Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis.

BACKGROUND: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses. METHODS: Eighty-six acute ON cases were randomized to receive phenytoin (4-6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL). RESULTS: Sixty-four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo - phenytoin was -44 pg/ml at 3 months (P = 0.019) and -27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and -1.6 pg/ml at 6 months (P = 0.766). CONCLUSIONS: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized.

Implications of a change in case definition and screening of asylum seekers for hepatitis B surveillance in Germany in 2015 and 2016.

Since 2015, the number of hepatitis B virus (HBV) cases increased substantially in Germany. In 2015, a more sensitive HBV case definition was introduced. This coincided with an asylum seeker influx with differing screening strategies. Information on the asylum seeker status has been collected since 09/2015. We investigated this increase to interpret HBV notification data in Germany. We compared HBV surveillance data from 2010-2013 (baseline) with 2015-2016, excluding 2014 due to beginning of asylum seeker influx. We estimated the excess above the mean case number (baseline) using Poisson regression and compared asylum seeker cases and the excess of cases with the unknown asylum seeker status. HBV cases increased from 1855 (mean baseline) to 3873 (2015) and 3466 (2016) with 1903 asylum seeker cases and 1099 excess-cases with the unknown asylum seeker status in 2015-2016. Cases only fulfilling the changed case definition increased from 60% (1119) in baseline to 81% (P < 0.01) in 2015-2016; 69% of asylum seeker cases and 61% of excess-cases were males <40 years compared to 27% (baseline) (P < 0.01). Changed case definition increased the number of cases in official statistics substantially. Demographic and geographical distributions suggest that screening of asylum seekers increased the case numbers even to a higher extent than surveillance data indicates.

Evaluation of the German surveillance system for hepatitis B regarding timeliness, data quality, and simplicity, from 2005 to 2014.

OBJECTIVES: Germany has a mandatory surveillance system for acute hepatitis B (AHB) with the Protection against Infection Act as the legal basis in place since 2001. An amendment was introduced in 2013. We aimed at evaluating the surveillance systems' performance regarding timeliness, data quality, and simplicity from 2005 to 2014 and at assessing the effect of the amendment on timeliness of AHB surveillance. STUDY DESIGN: This study is a trend analysis of surveillance data. METHODS: Aspects of simplicity versus complexity of the surveillance system were assessed by describing data flow, levels of reporting, and data management procedures. Data quality, in terms of data completeness, was evaluated by quantitative indicators, and timeliness was measured in days between different levels of the surveillance system, notification delay, and reporting delay. Trends over time in data quality were analyzed by logistic regression, while negative binomial regression was used to test for trend over time regarding mean notification and reporting delay. RESULTS: Between January 2005 and December 2014, a total of 22,549 AHB infections were reported at the national level. The data flow of the German AHB surveillance system showed structural characteristics of a complex system. Over the 10-year period, completeness of reporting sex, age, probable route of transmission, and hepatitis B virus (HBV) vaccination were 99%, 100%, 25%, and 73%, respectively. However, data quality decreased over the evaluation period. Although notification delay improved over time (incident rate ratio [IRR] = 0.95, 95% confidence interval [CI] = 0.95-0.96; P < 0.05), reporting delay improved only since the amendment (IRR = 0.76, 95% CI = 0.70-0.82; P < 0.05). In total, mean notification and reporting delay were 3.0 days and 14.3 days, respectively. CONCLUSIONS: The German AHB surveillance system is operating in a timely manner. Although timeliness improved over the evaluation period and the amendment to the Protection against Infection Act succeeded in reducing reporting time, data quality in terms of completeness of information decreased considerably. As improved data completeness is required to adequately design prevention activities, reasons for this decrease should further be explored.

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.

Structural cortical network reorganization associated with early conversion to multiple sclerosis.

Brain structural covariance networks (SCNs) based on pairwise statistical associations of cortical thickness data across brain areas reflect underlying physical and functional connections between them. SCNs capture the complexity of human brain cortex structure and are disrupted in neurodegenerative conditions. However, the longitudinal assessment of SCN dynamics has not yet been explored, despite its potential to unveil mechanisms underlying neurodegeneration. Here, we evaluated the changes of SCNs over 12 months in patients with a first inflammatory-demyelinating attack of the Central Nervous System and assessed their clinical relevance by comparing SCN dynamics of patients with and without conversion to multiple sclerosis (MS) over one year. All subjects underwent clinical and brain MRI assessments over one year. Brain cortical thicknesses for each subject and time point were used to obtain group-level between-area correlation matrices from which nodal connectivity metrics were obtained. Robust bootstrap-based statistical approaches (allowing sampling with replacement) assessed the significance of longitudinal changes. Patients who converted to MS exhibited significantly greater network connectivity at baseline than non-converters (p = 0.02) and a subsequent connectivity loss over time (p = 0.001-0.02), not observed in non-converters' network. These findings suggest SCN analysis is sensitive to brain tissue changes in early MS, reflecting clinically relevant aspects of the condition. However, this is preliminary work, indicated by the low sample sizes, and its results and conclusions should be treated with caution and confirmed with larger cohorts.

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.

T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses.

Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice. In several cases, ZIKV primed CD4 cells responded to homologous sequences from other viruses, including DENV1-4, WNV or YFV. However, cross-reactive responses could confer immune deviation - the response to the Env DENV4 p1 epitope in HLA-DR1 resulted in IL-17A immunity, often associated with exacerbated immunopathogenesis. This conservation of recognition across Flaviviruses, may encompass protective and/or pathogenic components and poses challenges to characterization of ZIKV protective immunity.

Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex.

