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This corrects the article DOI: 10.1103/PhysRevLett.130.211001.
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Detailed measurements of the spectral structure of cosmic-ray electrons and positrons from 10.6 GeV to 7.5 TeV are presented from over 7 years of observations with the CALorimetric Electron Telescope (CALET) on the International Space Station. The instrument, consisting of a charge detector, an imaging calorimeter, and a total absorption calorimeter with a total depth of 30 radiation lengths at normal incidence and a fine shower imaging capability, is optimized to measure the all-electron spectrum well into the TeV region. Because of the excellent energy resolution (a few percent above 10 GeV) and the outstanding e/p separation (10^{5}), CALET provides optimal performance for a detailed search of structures in the energy spectrum. The analysis uses data up to the end of 2022, and the statistics of observed electron candidates has increased more than 3 times since the last publication in 2018. By adopting an updated boosted decision tree analysis, a sufficient proton rejection power up to 7.5 TeV is achieved, with a residual proton contamination less than 10%. The observed energy spectrum becomes gradually harder in the lower energy region from around 30 GeV, consistently with AMS-02, but from 300 to 600 GeV it is considerably softer than the spectra measured by DAMPE and Fermi-LAT. At high energies, the spectrum presents a sharp break around 1 TeV, with a spectral index change from -3.15 to -3.91, and a broken power law fitting the data in the energy range from 30 GeV to 4.8 TeV better than a single power law with 6.9 sigma significance, which is compatible with the DAMPE results. The break is consistent with the expected effects of radiation loss during the propagation from distant sources (except the highest energy bin). We have fitted the spectrum with a model consistent with the positron flux measured by AMS-02 below 1 TeV and interpreted the electron+positron spectrum with possible contributions from pulsars and nearby sources. Above 4.8 TeV, a possible contribution from known nearby supernova remnants, including Vela, is addressed by an event-by-event analysis providing a higher proton-rejection power than a purely statistical analysis.
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We present the observation of a charge-sign dependent solar modulation of galactic cosmic rays (GCRs) with the Calorimetric Electron Telescope onboard the International Space Station over 6 yr, corresponding to the positive polarity of the solar magnetic field. The observed variation of proton count rate is consistent with the neutron monitor count rate, validating our methods for determining the proton count rate. It is observed by the Calorimetric Electron Telescope that both GCR electron and proton count rates at the same average rigidity vary in anticorrelation with the tilt angle of the heliospheric current sheet, while the amplitude of the variation is significantly larger in the electron count rate than in the proton count rate. We show that this observed charge-sign dependence is reproduced by a numerical "drift model" of the GCR transport in the heliosphere. This is a clear signature of the drift effect on the long-term solar modulation observed with a single detector.
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Radiação Cósmica , Voo Espacial , Telescópios , Prótons , ElétronsRESUMO
We present the results of a direct measurement of the cosmic-ray helium spectrum with the CALET instrument in operation on the International Space Station since 2015. The observation period covered by this analysis spans from October 13, 2015, to April 30, 2022 (2392 days). The very wide dynamic range of CALET allowed for the collection of helium data over a large energy interval, from â¼40 GeV to â¼250 TeV, for the first time with a single instrument in low Earth orbit. The measured spectrum shows evidence of a deviation of the flux from a single power law by more than 8σ with a progressive spectral hardening from a few hundred GeV to a few tens of TeV. This result is consistent with the data reported by space instruments including PAMELA, AMS-02, and DAMPE and balloon instruments including CREAM. At higher energy we report the onset of a softening of the helium spectrum around 30 TeV (total kinetic energy). Though affected by large uncertainties in the highest energy bins, the observation of a flux reduction turns out to be consistent with the most recent results of DAMPE. A double broken power law is found to fit simultaneously both spectral features: the hardening (at lower energy) and the softening (at higher energy). A measurement of the proton to helium flux ratio in the energy range from 60 GeV/n to about 60 TeV/n is also presented, using the CALET proton flux recently updated with higher statistics.
