Observation of Seven Astrophysical Tau Neutrino Candidates with IceCube.

We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.

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.

Juvenile idiopathic arthritis of the knee: is contrast needed to score disease activity when using an augmented MRI protocol comprising PD-weighted sequences?

OBJECTIVE: To compare unenhanced versus enhanced knee joint magnetic resonance imaging (MRI) to assess disease activity of juvenile idiopathic arthritis (JIA). METHODS: Fifty-three knee joint MRI examinations were performed on a 3-Tesla system in 27 patients (age: 11.40 ± 3.61 years; 21 females, 6 males). MRI protocols comprised PD-weighted sequences in addition to the widely used standard protocol. JIA subgroups comprised oligoarticular arthritis (n = 16), extended oligoarthritis (n = 6), rheumatoid factor-negative polyarticular arthritis (n = 3), enthesitis-related arthritis (n = 1), and psoriatic arthritis (n = 1). MR images were retrospectively analyzed by 3 experienced radiologists in two readings, using JAMRIS (juvenile arthritis MRI scoring) system and a modified IPSG (international prophylaxis study group) classification. In the first reading session, only unenhanced MR images were evaluated. In a second reading session, all images before and after contrast medium application were included. In order to avoid bias, an interval of at least 2 weeks was set between the two readings. The clinical JADAS10 (juvenile arthritis disease activity score) was calculated including clinical assessment and laboratory workup and correlated with MRI scores. Statistical analysis comprised Pearson's correlation for correlating two scoring results of unenhanced and the enhanced MRI, intra-class correlation coefficient (ICC) for inter- and intra-reader agreement. Diagnostic accuracy was calculated using ROC (receiver operating characteristics) curve analysis. RESULTS: Inter-reader agreement determined by ICC for unenhanced and enhanced MRI scores for IPSG was moderate (0.65, 95% CI 0.51-0.76, and 0.62, 95% CI 0.48-0.75) and high for JAMRIS (0.83, 95% CI 0.75-0.89, and 0.82, 95% CI 0.74-0.89). Intra-reader agreement was good to very good for JAMRIS (0.85 95% CI 0.81-0.88, 0.87 95% CI 0.83-0.89 and 0.96 95% CI 0.92-0.98) and IPSG (0.76 95% CI 0.62-0.86, 0.86 95% CI 0.77-0.92 and 0.92 95% CI 0.86-0.96). Scores of unenhanced MRI correlated with contrast-enhanced MRI: JAMRIS (r = 0.97, R2 = 0.93, p < 0.01), modified IPSG (r = 0.95, R2 = 0.91, p < 0.01). When using JADAS10 as a reference standard, moderate accuracy for both unenhanced and enhanced MRI scores was noted: JAMRIS (AUC = 0.68, 95% CI 0.51-0.85, and AUC = 0.66, 95% 0.49-0.82), IPSG score (AUC = 0.68, 95% 0.50-0.86, and AUC = 0.61, 95% 0.41-0.81). CONCLUSIONS: Our results suggest that contrast agent application could be omitted in JIA patients with an augmented knee MRI protocol comprising PD-weighted sequence. KEY POINTS: • Unenhanced MRI can detect disease activity of the knee joint in patients with JIA with equally high accuracy compared to contrast-enhanced MRI. • The intra- and inter-reader agreement was high for unenhanced and enhanced MRI JAMRIS scores, which indicate relatively good applicability of the scoring system, even for less experienced readers. • When using the clinical JADAS10 as a reference standard for the detection of disease activity, moderate accuracy for both unenhanced and enhanced MRI scores, both JAMRIS and IPSG, was noted, which might be caused by the fact that the majority of patients had either no or minimal clinical disease activity.

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.

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.

[Analysis of referral diagnoses to the rheumatology department]. / Analyse der Zuweisungsdiagnose in die internistische Rheumatologie.

BACKGROUND: The initial presentation of patients with symptoms indicative of a rheumatic disease is in most cases not directly to a rheumatologist. This study evaluated the following questions: I. Which medical specialists refer patients to a department of rheumatology? II. Evaluation of the accordance of the presumptive referral diagnosis and the final diagnosis by a rheumatologist. METHODS: A total of 947 patients (279 men and 668 women) who initially presented to a university hospital for rheumatological diagnostics were included in the study. The referring medical specialist fields were identified. Furthermore, a kappa analysis was performed to evaluate the accordance of the presumptive referral diagnosis and the final diagnosis generated after a rheumatological evaluation of the patients. RESULTS: Of the referrals 73% were initiated by general practitioners or internists functioning as general practitioners. The other referrers were 5% specialists in internal medicine (excluding rheumatology), 4% orthopedic/trauma surgeons, 1% other surgeons and 4% other specialist fields. A rheumatological diagnosis was made in 58% of the patients and rheumatological inflammatory joint diseases (26%), collagenosis (14%) and vasculitides (5%) were the most frequently diagnoses. The accordance of the presumptive diagnosis of the general practitioners and the final diagnosis after rheumatological evaluation was a kappa coefficient of κ = 0.304. Lower kappa values were evaluated for orthopedic surgeons (κ = 0.277) and other specialists (κ = 0.200). CONCLUSION: The referrals to a rheumatology institution were frequently initiated by general practitioners and internists functioning as general practitioners. In this context the presumptive diagnosis of general practitioners showed a low accordance with the final rheumatological diagnosis. In contrast, a detailed presumptive diagnosis is desirable for optimal use of the limited resources for rheumatological care.

