaround times and ease-of-use.ObjectiveTo evaluate the performance of a rapid molecular assay, ARIES FluA/B & RSV, using laboratory developed RT-PCR assays (LDA), ICT (BinaxNOW) and DFA.MethodsAnalytical and clinical performance were evaluated in a retrospective study arm (stored respiratory samples obtained between 2006–2015) and a prospective study arm (unselected fresh clinical samples obtained between December 2015 and March 2016 tested in parallel with LDAs).ResultsGenotype inclusivity and analytical specificity was 100%. However, ARIES was 0.5 log, 1–2logs and 2.5logs less sensitive for fluA, RSV and fluB respectively, compared to LDA. In total, 447 clinical samples were included, of which 15.4% tested positive for fluA, 9.2% for fluB and 26.0% for RSV, in both LDA and ARIES. ARIES clinical sensitivity compared to LDA was 98.6% (fluA), 93.3% (fluB) and 95.1% (RSV). Clinical specificity was 100% for all targets. ARIES detected 10.6% (4 fluA, 8 fluB, 11 RSV) and 26.9% (7 fluA, 3 fluB, 22 RSV) more samples compared to DFA and ICT, all confirmed by LDA.ConclusionAlthough analytically ARIES is less sensitive than LDA, the clinical performance of the assay in our tertiary care setting was comparable, and significantly better than that of the established rapid assays

Accretion Processes for General Spherically Symmetric Compact Objects

We investigate the accretion process for different spherically symmetric space-time geometries for a static fluid. We analyse this procedure using the most general black hole metric ansatz. After that, we examine the accretion process for specific spherically symmetric metrics obtaining the velocity of the sound during the process and the critical speed of the flow of the fluid around the black hole. In addition, we study the behaviour of the rate of change of the mass for each chosen metric for a barotropic fluid.Comment: 10 pages, 15 figures, v2 accepted for publication in 'European Physical Journal C

A phase I, dose-escalation study of volasertib combined with nintedanib in advanced solid tumors

Background: Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases. This study determined the maximum tolerated dose (MTD) and pharmacokinetics of volasertib combined with nintedanib, a potent and orally bioavailable triple angiokinase inhibitor, in patients with advanced solid tumors. Patients and methods: This open-label, dose-escalation trial recruited patients with advanced metastatic solid tumors following failure of conventional treatment (NCT01022853; Study 1230.7). Volasertib was administered by intravenous infusion over 2 h, starting at 100 mg in the first dose cohort. Nintedanib was administered orally at a dose of 200 mg twice daily. The first treatment cycle comprised 28 days (days 1-7 and days 9-28: nintedanib; day 8: volasertib). From cycle 2 onwards, volasertib was administered on day 1 of a 21-day cycle and nintedanib was administered days 2-21. The primary objective was the MTD of volasertib in combination with nintedanib. Results: Thirty patients were treated. The MTD of volasertib plus fixed-dose nintedanib was 300 mg once every 3 weeks, the same as the recommended single-agent dose of volasertib in solid tumors. Two of 12 assessable patients treated with the MTD experienced dose-limiting toxicities [grade 3 increased alanine aminotransferase (ALT); grade 3 ALT increase and grade 3 increased aspartate aminotransferase]. Disease control [stable disease (SD)/partial response (PR)/complete response (CR)] was achieved in 18 patients (60%): 1 CR (breast cancer), 1 PR (nonsmall-cell lung cancer), and 16 patients with SD. Volasertib showed that multiexponential pharmacokinetic behavior and co-administration of nintedanib had no significant effects on its exposure. Conclusions: Volasertib could be combined with fixed-dose nintedanib at the recommended single-agent dose. At this dose, the combination had a manageable safety profile without unexpected or overlapping adverse events, and showed antitumor activity

Mass-Varying Neutrinos from a Variable Cosmological Constant

We consider, in a completely model-independent way, the transfer of energy between the components of the dark energy sector consisting of the cosmological constant (CC) and that of relic neutrinos. We show that such a cosmological setup may promote neutrinos to mass-varying particles, thus resembling a recently proposed scenario of Fardon, Nelson, and Weiner (FNW), but now without introducing any acceleronlike scalar fields. Although a formal similarity of the FNW scenario with the variable CC one can be easily established, one nevertheless finds different laws for neutrino mass variation in each scenario. We show that as long as the neutrino number density dilutes canonically, only a very slow variation of the neutrino mass is possible. For neutrino masses to vary significantly (as in the FNW scenario), a considerable deviation from the canonical dilution of the neutrino number density is also needed. We note that the present `coincidence' between the dark energy density and the neutrino energy density can be obtained in our scenario even for static neutrino masses.Comment: 8 pages, minor corrections, two references added, to apear in JCA