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The relative abundance of cosmic ray nickel nuclei with respect to iron is by far larger than for all other transiron elements; therefore it provides a favorable opportunity for a low background measurement of its spectrum. Since nickel, as well as iron, is one of the most stable nuclei, the nickel energy spectrum and its relative abundance with respect to iron provide important information to estimate the abundances at the cosmic ray source and to model the Galactic propagation of heavy nuclei. However, only a few direct measurements of cosmic-ray nickel at energy larger than â¼3 GeV/n are available at present in the literature, and they are affected by strong limitations in both energy reach and statistics. In this Letter, we present a measurement of the differential energy spectrum of nickel in the energy range from 8.8 to 240 GeV/n, carried out with unprecedented precision by the Calorimetric Electron Telescope (CALET) in operation on the International Space Station since 2015. The CALET instrument can identify individual nuclear species via a measurement of their electric charge with a dynamic range extending far beyond iron (up to atomic number Z=40). The particle's energy is measured by a homogeneous calorimeter (1.2 proton interaction lengths, 27 radiation lengths) preceded by a thin imaging section (3 radiation lengths) providing tracking and energy sampling. This Letter follows our previous measurement of the iron spectrum [1O. Adriani et al. (CALET Collaboration), Phys. Rev. Lett. 126, 241101 (2021).PRLTAO0031-900710.1103/PhysRevLett.126.241101], and it extends our investigation on the energy dependence of the spectral index of heavy elements. It reports the analysis of nickel data collected from November 2015 to May 2021 and a detailed assessment of the systematic uncertainties. In the region from 20 to 240 GeV/n our present data are compatible within the errors with a single power law with spectral index -2.51±0.07.
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We present the measurement of the energy dependence of the boron flux in cosmic rays and its ratio to the carbon flux in an energy interval from 8.4 GeV/n to 3.8 TeV/n based on the data collected by the Calorimetric Electron Telescope (CALET) during â¼6.4 yr of operation on the International Space Station. An update of the energy spectrum of carbon is also presented with an increase in statistics over our previous measurement. The observed boron flux shows a spectral hardening at the same transition energy E_{0}â¼200 GeV/n of the C spectrum, though B and C fluxes have different energy dependences. The spectral index of the B spectrum is found to be γ=-3.047±0.024 in the interval 25
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A precise measurement of the cosmic-ray proton spectrum with the Calorimetric Electron Telescope (CALET) is presented in the energy interval from 50 GeV to 60 TeV, and the observation of a softening of the spectrum above 10 TeV is reported. The analysis is based on the data collected during â¼6.2 years of smooth operations aboard the International Space Station and covers a broader energy range with respect to the previous proton flux measurement by CALET, with an increase of the available statistics by a factor of â¼2.2. Above a few hundred GeV we confirm our previous observation of a progressive spectral hardening with a higher significance (more than 20 sigma). In the multi-TeV region we observe a second spectral feature with a softening around 10 TeV and a spectral index change from -2.6 to -2.9 consistently, within the errors, with the shape of the spectrum reported by DAMPE. We apply a simultaneous fit of the proton differential spectrum which well reproduces the gradual change of the spectral index encompassing the lower energy power-law regime and the two spectral features observed at higher energies.
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The Calorimetric Electron Telescope (CALET), in operation on the International Space Station since 2015, collected a large sample of cosmic-ray iron over a wide energy interval. In this Letter a measurement of the iron spectrum is presented in the range of kinetic energy per nucleon from 10 GeV/n to 2.0 TeV/n allowing the inclusion of iron in the list of elements studied with unprecedented precision by space-borne instruments. The measurement is based on observations carried out from January 2016 to May 2020. The CALET instrument can identify individual nuclear species via a measurement of their electric charge with a dynamic range extending far beyond iron (up to atomic number Z=40). The energy is measured by a homogeneous calorimeter with a total equivalent thickness of 1.2 proton interaction lengths preceded by a thin (3 radiation lengths) imaging section providing tracking and energy sampling. The analysis of the data and the detailed assessment of systematic uncertainties are described and results are compared with the findings of previous experiments. The observed differential spectrum is consistent within the errors with previous experiments. In the region from 50 GeV/n to 2 TeV/n our present data are compatible with a single power law with spectral index -2.60±0.03.
