ABSTRACT Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for ...neutrino events with deposited energies TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, -induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index −2.50 0.09 and a flux at 100 TeV of . Under the same assumptions, an unbroken power law with index −2 is disfavored with a significance of 3.8 (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 (p = 1.7%) if instead we compare the best fit to a spectrum with index −2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a e fraction of 0.18 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 (p = 0.014%).
The main cause for fluoropyrimidine-related toxicity is deficiency of the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). In 2020, the European Medicines Agency (EMA) recommended two ...methods for pre-treatment DPD deficiency testing in clinical practice: phenotyping using endogenous uracil concentration or genotyping for DPYD risk variant alleles. This study assessed the DPD testing implementation status in Europe before (2019) and after (2021) the release of the EMA recommendations.
The survey was conducted from 16 March 2022 to 31 July 2022. An electronic form with seven closed and three open questions was e-mailed to 251 professionals with DPD testing expertise of 34 European countries. A descriptive analysis was conducted.
We received 79 responses (31%) from 23 countries. Following publication of the EMA recommendations, 87% and 75% of the countries reported an increase in the amount of genotype and phenotype testing, respectively. Implementation of novel local guidelines was reported by 21 responders (27%). Countries reporting reimbursement of both tests increased in 2021, and only four (18%) countries reported no coverage for any testing type. In 2019, major implementation drivers were ‘retrospective assessment of fluoropyrimidine-related toxicity’ (39%), and in 2021, testing was driven by ‘publication of guidelines’ (40%). Although the major hurdles remained the same after EMA recommendations—‘lack of reimbursement’ (26%; 2019 versus 15%; 2021) and ‘lack of recognizing the clinical relevance by medical oncologists’ (25%; 2019 versus 8%; 2021)—the percentage of specialists citing these decreased. Following EMA recommendations, 25% of responders reported no hurdles at all in the adoption of the new testing practice in the clinics.
The EMA recommendations have supported the implementation of DPD deficiency testing in Europe. Key factors for successful implementation were test reimbursement and clear clinical guidelines. Further efforts to improve the oncologists’ awareness of the clinical relevance of DPD testing in clinical practice are needed.
•EMA recommendations regarding pre-treatment DPD testing have supported the widespread implementation of testing in Europe.•Key factors for successful implementation of DPD testing are test reimbursement and existence of clear clinical guidelines.•Knowledge about the clinical applicability of pharmacogenetics among clinicians should be further improved.
We present results from an analysis looking for dark matter annihilation in the Sun with the IceCube neutrino telescope. Gravitationally trapped dark matter in the Sun’s core can annihilate into ...Standard Model particles making the Sun a source of GeV neutrinos. IceCube is able to detect neutrinos with energies >100 GeV while its low-energy infill array DeepCore extends this to >10 GeV. This analysis uses data gathered in the austral winters between May 2011 and May 2014, corresponding to 532 days of livetime when the Sun, being below the horizon, is a source of up-going neutrino events, easiest to discriminate against the dominant background of atmospheric muons. The sensitivity is a factor of two to four better than previous searches due to additional statistics and improved analysis methods involving better background rejection and reconstructions. The resultant upper limits on the spin-dependent dark matter-proton scattering cross section reach down to
1.46
×
10
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5
pb for a dark matter particle of mass 500 GeV annihilating exclusively into
τ
+
τ
-
particles. These are currently the most stringent limits on the spin-dependent dark matter-proton scattering cross section for WIMP masses above 50 GeV.
We present results on searches for point-like sources of neutrinos using four years of IceCube data, including the first year of data from the completed 86 string detector. The total livetime of the ...combined data set is 1373 days. For an E super(-2) spectrum, the observed 90% C.L. flux upper limits are ~10 super(-12) TeV super(-1) cm super(-2) s super(-1) for energies between 1 TeV and 1 PeV in the northern sky and ~10 super(-11) TeV super(-1) cm super(-2) s super(-1) for energies between 100 TeV and 100 PeV in the southern sky. This represents a 40% improvement compared to previous publications, resulting from both the additional year of data and the introduction of improved reconstructions. In addition, we present the first results from an all-sky search for extended sources of neutrinos. We update the results of searches for neutrino emission from stacked catalogs of sources and test five new catalogs; two of Galactic supernova remnants and three of active galactic nuclei. In all cases, the data are compatible with the background-only hypothesis, and upper limits on the flux of muon neutrinos are reported for the sources considered.