MRI of cystic fibrosis lung manifestations: sequence evaluation and clinical outcome analysis.

AIM: To evaluate different magnetic resonance imaging (MRI) sequences for diagnosis of pulmonary manifestations of cystic fibrosis (CF) in comparison to chest computed tomography (CT), including an extended outcome analysis. MATERIALS AND METHODS: Twenty-eight patients with CF (15 male, 13 female, mean age 30.5±9.4 years) underwent CT and MRI of the lung. MRI (1.5 T) included different T2- and T1-weighted sequences: breath-hold HASTE (half Fourier acquisition single shot turbo spin echo) and VIBE (volumetric interpolated breath-hold examination, before and after contrast medium administration) sequences and respiratory-triggered PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) sequences with and without fat signal suppression, and perfusion imaging. CT and MRI images were evaluated by the modified Helbich and the Eichinger scoring systems. The clinical follow-up analysis assessed pulmonary exacerbations within 24 months. RESULTS: The highest concordance to CT was achieved for the PROPELLER sequences without fat signal suppression (concordance correlation coefficient CCC of the overall modified Helbich score 0.93 and of the overall Eichinger score 0.93). The other sequences had the following concordance: PROPELLER with fat signal suppression (CCCs 0.91 and 0.92), HASTE (CCCs 0.87 and 0.89), VIBE (CCCs 0.84 and 0.85) sequences. In the outcome analysis, the combined MRI analysis of all five sequences and a specific MRI protocol (PROPELLER without fast signal suppression, VIBE sequences, perfusion imaging) reached similar correlations to the number of pulmonary exacerbations as the CT examinations. CONCLUSION: An optimum lung MRI protocol in patients with CF consists of PROPELLER sequences without fat signal suppression, VIBE sequences, and lung perfusion analysis to enable high diagnostic efficacy and outcome prediction.

Observation of the universal magnetoelectric effect in a 3D topological insulator.

The electrodynamics of topological insulators (TIs) is described by modified Maxwell's equations, which contain additional terms that couple an electric field to a magnetization and a magnetic field to a polarization of the medium, such that the coupling coefficient is quantized in odd multiples of α/4π per surface. Here we report on the observation of this so-called topological magnetoelectric effect. We use monochromatic terahertz (THz) spectroscopy of TI structures equipped with a semitransparent gate to selectively address surface states. In high external magnetic fields, we observe a universal Faraday rotation angle equal to the fine structure constant α=e2/2hc (in SI units) when a linearly polarized THz radiation of a certain frequency passes through the two surfaces of a strained HgTe 3D TI. These experiments give insight into axion electrodynamics of TIs and may potentially be used for a metrological definition of the three basic physical constants.

Application of groundwater thresholds for trace elements on percolation water: a case study on percolation water from Northern German lowlands.

The German insignificance thresholds (GFS) for groundwater, derived with an added risk approach, will soon be adopted as trigger values for percolation water entering groundwater. The physicochemical properties of the vadose zone differ considerably from those of groundwater, which may lead to difficulties in the applicability of groundwater-derived GFS to percolation water. To test the applicability of the GFS to percolation water regarding the concentration level and the field-scale variability, 46 sites in Northern Germany were sampled, including arable land, grassland, and forest, situated on three spatially dominant parent materials: sand, glacial loam, and loess. Concentrations of As, Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, Sb, Sn, V, Zn, and F were analyzed in percolation water from the transition between the unsaturated to the saturated zone. We compared median and 90th percentile values of the background concentrations with the GFS. In more than 10% of all samples, background concentrations of Cd, Co, Ni, V, or Zn exceeded the GFS. We evaluated the applicability of the GFS on field-scale medians of background concentrations taking field-scale interquartile distance and the bootstrap percentile confidence interval of the field scale median of trace element background concentrations into consideration. Statements about exceedance or nonexceedance of GFS values could only be made with acceptable statistical uncertainty (α ≤ 0.1) when operational median concentrations were about one third higher or lower than the corresponding GFS.

[Computer-assisted diagnostic procedure for multislice computed tomography for assessment of the pulmonary arterial circulation. Clinical relevance]. / Computerassistiertes Diagnoseverfahren für die Mehrschichtcomputertomographie zur Beurteilung der pulmonalarteriellen Strombahn. Klinische Bedeutung.

