Combining intensive practice nurse counselling or brief general practitioner advice with varenicline for smoking cessation in primary care: study protocol of a pragmatic randomized controlled trial

Introduction: Combining behavioural support and pharmacotherapy is most effective for smoking cessation and recommended in clinical guidelines. Despite that smoking cessation assistance from the general practitioner can be effective, dissemination of clinical practice guidelines and efforts on upskilling has not lead to the routine provision of smoking cessation advice among general practitioners. Intensive counselling from the practice nurse could contribute to better smoking cessation rates in primary care. However, the effectiveness of intensive counselling from a practice nurse versus usual care from a general practitioner in combination with varenicline is still unknown. Materials and methods: A pragmatic randomized controlled trial was conducted comparing: (a) intensive individual counselling delivered by a practice nurse and (b) brief advice delivered by a general practitioner; both groups received 12-weeks of open-label varenicline. A minimum of 272 adult daily smoking participants were recruited and treated in their routine primary care setting. The primary outcome was defined as prolonged abstinence from weeks 9 to 26, biochemically validated by exhaled carbon monoxide. Data was analysed blinded according to the intention-to-treat principle and participants with missing data on their smoking status at follow-up were counted as smokers. Secondary outcomes included: one-year prolonged abstinence, short-term incremental cost-effectiveness, medication adherence, and baseline predictors of successful smoking cessation. Discussion: This trial is the first to provide scientific evidence on the effectiveness, cost-effectiveness, and potential mechanisms of action of intensive practice nurse counselling combined with varenicline under real-life conditions. This paper explains the methodology of the trial and discusses the pragmatic and/or explanatory design aspects

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa

Searches for sterile neutrinos with the IceCube detector

The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous nu(mu) or (nu) over bar (mu) disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3 + 1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin(2)2 theta(24) <= 0.02 at Delta m(2) similar to 0.3 eV(2) at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of vertical bar U-e4 vertical bar(2)

Lowering IceCube’s energy threshold for point source searches in the southern sky

Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current nu(mu) interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (similar to 100 TeV) starting event in the sample found that this event alone represents a 2.8 sigma deviation from the hypothesis that the data consists only of atmospheric background

Observation and Characterization of a Cosmic Muon Neutrino Flux from the Northern Hemisphere using six years of IceCube data

The IceCube Collaboration has previously discovered a high-energy astrophysical neutrino flux using neutrino events with interaction vertices contained within the instrumented volume of the IceCube detector. We present a complementary measurement using charged current muon neutrino events where the interaction vertex can be outside this volume. As a consequence of the large muon range the effective area is significantly larger but the field of view is restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have been analyzed using a likelihood approach based on the reconstructed muon energy and zenith angle. At the highest neutrino energies between 191 TeV and 8.3 PeV a significant astrophysical contribution is observed, excluding a purely atmospheric origin of these events at $5.6\,\sigma$ significance. The data are well described by an isotropic, unbroken power law flux with a normalization at 100 TeV neutrino energy of $\left(0.90^{+0.30}_{-0.27}\right)\times10^{-18}\,\mathrm{GeV^{-1}\,cm^{-2}\,s^{-1}\,sr^{-1}}$ and a hard spectral index of $\gamma=2.13\pm0.13$. The observed spectrum is harder in comparison to previous IceCube analyses with lower energy thresholds which may indicate a break in the astrophysical neutrino spectrum of unknown origin. The highest energy event observed has a reconstructed muon energy of $(4.5\pm1.2)\,\mathrm{PeV}$ which implies a probability of less than 0.005% for this event to be of atmospheric origin. Analyzing the arrival directions of all events with reconstructed muon energies above 200 TeV no correlation with known $\gamma$-ray sources was found. Using the high statistics of atmospheric neutrinos we report the currently best constraints on a prompt atmospheric muon neutrino flux originating from charmed meson decays which is below $1.06$ in units of the flux normalization of the model in Enberg et al. (2008).Comment: 20 pages, 21 figure

The contribution of Fermi-2LAC blazars to the diffuse TeV-PeV neutrino flux

The recent discovery of a diffuse cosmic neutrino flux extending up to PeV energies raises the question of which astrophysical sources generate this signal. One class of extragalactic sources which may produce such high-energy neutrinos are blazars. We present a likelihood analysis searching for cumulative neutrino emission from blazars in the 2nd Fermi-LAT AGN catalogue (2LAC) using an IceCube neutrino dataset 2009-12 which was optimised for the detection of individual sources. In contrast to previous searches with IceCube, the populations investigated contain up to hundreds of sources, the largest one being the entire blazar sample in the 2LAC catalogue. No significant excess is observed and upper limits for the cumulative flux from these populations are obtained. These constrain the maximum contribution of the 2LAC blazars to the observed astrophysical neutrino flux to be $27 \%$ or less between around 10 TeV and 2 PeV, assuming equipartition of flavours at Earth and a single power-law spectrum with a spectral index of $-2.5$. We can still exclude that the 2LAC blazars (and sub-populations) emit more than $50 \%$ of the observed neutrinos up to a spectral index as hard as $-2.2$ in the same energy range. Our result takes into account that the neutrino source count distribution is unknown, and it does not assume strict proportionality of the neutrino flux to the measured 2LAC $\gamma$-ray signal for each source. Additionally, we constrain recent models for neutrino emission by blazars.Comment: 18 pages, 22 figure

Neutrinos and Cosmic Rays Observed by IceCube

The core mission of the IceCube Neutrino observatory is to study the origin and propagation of cosmic rays. IceCube, with its surface component IceTop, observes multiple signatures to accomplish this mission. Most important are the astrophysical neutrinos that are produced in interactions of cosmic rays, close to their sources and in interstellar space. IceCube is the first instrument that measures the properties of this astrophysical neutrino flux, and constrains its origin. In addition, the spectrum, composition and anisotropy of the local cosmic-ray flux are obtained from measurements of atmospheric muons and showers. Here we provide an overview of recent findings from the analysis of IceCube data, and their implications on our understanding of cosmic rays.Comment: Review article, to appear in Advances in Space Research, special issue "Origins of Cosmic Rays

The IceCube Neutrino Observatory: Instrumentation and Online Systems

The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.Comment: 83 pages, 50 figures; updated with minor changes from journal review and proofin