. Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K‐L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; ...Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012; 271: 193–203.
Objective. An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance.
Design. Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions.
Setting. Two managed care organizations in California.
Subjects. Number of 189 629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008.
Outcome. Potential new‐onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12‐month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC).
Results. Overall, 1014 potential new‐onset cases were electronically identified; 719 were eligible for case review; 31–40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto’s disease IRR = 1.29, 95% confidence interval: 1.08–1.56. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study.
Conclusions. No autoimmune safety signal was found in women vaccinated with HPV4.
We propose a unified interpretation for persistent coronal outflows and metric radio noise storms, two phenomena typically observed in association with quiescent solar active regions. Our ...interpretation is based on multi-wavelength observations of two such regions as they crossed the meridian in May and July 2007. For both regions, we observe a persistent pattern of blue-shifted coronal emission in high-temperature lines with Hinode/EIS, and a radio noise storm with the Nançay Radioheliograph. The observations are supplemented by potential and linear force-free extrapolations of the photospheric magnetic field over large computational boxes, and by a detailed analysis of the coronal magnetic field topology. We find true separatrices in the coronal field and null points high in the corona, which are preferential locations for magnetic reconnection and electron acceleration. We suggest that the continuous growth of active regions maintains a steady reconnection across the separatrices at the null point. This interchange reconnection occurs between closed, high-density loops in the core of the active region and neighbouring open, low-density flux tubes. Thus, the reconnection creates strong pressure imbalances which are the main drivers of plasma upflows. Furthermore, the acceleration of low-energy electrons in the interchange reconnection region sustains the radio noise storm in the closed loop areas, as well as weak type III emission along the open field lines. For both active regions studied, we find a remarkable agreement between the observed places of persistent coronal outflows and radio noise storms with their locations as predicted by our interpretation.
Aims.
We aim to constrain the acceleration, injection, and transport processes of flare-accelerated energetic electrons by comparing their characteristics at the Sun with those injected into ...interplanetary space.
Methods.
We have identified 17 energetic electron events well-observed with the SEPT instrument aboard STEREO which show a clear association with a hard X-ray (HXR) flare observed with the RHESSI spacecraft. We compare the spectral indices of the RHESSI HXR spectra with those of the interplanetary electrons. Because of the frequent double-power-law shape of the in situ electron spectra, we paid special attention to the choice of the spectral index used for comparison.
Results.
The time difference between the electron onsets and the associated type III and microwave bursts suggests that the electron events are detected at 1 AU with apparent delays ranging from 9 to 41 min. While the parent solar activity is clearly impulsive, also showing a high correlation with extreme ultraviolet jets, most of the studied events occur in temporal coincidence with coronal mass ejections (CMEs). In spite of the observed onset delays and presence of CMEs in the low corona, we find a significant correlation of about 0.8 between the spectral indices of the HXR flare and the in situ electrons. The correlations increase if only events with significant anisotropy are considered. This suggests that transport effects can alter the injected spectra leading to a strongly reduced imprint of the flare acceleration.
Conclusions.
We conclude that interplanetary transport effects must be taken into account when inferring the initial acceleration of solar energetic electron events. Although our results suggest a clear imprint of flare acceleration for the analyzed event sample, a secondary acceleration might be present which could account for the observed delays. However, the limited and variable pitch-angle coverage of SEPT could also be the reason for the observed delays.
Expectations of results from genome sequencing by end users are influenced by perceptions of uncertainty. This study aimed to assess uncertainties about sequencing by developing, evaluating, and ...implementing a novel scale. The Perceptions of Uncertainties in Genome Sequencing (PUGS) scale comprised ten items to assess uncertainties within three domains: clinical, affective, and evaluative. Participants (n=535) from the ClinSeq® NIH sequencing study completed a baseline survey that included the PUGS; responses (mean = 3.4/5, SD=0.58) suggested modest perceptions of certainty. A confirmatory factor analysis identified factor loadings that led to elimination of two items. A revised eight‐item PUGS scale was used to test correlations with perceived ambiguity (r = −0.303, p < 0.001), attitudinal ambivalence (r = −0.111, p = 0.011), and ambiguity aversion (r = −0.093, p = 0.033). Results support nomological validity. A correlation with the MICRA uncertainty subscale was found among 175 cohort participants who had received results (r = −0.335, p < 0.001). Convergent and discriminant validity were also satisfied in a second sample of 208 parents from the HudsonAlpha CSER Project who completed the PUGS (mean = 3.4/5, SD = 0.72), and configural invariance was supported across the two datasets. As such, the PUGS is a promising scale for evaluating perceived uncertainties in genome sequencing, which can inform interventions to help patients form realistic expectations of these uncertainties.
Solar energetic particle (SEP) events are related to flares and coronal mass ejections (CMEs). This work is a new investigation of statistical relationships between SEP peak intensities – deka-MeV ...protons and near-relativistic electrons – and characteristic quantities of the associated solar activity. We consider the speed of the CME and quantities describing the flare-related energy release: peak flux and fluence of soft X-ray (SXR) emission and the fluence of microwave emission. The sample comprises 38 SEP events associated with strong SXR bursts (classes M and X) in the western solar hemisphere between 1997 and 2006, in which the flare-related particle acceleration was accompanied by radio bursts indicating electron escape into the interplanetary space. The main distinction of the present statistical analysis from earlier work is that in addition to the classical Pearson correlation coefficient, the partial correlation coefficients are calculated to remove the correlation effects between the solar parameters themselves. The classical correlation analysis shows the usual picture of correlations with broad scatter between SEP peak intensities and the different parameters of solar activity and strong correlations between the solar activity parameters themselves. The partial correlation analysis shows that the only parameters that significantly affect the SEP intensity are the CME speed and the SXR fluence. The SXR peak flux and the microwave fluence make no additional contribution. We conclude that these findings bring statistical evidence that both flare acceleration and CME shock acceleration contribute to the deka-MeV proton and near-relativistic electron populations in large SEP events.