BACKGROUND: A recently developed CAD software which highlights intravascular thrombotic structures from multislice computed tomography (MSCT) data was tested regarding feasibility, interobserver reliability and effect on radiology reports. MATERIAL AND METHODS: The CAD system ImageChecker® CT-Lung was tested in a randomized double-blinded study on 160 MSCT datasets (standardized technical conditions) performed for suspected pulmonary embolism (PE). The CAD data and images were analyzed by three radiologists in an independent and blinded fashion. RESULTS: The data from all 160 cases could be analyzed and 604 CAD prompts were set. Using the CAD analysis significantly more PEs were found in the peripheral pulmonary arterial circulation than described in the initial report. In 38 cases the 3 radiologists in consensus scored the images with the CAD adjunct as PE positive in peripheral vessels, which were initially reported as negative. Despite differences in the evaluation between two radiologists the amended assessment of the imaging data using the CAD softwear was reliable. There was a significant correlation between D-dimer values and the number of embolic structures detected by the CAD analysis. CONCLUSION: The recently developed CAD system is a useful adjunct as second reader to detect subtle emboli in peripheral vessels of MSCT datasets.

New insights into peripartum cardiomyopathy using cardiac magnetic resonance imaging.

PURPOSE: The aim of this study was to evaluate a comprehensive cardiac magnetic resonance (MR) imaging approach in patients with peripartum cardiomyopathy (PPCM). The focus was on inflammatory myocardial changes. MATERIALS AND METHODS: Retrospective analysis of 12 cardiac MR examinations was performed in 6 patients with PPCM. The protocol comprised cine sequences for the determination of chamber sizes and function. T 2-weighted sequences for determination of edema (T 2 ratio), T 1-weighted images for measurement of early gadolinium enhancement ratio (EGER), and late gadolinium enhancement (LGE) sequences were used for tissue characterization. 5 examinations were performed during the acute stage, and 7 examinations were performed during the course of the disease. RESULTS: Initially, 3 of 5 patients presented with an elevated left ventricular end-diastolic volume (LVEDV); in one patient, the LVEDV was in the upper range. In 4 of 5 subjects, the left ventricular ejection fraction (LVEF) was decreased. The T 2 ratio and EGER values were initially elevated in all women. No LGE was detected in initial scans. In follow-up examinations, the LVEDV decreased and the LVEF increased in all patients. Tissue-characterizing parameters decreased to normal in all but 1 patient. 2 patients showing LGE did not present a favorable clinical course. CONCLUSION: Myocardial inflammation was detected in the acute stage of PPCM, which was mostly transient. In our small group, patients showing LGE had a non-favorable clinical course. Future studies should include tissue-characterizing parameters, such as T 2 ratio and EGER. Thus, further insights into pathophysiology can be gained and therapeutic effects can be measured in a more extensive manner.

The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder.

Cyclin-dependent kinase (CDK) 8 associates with cyclin C (CycC) and belongs to the CDK module of the Mediator of transcription, together with MED12 and MED13. CDK8 is involved in the regulation of mRNA transcription and was identified as a potent oncogene in colon cancerogenesis. We have solved the 2.2-Å crystal structure of CDK8/CycC in complex with sorafenib, an anti-cancer drug of clinical relevance. The CDK8 structure reveals a unique CycC recognition helix that explains the specificity of the CDK8/CycC pair and discrimination among the highly promiscuous binding in the CDK/cyclin family. In contrast to all CDKs, the CDK8 activation loop appears not to be phosphorylated. Based on the structure, we discuss an alternate mode of CDK8 activation to the general CDK activation by T-loop phosphorylation. Sorafenib binds to the catalytic cleft of CDK8. It displays a deep pocket binding mode and is the first small molecule to induce a DFG-out conformation in the CDK family, which is actually DMG-out in CDK8.

Diffusion-weighted imaging of hyperacute cerebral hypoglycemia.

BACKGROUND AND PURPOSE: Cerebral hypoglycemia can result in reversible metabolic brain insults and can be associated with impaired diffusion disturbances. Our aim was to evaluate possible changes in DWI of the human brain during hyperacute short-term severe hypoglycemia. MATERIALS AND METHODS: Ten individuals scheduled for a clinical IST were examined with DWI while the test was performed. Venous blood glucose was continuously measured, and sequential DWI sequences were performed without interruption. Hypoglycemia was terminated with intravenous glucose administration when glucose levels were at ≤2.0 mmol/L. RESULTS: Blood glucose levels were lowered to a mean nadir of 1.75 ± 0.38 mmol/L. No alterations of cerebral diffusion could be observed in any individuals on DWI. CONCLUSIONS: Hyperacute short-term severe hypoglycemia does not induce visible changes in DWI of the human brain.