Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos. We searched for neutrino emission using machine learning techniques applied to 10 years of data from the IceCube Neutrino Observatory. By comparing diffuse emission models to a background-only hypothesis, we identified neutrino emission from the Galactic plane at the 4.5σ level of significance. The signal is consistent with diffuse emission of neutrinos from the Milky Way but could also arise from a population of unresolved point sources.

Evidence for neutrino emission from the nearby active galaxy NGC 1068.

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.

Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory.

We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{µ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{µ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.

Accuracy and self-validation of automated bone age determination.

The BoneXpert method for automated determination of bone age from hand X-rays was introduced in 2009 and is currently running in over 200 hospitals. The aim of this work is to present version 3 of the method and validate its accuracy and self-validation mechanism that automatically rejects an image if it is at risk of being analysed incorrectly. The training set included 14,036 images from the 2017 Radiological Society of North America (RSNA) Bone Age Challenge, 1642 images of normal Dutch and Californian children, and 8250 images from Tübingen from patients with Short Stature, Congenital Adrenal Hyperplasia and Precocious Puberty. The study resulted in a cross-validated root mean square (RMS) error in the Tübingen images of 0.62 y, compared to 0.72 y in the previous version. The RMS error on the RSNA test set of 200 images was 0.45 y relative to the average of six manual ratings. The self-validation mechanism rejected 0.4% of the RSNA images. 121 outliers among the self-validated images of the Tübingen study were rerated, resulting in 6 cases where BoneXpert deviated more than 1.5 years from the average of the three re-ratings, compared to 72 such cases for the original manual ratings. The accuracy of BoneXpert is clearly better than the accuracy of a single manual rating. The self-validation mechanism rejected very few images, typically with abnormal anatomy, and among the accepted images, there were 12 times fewer severe bone age errors than in manual ratings, suggesting that BoneXpert could be safer than manual rating.

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ß≳0.8 and up to ß∼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.

eV-Scale Sterile Neutrino Search Using Eight Years of Atmospheric Muon Neutrino Data from the IceCube Neutrino Observatory.

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100 eV^{2}. The best-fit point is found to be at sin^{2}(2θ_{24})=0.10 and Δm_{41}^{2}=4.5 eV^{2}, which is consistent with the no sterile neutrino hypothesis with a p value of 8.0%.

Characteristics of the Diffuse Astrophysical Electron and Tau Neutrino Flux with Six Years of IceCube High Energy Cascade Data.

We report on the first measurement of the astrophysical neutrino flux using particle showers (cascades) in IceCube data from 2010-2015. Assuming standard oscillations, the astrophysical neutrinos in this dedicated cascade sample are dominated (∼90%) by electron and tau flavors. The flux, observed in the sensitive energy range from 16 TeV to 2.6 PeV, is consistent with a single power-law model as expected from Fermi-type acceleration of high energy particles at astrophysical sources. We find the flux spectral index to be γ=2.53±0.07 and a flux normalization for each neutrino flavor of ϕ_{astro}=1.66_{-0.27}^{+0.25} at E_{0}=100 TeV, in agreement with IceCube's complementary muon neutrino results and with all-neutrino flavor fit results. In the measured energy range we reject spectral indices γ≤2.28 at ≥3σ significance level. Because of high neutrino energy resolution and low atmospheric neutrino backgrounds, this analysis provides the most detailed characterization of the neutrino flux at energies below ∼100 TeV compared to previous IceCube results. Results from fits assuming more complex neutrino flux models suggest a flux softening at high energies and a flux hardening at low energies (p value ≥0.06). The sizable and smooth flux measured below ∼100 TeV remains a puzzle. In order to not violate the isotropic diffuse gamma-ray background as measured by the Fermi Large Area Telescope, it suggests the existence of astrophysical neutrino sources characterized by dense environments which are opaque to gamma rays.

Time-Integrated Neutrino Source Searches with 10 Years of IceCube Data.

This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1 TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.

Constraints on Minute-Scale Transient Astrophysical Neutrino Sources.

High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E^{-2.5} neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to <5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is <10^{52.5} erg. For a harder E^{-2.13} neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is <10^{52} erg. A hypothetical population of transient sources has to be more common than 10^{-5} Mpc^{-3} yr^{-1} (5×10^{-8} Mpc^{-3} yr^{-1} for the E^{-2.13} spectrum) to account for the complete astrophysical neutrino flux.

Measurement of Atmospheric Neutrino Oscillations at 6-56 GeV with IceCube DeepCore.

We present a measurement of the atmospheric neutrino oscillation parameters using three years of data from the IceCube Neutrino Observatory. The DeepCore infill array in the center of IceCube enables the detection and reconstruction of neutrinos produced by the interaction of cosmic rays in Earth's atmosphere at energies as low as ∼5 GeV. That energy threshold permits measurements of muon neutrino disappearance, over a range of baselines up to the diameter of the Earth, probing the same range of L/E_{ν} as long-baseline experiments but with substantially higher-energy neutrinos. This analysis uses neutrinos from the full sky with reconstructed energies from 5.6 to 56 GeV. We measure Δm_{32}^{2}=2.31_{-0.13}^{+0.11}×10^{-3} eV^{2} and sin^{2}θ_{23}=0.51_{-0.09}^{+0.07}, assuming normal neutrino mass ordering. These results are consistent with, and of similar precision to, those from accelerator- and reactor-based experiments.

Search for neutrinos from decaying dark matter with IceCube: IceCube Collaboration.