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In this paper, we present the measurement of the energy spectra of carbon and oxygen in cosmic rays based on observations with the Calorimetric Electron Telescope on the International Space Station from October 2015 to October 2019. Analysis, including the detailed assessment of systematic uncertainties, and results are reported. The energy spectra are measured in kinetic energy per nucleon from 10 GeV/n to 2.2 TeV/n with an all-calorimetric instrument with a total thickness corresponding to 1.3 nuclear interaction length. The observed carbon and oxygen fluxes show a spectral index change of â¼0.15 around 200 GeV/n established with a significance >3σ. They have the same energy dependence with a constant C/O flux ratio 0.911±0.006 above 25 GeV/n. The spectral hardening is consistent with that measured by AMS-02, but the absolute normalization of the flux is about 27% lower, though in agreement with observations from previous experiments including the PAMELA spectrometer and the calorimetric balloon-borne experiment CREAM.
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BACKGROUND: Malnutrition may worsen clinical outcomes in stroke patients. Few malnutrition screening tools have been validated in the rehabilitation setting. The present study aimed to assess the concurrent and predictive validity of two malnutrition screening tools. METHODS: We retrospectively collected scores for the Mini Nutritional Assessment Short-Form (MNA-SF) and the Geriatric Nutritional Risk Index (GNRI) in consecutive stroke patients aged ≥65 years in a rehabilitation hospital. Concurrent validity was confirmed against the European Society for Clinical Nutrition and Metabolism diagnostic criteria for malnutrition (ESPEN-DCM). Malnutrition risk within the ESPEN-DCM process was assessed using the Malnutrition Universal Screening Tool. Cut-off values with maximum Youden index, and with sensitivity (Se) >90% and specificity (Sp) >50%, were defined as appropriate for identification and screening of malnutrition, respectively. The Functional Independence Measure and discharge destination were used to explore predictive validity. RESULTS: Overall, 420 patients were analysed. Of these, we included 125 patients in the malnutrition group and 295 in the non-malnutrition group based on the ESPEN-DCM. Cut-off values for the identification and screening of malnutrition were 5 (Se: 0.78; Sp: 0.85) and 7 (Se: 0.96; Sp: 0.57) for the MNA-SF; 92 (Se: 0.74; Sp: 0.84) and 98 (Se: 0.93; Sp: 0.50) for the GNRI, respectively. The GNRI predicted discharge to acute care hospital, whereas the MNA-SF did not predict all outcome measures. CONCLUSIONS: The MNA-SF and the GNRI have a fair concurrent validity in stroke patients, although lower cut-off values than currently used were required for the MNA-SF. The GNRI exhibits good predictive validity for discharge destination.
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Avaliação Geriátrica , Desnutrição/diagnóstico , Programas de Rastreamento/normas , Avaliação Nutricional , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Desnutrição/etiologia , Estado Nutricional , Valor Preditivo dos Testes , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular CerebralRESUMO
In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from -2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or -2.87±0.06 including solar modulation effects in the lower energy region) to -2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ.
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Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.