Progress in the physics of massive neutrinos

The current status of the physics of massive neutrinos is reviewed with a forward-looking emphasis. The article begins with the general phenomenology of neutrino oscillations in vacuum and matter and documents the experimental evidence for oscillations of solar, reactor, atmospheric and accelerator neutrinos. Both active and sterile oscillation possibilities are considered. The impact of cosmology (BBN, CMB, leptogenesis) and astrophysics (supernovae, highest energy cosmic rays) on neutrino observables and vice versa, is evaluated. The predictions of grand unified, radiative and other models of neutrino mass are discussed. Ways of determining the unknown parameters of three-neutrino oscillations are assessed, taking into account eight-fold degeneracies in parameters that yield the same oscillation probabilities, as well as ways to determine the absolute neutrino mass scale (from beta-decay, neutrinoless double-beta decay, large scale structure and Z-bursts). Critical unknowns at present are the amplitude of \nu_\mu to \nu_e oscillations and the hierarchy of the neutrino mass spectrum; the detection of CP violation in the neutrino sector depends on these and on an unknown phase. The estimated neutrino parameter sensitivities at future facilities (reactors, superbeams, neutrino factories) are given. The overall agenda of a future neutrino physics program to construct a bottom-up understanding of the lepton sector is presented.Comment: 111 pages, 35 figures. Update

Author Correction: iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification

An amendment to this paper has been published and can be accessed via a link at the top of the paper.This work was partially funded by the projects NanoSTIMA and NORTE-01-0145-FEDER-000029, both supported by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF); and by the Portuguese Foundation for Science and Technology, within the scope of the PhD grant PD/BD/135023/2017 and the projects: PTDC/BBB-EBI/0567/2014 (to CAR) and UID/BIM/04293/2013. It was also funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; PPBI-POCI-01-0145-FEDER-022122). MB acknowledges the Marie Sklodowska-Curie grant agreement No. 748880

The FHI FEL Upgrade Design

Since coming on-line in November 2013, the Fritz-Haber-Institut (FHI) der Max-Planck-Gesellschaft (MPG) Free-Electron Laser (FEL) has provided intense, tunable infrared radiation to FHI user groups. It has enabled experiments in diverse fields ranging from bio-molecular spectroscopy to studies of clusters and nanoparticles, nonlinear solid-state spectroscopy, and surface science, resulting in 50 peer-reviewed publications so far. A significant upgrade of the FHI FEL is now being prepared. A second short Rayleigh range undulator FEL beamline is being added that will permit lasing from 160 microns. Additionally, a 500 MHz kicker cavity will permit simultaneous two-color operation of the FEL from both FEL beamlines over an optical range of 5 to 50 microns by deflecting alternate 1 GHz pulses into each of the two undulators. We will describe the upgraded FHI FEL physics and engineering design and present the plans for two-color FEL operations in November 2020

In Quest of Neutrino Masses at O{\cal{O}}(eV) Scale

Neutrino oscillation and tritium beta decay experiments taken simultaneously into account are able to access the so far imperceptible absolute neutrino masses at the electronvolt level. The neutrino mass spectrum derived in this way is independent of the nature of neutrinos (Dirac or Majorana). Furthermore, the lack of neutrinoless double beta decay gives additional constraints on the Majorana neutrino mass spectrum. A case of three neutrinos is examined. Influence of different solutions to the solar neutrino deficit problem on the results is discussed. Apart from the present situation, four qualitatively distinct experimental situations which are possible in the future are investigated: when the two decay experiments give only upper bounds on effective neutrino masses, when either one of them gives a positive result, and when both give positive results. The discussion is carried out by taking into account the present experimental errors of relevant neutrino parameters as well as their much more precise expected estimations (e.g. by $\nu$ factories). It is shown in which cases the upgraded decay experiments simultaneously with neutrino oscillation data may be able to fix the absolute scale of the neutrino mass spectrum, answer the question of the neutrino nature and put some light on CP phases in the lepton sector.Comment: 30 pages, 6 figs, to appear in PR

MiniBooNE and LSND data: non-standard neutrino interactions in a (3+1) scheme versus (3+2) oscillations

The recently observed event excess in MiniBooNE anti-neutrino data is in agreement with the LSND evidence for electron anti-neutrino appearance. We propose an explanation of these data in terms of a (3+1) scheme with a sterile neutrino including non-standard neutrino interactions (NSI) at neutrino production and detection. The interference between oscillations and NSI provides a source for CP violation which we use to reconcile different results from neutrino and anti-neutrino data. Our best fit results imply NSI at the level of a few percent relative to the standard weak interaction, in agreement with current bounds. We compare the quality of the NSI fit to the one obtained within the (3+1) and (3+2) pure oscillation frameworks. We also briefly comment on using NSI (in an effective two-flavour framework) to address a possible difference in neutrino and anti-neutrino results from the MINOS experiment.Comment: 28 pages, 9 figures, discussion improved, new appendix added, conclusions unchange