AIMS: Indices of brain volume [grey matter, white matter (WM), lesions] are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology and demyelination. METHODS: Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (× 60) following stereological principles. Grey and WM demyelination was outlined on myelin basic protein immunostained sections, and expressed as percentages of cortex and WM respectively. RESULTS: In MS, the mean number of neurons was 14.9 ± 1.9 billion vs. 24.4 ± 2.4 billion in controls (P < 0.011), a 39% difference. The density of neurons was smaller by 28% (P < 0.001) and cortical volume by 26% (P = 0.1). Strong association was detected between number of neurons and cortical volume (P < 0.0001). Demyelination affected 40 ± 13% of the MS neocortex and 9 ± 12% of the WM, however, neither correlated with neuronal loss. Only weak association was detected between number of neurons and WM volume. CONCLUSION: Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS.

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 .

FLAIR* to visualize veins in white matter lesions: A new tool for the diagnosis of multiple sclerosis?

OBJECTIVE: To explore the potential of a post-processing technique combining FLAIR and T2* (FLAIR*) to distinguish between lesions caused by multiple sclerosis (MS) from cerebral small vessel disease (SVD) in a clinical setting. METHODS: FLAIR and T2* head datasets acquired at 3T of 25 people with relapsing MS (pwRMS) and ten with pwSVD were used. After post-processing, FLAIR* maps were used to determine the proportion of white matter lesions (WML) showing the 'vein in lesion' sign (VIL), a characteristic histopathological feature of MS plaques. Sensitivity and specificity of MS diagnosis were examined on the basis of >45% VIL+ and >60% VIL+ WML, and compared with current dissemination in space (DIS) MRI criteria. RESULTS: All pwRMS had >45% VIL+ WML (range 58-100%) whilst in pwSVD the proportion of VIL+ WML was significantly lower (0-64%; mean 32±20%). Sensitivity based on >45% VIL+ was 100% and specificity 80% whilst with >60% VIL+ as the criterion, sensitivity was 96% and specificity 90%. DIS criteria had 96% sensitivity and 40% specificity. CONCLUSION: FLAIR* enables VIL+ WML detection in a clinical setting, facilitating differentiation of MS from SVD based on brain MRI. KEY POINTS: • FLAIR* in a clinical setting allows visualization of veins in white matter lesions. • Significant proportions of MS lesions demonstrate a vein in lesion on MRI. • Microangiopathic lesions demonstrate a lower proportion of intralesional veins than MS lesions. • Intralesional vein-based criteria may complement current MRI criteria for MS diagnosis.

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.

Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome.

BACKGROUND: Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). OBJECTIVE: To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. METHODS: In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0-7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years. RESULTS: During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS ( R2 = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model ( R2 = 0.64). CONCLUSION: Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS.

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}.

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.

[Current epidemiology of tuberculosis in Germany]. / Aktuelle Epidemiologie der Tuberkulose in Deutschland.

BACKGROUND: In addition to malaria and HIV/AIDS, tuberculosis (TB) is one of the world's most important infectious diseases. Also in Germany tuberculosis still remains a relevant public health problem that needs special attention. OBJECTIVES: This article provides an overview of the tuberculosis epidemiology in Germany with emphasis on drug resistance and population groups that are predominantly affected. METHODS: Based on surveillance data provided in the notification system, the TB-situation in Germany is presented-particularly with respect to drug resistance, origin of patients (country of birth and nationality) and treatment outcome. RESULTS: Since 2009, the continuous decline in case numbers has slowed down and is now stagnating as observed in several other industrialized nations. Since 2007, the proportion of foreign-born patients has continuously increased and accounts for over half of all cases registered in Germany. Special attention deserves the current drug resistance situation: With a proportion of 3.4% in 2013, multidrug-resistant tuberculosis (MDR-TB) has increased significantly compared to the previous year (2.1%) and the rate is therefore higher than in many other European low-incidence countries. Particularly high levels of MDR-TB were observed among foreign-born patients originating from a former Soviet Union country. On average, treatment success was observed in 79% of the cases. Thus, Germany does not reach the WHO target of 85% treatment success. Stagnating case numbers together with the observed drug resistance trend clearly indicate the need for continued efforts in tuberculosis control in Germany including focused strategies for the most affected population groups.

Spinal cord grey matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), pathological studies have identified substantial demyelination and neuronal loss in the spinal cord grey matter (GM). However, there has been limited in vivo investigation of cord GM abnormalities and their possible functional effects using MRI combined with clinical evaluation. METHODS: We recruited healthy controls (HC) and people with a clinically isolated syndrome (CIS), relapsing remitting (RR) and secondary progressive (SP) MS. All subjects had 3 T spinal cord MRI with measurement of cord cross-sectional area and diffusion tensor imaging metrics in the GM and posterior and lateral column white matter tracts using region of interest analysis. Physical disability was assessed using the expanded disability status scale (EDSS) and motor components of the MS functional composite scale. We calculated differences between MS and HC using a ANOVA and associations with disability using linear regression. RESULTS: 113 people were included in this study: 30 controls, 21 CIS, 33 RR and 29 SPMS. Spinal cord radial diffusivity (RD), fractional anisotropy and mean diffusivity in the GM and posterior columns were significantly more abnormal in SPMS than in RRMS. Spinal cord GM RD (ß=0.33, p<0.01) and cord area (ß=-0.45, p<0.01) were independently associated with EDSS (R(2)=0.77); spinal cord GM RD was also independently associated with a 9-hole peg test (ß=-0.33, p<0.01) and timed walk (ß=-0.20, p=0.04). CONCLUSIONS: The study findings suggest that pathological involvement of the spinal cord GM contributes significantly to physical disability in relapse-onset MS and SPMS in particular.

Observation of high-energy astrophysical neutrinos in three years of IceCube data.

A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.