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Transtorno Bipolar/genética , Adulto , Proteínas de Ciclo Celular/genética , Citocinas/genética , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Japão/epidemiologia , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Herança Multifatorial/genética , Fatores de Transcrição NFI/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Extended results on the cosmic-ray electron + positron spectrum from 11 GeV to 4.8 TeV are presented based on observations with the Calorimetric Electron Telescope (CALET) on the International Space Station utilizing the data up to November 2017. The analysis uses the full detector acceptance at high energies, approximately doubling the statistics compared to the previous result. CALET is an all-calorimetric instrument with a total thickness of 30 X_{0} at normal incidence and fine imaging capability, designed to achieve large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum in the region below 1 TeV shows good agreement with Alpha Magnetic Spectrometer (AMS-02) data. In the energy region below â¼300 GeV, CALET's spectral index is found to be consistent with the AMS-02, Fermi Large Area Telescope (Fermi-LAT), and Dark Matter Particle Explorer (DAMPE), while from 300 to 600 GeV the spectrum is significantly softer than the spectra from the latter two experiments. The absolute flux of CALET is consistent with other experiments at around a few tens of GeV. However, it is lower than those of DAMPE and Fermi-LAT with the difference increasing up to several hundred GeV. The observed energy spectrum above â¼1 TeV suggests a flux suppression consistent within the errors with the results of DAMPE, while CALET does not observe any significant evidence for a narrow spectral feature in the energy region around 1.4 TeV. Our measured all-electron flux, including statistical errors and a detailed breakdown of the systematic errors, is tabulated in the Supplemental Material in order to allow more refined spectral analyses based on our data.
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OBJECTIVES: We aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose (18F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff. METHODS: Sixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining 18F-FDG accumulation were scanned by high-resolution PEM. At least 1 day after surgery, tumour extension was evaluated by three independent experienced readers and by binarized images from the specimen-PEM data. Intraoperative exposure of medical staff to 18F-FDG was measured. RESULTS: Specimen-PEM evaluations of binarized images and the three investigators detected all (100 %, 12/12) invasive lesions and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive value of the accumulated lesions was 74.4 % (29/39) for the binarized images and 82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen sections detected 100 % (2/2) of the margin-positive cases, also detected by both specimen-PEM evaluation methods with no false-positive margin cases. The mean exposure of the medical staff to 18F was 18 µSv. CONCLUSIONS: Specimen-PEM detected invasive and in situ lesions with high accuracy and allowable radiation exposure. KEY POINTS: ⢠Specimen-PEM detected invasive and in situ lesions with high accuracy. ⢠Specimen-PEM predicted complete resection with the same accuracy as frozen section analysis. ⢠Breast-conserving surgery after fluorodeoxyglucose injection was performed with low medical staff exposure.
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Neoplasias da Mama/diagnóstico , Fluordesoxiglucose F18/farmacologia , Mamografia/métodos , Mastectomia Segmentar/métodos , Tomografia por Emissão de Pósitrons/métodos , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Compostos Radiofarmacêuticos/farmacologiaRESUMO
A novel algorithm developed within muon radiography to localize objects or cavities hidden inside large material volumes was recently proposed by some of the authors (Bonechi et al. 2015 J. Instrum. 10, P02003 (doi:10.1088/1748-0221/10/02/P02003)). The algorithm, based on muon back projection, helps to estimate the three-dimensional position and the transverse extension of detected objects without the need for measurements from different points of view, which would be required to make a triangulation. This algorithm can now be tested owing to the availability of real data collected both in laboratory tests and from real-world measurements. The methodology and some test results are presented in this paper.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.
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Cosmic-ray muon radiography (muography), an imaging technique that can provide measurements of rock densities within the top few 100 m of a volcanic cone, has now achieved a spatial resolution of the order of 10 m in optimal detection conditions. Muography provides images of the top region of a volcano edifice with a resolution that is considerably better than that typically achieved with other conventional methods (i.e. gravimetric). We expect such precise measurements, to provide us with information on anomalies in the rock density distribution, which can be affected by dense lava conduits, low-density magma supply paths or the compression with the depth of the overlying soil. The MUon RAdiography of VESuvius (MURAVES) project is now in its final phase of construction and deployment. Up to four muon hodoscopes, each with a surface of roughly 1 m2, will be installed on the slope of Vesuvius and take data for at least 12 months. We will use the muographic profiles, combined with data from gravimetric and seismic measurement campaigns, to determine the stratigraphy of the lava plug at the bottom of the Vesuvius crater, in order to infer potential eruption pathways. While the MURAVES project unfolds, others are using emulsion detectors on Stromboli to study the lava conduits at the top of the volcano. These measurements are ongoing: they have completed two measurement campaigns and are now performing the first data analysis.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.