OBJECTIVE: To evaluate the significance of NR5A1 mutations in a large, well-phenotyped cohort of women with primary ovarian insufficiency (POI). Mutations in the NR5A1 gene (SF-1) were previously ...described in disorders of sexual development and adrenal insufficiency. Recently, a high frequency of NR5A1 gene mutations was reported in a small group of women with POI. DESIGN: Cross-sectional cohort study. SETTING: University hospital. PATIENT(S): Well-phenotyped women (n = 386) with secondary amenorrhea and diagnosed with POI, including women with familial POI (n = 77). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The entire coding region and splice sites of the NR5A1 gene were PCR-amplified and sequenced. The pathogenicity of identified mutations was predicted in silico by assessing Align-GVGD class and Grantham score. RESULT(S): Sequencing was successful in 356 patients with POI. In total, 9 mutations were identified in 10 patients. Five of these mutations concerned novel nonconservative mutations occurring in 5 patients. Prediction of effect on protein function showed low to intermediate pathogenicity for all nonconservative mutations. The overall NR5A1 gene mutation rate was 1.4%. CONCLUSION(S): The current study demonstrates that mutations in the NR5A1 gene are rare in women with POI. Primary ovarian insufficiency remains unexplained in the great majority of patients; therefore, continued efforts are needed to elucidate its underlying genetic factors.
ABSTRACT We present constraints derived from a search of four years of IceCube data for a prompt neutrino flux from gamma-ray bursts (GRBs). A single low-significance neutrino, compatible with the ...atmospheric neutrino background, was found in coincidence with one of the 506 observed bursts. Although GRBs have been proposed as candidate sources for ultra-high-energy cosmic rays, our limits on the neutrino flux disfavor much of the parameter space for the latest models. We also find that no more than ∼1% of the recently observed astrophysical neutrino flux consists of prompt emission from GRBs that are potentially observable by existing satellites.
Purpose We hypothesize that carpal-metacarpal (CMC) instability after carpal boss wedge excision is not caused only by damage to the dorsal ligament but mainly depends on the depth of the bony ...resection. Methods To test our hypothesis, this study analyzes the effect of wedge excisions with different depths (0, 15%, 35%, 55% of the third CMC joint) and the effect of different forces (0, 50, 100 N·m) on the stability (measured as the passive flexion) of the third CMC joint using 12 fresh-frozen human cadaver wrists. The passive flexion is defined as the increase in angular motion of the third CMC joint and represents change in stability during flexion of the joint. Results The results show that the mean passive flexion measured in the wedge excisions of 15% and 35% of the joint did not differ from that of neutral controls. Joints analyzed after a 55% wedge excision showed a significant increase in angular motion (increased passive flexion). This relates to the 50 N·m as well as the 100 N·m loaded test position. Conclusions This study shows that a wedge excision of clinically applicable depth of 35% does not create instability during flexion of the third CMC joint when loaded with physiologically relevant forces. Yet an extended and hardly clinically relevant 55% wedge excision results in a change in stability of the joint. To prevent instability when performing a wedge excision for symptomatic carpal boss, care must be taken to avoid excisions that exceed 35% of the third CMC joint.
We present a search for a neutrino signal from dark matter self-annihilations in the Milky Way using the IceCube Neutrino Observatory (IceCube). In 1005 days of data we found no significant excess of ...neutrinos over the background of neutrinos produced in atmospheric air showers from cosmic ray interactions. We derive upper limits on the velocity averaged product of the dark matter self-annihilation cross section and the relative velocity of the dark matter particles
⟨
σ
A
v
⟩
. Upper limits are set for dark matter particle candidate masses ranging from 10 GeV up to 1 TeV while considering annihilation through multiple channels. This work sets the most stringent limit on a neutrino signal from dark matter with mass between 10 and 100 GeV, with a limit of
1.18
·
10
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23
cm
3
s
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1
for 100 GeV dark matter particles self-annihilating via
τ
+
τ
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to neutrinos (assuming the Navarro–Frenk–White dark matter halo profile).
ABSTRACT In this paper searches for flaring astrophysical neutrino sources and sources with periodic emission with the IceCube neutrino telescope are presented. In contrast to time-integrated ...searches, where steady emission is assumed, the analyses presented here look for a time-dependent signal of neutrinos using the information from the neutrino arrival times to enhance the discovery potential. A search was performed for correlations between neutrino arrival times and directions, as well as neutrino emission following time-dependent light curves, sporadic emission, or periodicities of candidate sources. These include active galactic nuclei, soft γ-ray repeaters, supernova remnants hosting pulsars, microquasars, and X-ray binaries. The work presented here updates and extends previously published results to a longer period that covers 4 years of data from 2008 April 5 to 2012 May 16, including the first year of operation of the completed 86 string detector. The analyses did not find any significant time-dependent point sources of neutrinos, and the results were used to set upper limits on the neutrino flux from source candidates.
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