Observation and theory both reveal a close relationship between the kinematics of coronal mass ejections (CMEs) and the thermal energy release traced by the related soft X-ray (SXR) emission. A major ...problem of empirical studies of this relationship is the distortion of the CME speed by the projection effect in the coronagraphic measurements. We present a re-assessment of the statistical relationship between CME velocities and SXR parameters using the SOHO/LASCO catalog and GOES whole-Sun observations during the period 1996 to 2008. Forty-nine events were identified in which CMEs originated near the limb, at central meridian distances between 70
∘
and 85
∘
, and had a reliably identified SXR burst, the parameters of which – peak flux and fluence – could be determined with some confidence. We find similar correlations between the logarithms of CME speed and of SXR peak flux and fluence as several earlier studies, with correlation coefficients of 0.48 for the flux and 0.58 for the fluence. Correlations are slightly improved over an unrestricted CME sample when only limb events are used. However, a broad scatter persists. We derive the parameters of the CME–SXR relationship and use them to predict ICME arrival times at Earth. We show that the CME speed inferred from SXR fluence measurements tends to perform better than SoHO/LASCO measurements in predicting ICME arrival times near 1 AU. The estimation of the CME speed from SXR observations can therefore make a valuable contribution to space weather predictions.
We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In ...the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided. In this new version we continue to see the increasing overlap between immunodeficiency, as manifested by infection and/or malignancy, and immune dysregulation, as manifested by auto-inflammation, auto-immunity, and/or allergy. There is also an increased number of genetic defects that lead to susceptibility to specific organisms which reflects the finely tuned nature of immune defense systems. This classification is the most up to date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
The Energetic Particle Detector Rodríguez-Pacheco, J.; Wimmer-Schweingruber, R. F.; Mason, G. M. ...
Astronomy and astrophysics (Berlin),
10/2020, Letnik:
642
Journal Article
Recenzirano
After decades of observations of solar energetic particles from space-based observatories, relevant questions on particle injection, transport, and acceleration remain open. To address these ...scientific topics, accurate measurements of the particle properties in the inner heliosphere are needed. In this paper we describe the Energetic Particle Detector (EPD), an instrument suite that is part of the scientific payload aboard the Solar Orbiter mission. Solar Orbiter will approach the Sun as close as 0.28 au and will provide extra-ecliptic measurements beyond ∼30° heliographic latitude during the later stages of the mission. The EPD will measure electrons, protons, and heavy ions with high temporal resolution over a wide energy range, from suprathermal energies up to several hundreds of megaelectronvolts/nucleons. For this purpose, EPD is composed of four units: the SupraThermal Electrons and Protons (STEP), the Electron Proton Telescope (EPT), the Suprathermal Ion Spectrograph (SIS), and the High-Energy Telescope (HET) plus the Instrument Control Unit that serves as power and data interface with the spacecraft. The low-energy population of electrons and ions will be covered by STEP and EPT, while the high-energy range will be measured by HET. Elemental and isotopic ion composition measurements will be performed by SIS and HET, allowing full particle identification from a few kiloelectronvolts up to several hundreds of megaelectronvolts/nucleons. Angular information will be provided by the separate look directions from different sensor heads, on the ecliptic plane along the Parker spiral magnetic field both forward and backwards, and out of the ecliptic plane observing both northern and southern hemispheres. The unparalleled observations of EPD will provide key insights into long-open and crucial questions about the processes that govern energetic particles in the inner heliosphere.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA‐B*58:01 Genotype and Allopurinol Dosing was originally published in February 2013. We reviewed the recent literature ...and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplemental Material and included additional resources for applying CPIC guidelines into the electronic health record. Up‐to‐date information can be found at PharmGKB (http://www.pharmgkb.org).
Context.
On 2020 November 29, the first widespread solar energetic particle (SEP) event of solar cycle 25 was observed at four widely separated locations in the inner (≲1 AU) heliosphere. ...Relativistic electrons as well as protons with energies > 50 MeV were observed by Solar Orbiter (SolO), Parker Solar Probe, the Solar Terrestrial Relations Observatory (STEREO)-A and multiple near-Earth spacecraft. The SEP event was associated with an M4.4 class X-ray flare and accompanied by a coronal mass ejection and an extreme ultraviolet (EUV) wave as well as a type II radio burst and multiple type III radio bursts.
Aims.
We present multi-spacecraft particle observations and place them in context with source observations from remote sensing instruments and discuss how such observations may further our understanding of particle acceleration and transport in this widespread event.
Methods.
Velocity dispersion analysis (VDA) and time shift analysis (TSA) were used to infer the particle release times at the Sun. Solar wind plasma and magnetic field measurements were examined to identify structures that influence the properties of the energetic particles such as their intensity. Pitch angle distributions and first-order anisotropies were analyzed in order to characterize the particle propagation in the interplanetary medium.
Results.
We find that during the 2020 November 29 SEP event, particles spread over more than 230° in longitude close to 1 AU. The particle onset delays observed at the different spacecraft are larger as the flare–footpoint angle increases and are consistent with those from previous STEREO observations. Comparing the timing when the EUV wave intersects the estimated magnetic footpoints of each spacecraft with particle release times from TSA and VDA, we conclude that a simple scenario where the particle release is only determined by the EUV wave propagation is unlikely for this event. Observations of anisotropic particle distributions at SolO, Wind, and STEREO-A do not rule out that particles are injected over a wide longitudinal range close to the Sun. However, the low values of the first-order anisotropy observed by near-Earth spacecraft suggest that diffusive propagation processes are likely involved.
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