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First results of a cosmic-ray electron and positron spectrum from 10 GeV to 3 TeV is presented based upon observations with the CALET instrument on the International Space Station starting in October, 2015. Nearly a half million electron and positron events are included in the analysis. CALET is an all-calorimetric instrument with total vertical thickness of 30 X_{0} and a fine imaging capability designed to achieve a large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum over 30 GeV can be fit with a single power law with a spectral index of -3.152±0.016 (stat+syst). Possible structure observed above 100 GeV requires further investigation with increased statistics and refined data analysis.
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The effect of cisplatin-induced acute renal failure (ARF) on the function and expression of multidrug resistanceassociated proteins (MRPs) was evaluated in rats. Rats received an intraperitoneal injection of cisplatin (9 mg/kg), and the induction of ARF state with high plasma concentrations of indoxyl sulfate and creatinine was observed 72 h after cisplatin treatment. The function of MRPs in the liver, kidney and brain was evaluated by measuring the tissue accumulation and biliary excretion of 2,4-dintrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, in rats. The levels of MRP1-4 expression were evaluated by Western blot analysis. Effect of ARF plasma components on MRP function was also examined by using calcein acetoxymethyl ester (calcein-AM) in HepG2 cells. In ARF rats (72 h after cisplatin treatment), the accumulation of DNP-SG in the liver, kidney and brain was significantly higher than those in control and cisplatin-treated rats (1 h after treatment). In ARF rats, intrinsic biliary excretion clearance of DNP-SG, estimated by dividing the biliary excretion rate of DNP-SG with the liver concentration, was also significantly reduced, though the expression levels of MRP1-4 in the liver remained unchanged. ARF rat plasma (5%) significantly increased the accumulation of calcein, a MRP substrate, in HepG2 cells after application of calcein-AM. In conclusion, MRP function was found to be suppressed not only in the kidney but also in the liver and brain in cisplatin-induced ARF rats, possibly due to the accumulation of some MRP substrates/inhibitors in plasma.
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Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Injúria Renal Aguda/fisiopatologia , Animais , Antineoplásicos/administração & dosagem , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Cisplatino/administração & dosagem , Creatinina/metabolismo , Modelos Animais de Doenças , Células Hep G2 , Humanos , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR12 ) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case-control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC0-6 h ) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC0-6 h of ASV was significantly lower in haemodialysis patients (P = 0.012). SVR12 rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log10 HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.
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Antivirais/efeitos adversos , Antivirais/farmacocinética , Hepatite C Crônica/tratamento farmacológico , Imidazóis/efeitos adversos , Imidazóis/farmacocinética , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Insuficiência Renal/complicações , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Carbamatos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Imidazóis/administração & dosagem , Incidência , Isoquinolinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Pirrolidinas , Diálise Renal , Insuficiência Renal/terapia , Sulfonamidas/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
Cosmic-ray electrons and positrons are a unique probe of the propagation of cosmic rays as well as of the nature and distribution of particle sources in our Galaxy. Recent measurements of these particles are challenging our basic understanding of the mechanisms of production, acceleration, and propagation of cosmic rays. Particularly striking are the differences between the low energy results collected by the space-borne PAMELA and AMS-02 experiments and older measurements pointing to sign-charge dependence of the solar modulation of cosmic-ray spectra. The PAMELA experiment has been measuring the time variation of the positron and electron intensity at Earth from July 2006 to December 2015 covering the period for the minimum of solar cycle 23 (2006-2009) until the middle of the maximum of solar cycle 24, through the polarity reversal of the heliospheric magnetic field which took place between 2013 and 2014. The positron to electron ratio measured in this time period clearly shows a sign-charge dependence of the solar modulation introduced by particle drifts. These results provide the first clear and continuous observation of how drift effects on solar modulation have unfolded with time from solar minimum to solar maximum and their dependence on the particle rigidity and the cyclic polarity of the solar magnetic field.