With the observation of high-energy astrophysical neutrinos by the IceCube Neutrino Observatory, interest has risen in models of PeV-mass decaying dark matter particles to explain the observed flux. We present two dedicated experimental analyses to test this hypothesis. One analysis uses 6 years of IceCube data focusing on muon neutrino 'track' events from the Northern Hemisphere, while the second analysis uses 2 years of 'cascade' events from the full sky. Known background components and the hypothetical flux from unstable dark matter are fitted to the experimental data. Since no significant excess is observed in either analysis, lower limits on the lifetime of dark matter particles are derived: we obtain the strongest constraint to date, excluding lifetimes shorter than 10 28 s at 90% CL for dark matter masses above 10 TeV .

Measurement of the ν µ energy spectrum with IceCube-79: IceCube Collaboration.

IceCube is a neutrino observatory deployed in the glacial ice at the geographic South Pole. The ν µ energy unfolding described in this paper is based on data taken with IceCube in its 79-string configuration. A sample of muon neutrino charged-current interactions with a purity of 99.5% was selected by means of a multivariate classification process based on machine learning. The subsequent unfolding was performed using the software Truee. The resulting spectrum covers an E ν -range of more than four orders of magnitude from 125 GeV to 3.2 PeV. Compared to the Honda atmospheric neutrino flux model, the energy spectrum shows an excess of more than 1.9 σ in four adjacent bins for neutrino energies E ν ≥ 177.8 TeV . The obtained spectrum is fully compatible with previous measurements of the atmospheric neutrino flux and recent IceCube measurements of a flux of high-energy astrophysical neutrinos.

Constraints on Ultrahigh-Energy Cosmic-Ray Sources from a Search for Neutrinos above 10 PeV with IceCube.

We report constraints on the sources of ultrahigh-energy cosmic rays (UHECRs) above 10^{9} GeV, based on an analysis of seven years of IceCube data. This analysis efficiently selects very high- energy neutrino-induced events which have deposited energies from 5×10^{5} GeV to above 10^{11} GeV. Two neutrino-induced events with an estimated deposited energy of (2.6±0.3)×10^{6} GeV, the highest neutrino energy observed so far, and (7.7±2.0)×10^{5} GeV were detected. The atmospheric background-only hypothesis of detecting these events is rejected at 3.6σ. The hypothesis that the observed events are of cosmogenic origin is also rejected at >99% CL because of the limited deposited energy and the nonobservation of events at higher energy, while their observation is consistent with an astrophysical origin. Our limits on cosmogenic neutrino fluxes disfavor the UHECR sources having a cosmological evolution stronger than the star formation rate, e.g., active galactic nuclei and γ-ray bursts, assuming proton-dominated UHECRs. Constraints on UHECR sources including mixed and heavy UHECR compositions are obtained for models of neutrino production within UHECR sources. Our limit disfavors a significant part of parameter space for active galactic nuclei and new-born pulsar models. These limits on the ultrahigh-energy neutrino flux models are the most stringent to date.

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 ν_{µ} or ν[over ¯]_{µ} 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}2θ_{24}≤0.02 at Δm^{2}∼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 |U_{e4}|^{2}.

Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

OBJECTIVE: To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. METHODS: A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. RESULTS: Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. CONCLUSIONS: Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.

Evidence for Astrophysical Muon Neutrinos from the Northern Sky with IceCube.

Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of ν(e) and ν(τ) charged-current and neutral-current (cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35,000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012. While this sample is composed primarily of neutrinos produced by cosmic ray interactions in Earth's atmosphere, the highest energy events are inconsistent with a hypothesis of solely terrestrial origin at 3.7σ significance. These neutrinos can, however, be explained by an astrophysical flux per neutrino flavor at a level of Φ(E(ν))=9.9(-3.4)(+3.9)×10(-19) GeV(-1) cm(-2) sr(-1) s(-1)(E(ν)/100 TeV(-2), consistent with IceCube's Southern-Hemisphere-dominated result. Additionally, a fit for an astrophysical flux with an arbitrary spectral index is performed. We find a spectral index of 2.2(-0.2)(+0.2), which is also in good agreement with the Southern Hemisphere result.

Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube.

A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013. We demonstrate consistency with the (fe:fµ:fτ)⊕≈(1:1:1)⊕ flavor ratio at Earth commonly expected from the averaged oscillations of neutrinos produced by pion decay in distant astrophysical sources. Limits are placed on nonstandard flavor compositions that cannot be produced by averaged neutrino oscillations but could arise in exotic physics scenarios. A maximally tracklike composition of (0:1:0)⊕ is excluded at 3.3σ, and a purely showerlike composition of (1:0:0)⊕ is excluded at 2.3σ.

Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube: IceCube Collaboration.

We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.

Experts' Opinion on the Prenatal Therapy of Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency - Guideline of DGKED in cooperation with DGGG (S1-Level, AWMF Registry No. 174/013, July 2015).

Purpose: This guideline of the German Society of Pediatric Endocrinology and Diabetology (DGKED) is designed to be experts' opinion on the current concept of prenatal therapy for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). Several scientific medical societies have also participated in the guideline. It aims to offer guidance to physicians when they counsel affected families about prenatal therapy. Methods: The experts commissioned by the medical societies developed a consensus in an informal process. The consensus was subsequently confirmed by the steering committees of the respective medical societies. Recommendations: Prenatal CAH therapy is an experimental therapy. We recommend designing and using standardized protocols for the prenatal diagnosis, therapy and long-term follow-up of women and children treated prenatally with dexamethasone. If long-term follow-up is not possible, then prenatal therapy should not be performed.