The Energetic Particle Instrument-Low Energy (EPI-Lo) experiment has detected several weak, low-energy (∼30-300 keV nucleon-1) solar energetic particle (SEP) events during its first two closest ...approaches to the Sun, providing a unique opportunity to explore the sources of low-energy particle acceleration. As part of the Parker Solar Probe (PSP) Integrated Science Investigation of the Sun (IS IS) suite, EPI-Lo was designed to investigate the physics of energetic particles; however, in the special lowest-energy "time-of-flight only" product used in this study, it also responds to solar photons in a subset of approximately sunward-looking apertures lacking special light-attenuating foils. During the first three perihelia, in a frame rotating with the Sun, PSP undergoes retrograde motion, covering a 17° heliographic longitudinal range three times during the course of the ∼11-day perihelion passes, permitting a unique spatial and temporal study into the location, correlation, and persistence of previously unmeasurable SEPs. We examine the signatures of these SEPs (during the first PSP perihelion pass only) and the connection to possible solar sources using remote observations from the Solar Dynamics Observatory (SDO), the Solar TErrestrial RElations Observatory (STEREO), and the ground-based Global Oscillation Network Group (GONG). The orientation of the Sun relative to STEREO, SDO, and GONG makes such identifications challenging, but we do have several candidates, including an equatorial coronal hole at a Carrington longitude of ∼335°. To analyze observations from EPI-Lo, which is a new type of particle instrument, we examine instrumental effects and provide a preliminary separation of the ion signal from the photon background.
Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either ...increased TGF-β activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-β signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative
mutations (
) or a loss-of-function mutation in
(
) have evidence of deregulated TGF-β signaling with increased regulatory T cells and total FOXP3 expression. These naturally occurring mutations, recapitulated in vitro, impair STAT3-ERBIN-SMAD2/3 complex formation and fail to constrain nuclear pSMAD2/3 in response to TGF-β. In turn, cell-intrinsic deregulation of TGF-β signaling is associated with increased functional IL-4Rα expression on naive lymphocytes and can induce expression and activation of the IL-4/IL-4Rα/GATA3 axis in vitro. These findings link increased TGF-β pathway activation in
and
patient lymphocytes with increased T helper type 2 cytokine expression and elevated IgE.
In a series of high performance diverted discharges on DIII-D, we demonstrate that strong negative triangularity (NT) shaping robustly suppresses all edge-localized mode (ELM) activity over a wide ...range of plasma conditions: ⟨n⟩=0.1-1.5×10^{20} m^{-3}, P_{aux}=0-15 MW, and |B_{t}|=1-2.2 T, corresponding to P_{loss}/P_{LH08}∼8. The full dataset is consistent with the theoretical prediction that magnetic shear in the NT edge inhibits access to ELMing H-mode regimes; all experimental pressure profiles are found to be at or below the infinite-n ballooning stability limit. Our present dataset also features edge pressure gradients in strong NT that are closer to an H-mode than a typical L-mode plasma, supporting the consideration of NT for reactor design.
ABSTRACT
We report on the masses (MWD), effective temperatures ($\rm{T_\mathrm{eff}}$), and secular mean accretion rates ($\langle \dot{M} \rangle$) of 43 cataclysmic variable (CV) white dwarfs, 42 ...of which were obtained from the combined analysis of their Hubble Space Telescope ultraviolet data with the parallaxes provided by the Early Third Data Release of the Gaia space mission, and one from the white dwarf gravitational redshift. Our results double the number of CV white dwarfs with an accurate mass measurement, bringing the total census to 89 systems. From the study of the mass distribution, we derive $\langle M_\mathrm{WD} \rangle = 0.81^{+0.16}_{-0.20}\, \mathrm{M_\odot }$, in perfect agreement with previous results, and find no evidence of any evolution of the mass with orbital period. Moreover, we identify five systems with MWD < 0.5 M⊙, which are most likely representative of helium-core white dwarfs, showing that these CVs are present in the overall population. We reveal the presence of an anticorrelation between the average accretion rates and the white dwarf masses for the systems below the $2\!-\!3\,$ h period gap. Since $\langle \dot{M} \rangle$ reflects the rate of system angular momentum loss, this correlation suggests the presence of an additional mechanism of angular momentum loss that is more efficient at low white dwarf masses. This is the fundamental concept of the recently proposed empirical prescription of consequential angular momentum loss (eCAML) and our results provide observational support for it, although we also highlight how its current recipe needs to be refined to better reproduce the observed scatter in $\rm{T_\mathrm{eff}}$ and $\langle \dot{M} \rangle$, and the presence of helium-core white dwarfs.
Abstract
We augment the heliospheric network of galactic cosmic ray (GCR) monitors using 2012–2017 penetrating radiation measurements from the New Horizons (NH) Pluto Energetic Particle Spectrometer ...Science Investigation (PEPSSI), obtaining intensities of ≳75 MeV particles. The new, predominantly GCR observations provide critical links between the Sun and Voyager 2 and Voyager 1 (V2 and V1), in the heliosheath and local interstellar medium (LISM), respectively. We provide NH, Advanced Composition Explorer (ACE), V2, and V1 GCR observations, using them to track solar cycle variations and short-term Forbush decreases from the Sun to the LISM, and to examine the interaction that results in the surprising, previously reported V1 LISM anisotropy episodes. To investigate these episodes and the hitherto unexplained lagging of associated in situ shock features at V1, propagating disturbances seen at ACE, NH, and V2 were compared to V1. We conclude that the region where LISM magnetic field lines drape around the heliopause is likely critical for communicating solar disturbance signals upstream of the heliosheath to V1. We propose that the anisotropy-causing physical process that suppresses intensities at ∼90° pitch angles relies on GCRs escaping from a single compression in the draping region, not on GCRs trapped between two compressions. We also show that NH suprathermal and energetic particle data from PEPSSI are consistent with the interpretation that traveling shocks and corotating interaction region (CIR) remnants can be distinguished by the existence or lack of Forbush decreases, respectively, because turbulent magnetic fields at local shocks inhibit GCR transport while older CIR structures reaching the outer heliosphere do not.
Investments in autism spectrum disorder (ASD) research, guided by the Interagency Autism Coordinating Committee (IACC), have focused disproportionately on etiology over a well-established stakeholder ...priority area: research to improve accessibility and quality of community-based services. This study analyzed National Institutes of Health ASD services research funding from 2008 to 2018 to examine funding patterns, evaluate the impact of IACC objectives, and identify future directions. Approximately 9% of total funds were allocated to services research. This investment remained relatively stable across time and lacked diversity across domains (e.g., area of focus, ages sampled, implementation strategies used). While advancements were observed, including increased prevalence of projects focused on adult samples and on dissemination/implementation and prevention areas, greater investment in service research is critically needed.
The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to ...environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.
Summary
Background
Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti‐fibrotic therapies are available; however, ...several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD.
Aim
To standardise definitions, diagnosis and treatment targets for anti‐fibrotic stricture therapies in Chron's disease.
Methods
An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting.
Results
Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre‐stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post‐prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24‐48 weeks is considered the appropriate endpoint in pharmacological trials.
Conclusions
Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.
The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients ...with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm.
To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research.
MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists.
English-language studies describing methods of diagnosis of ME/CFS and their accuracy.
Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus.
Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability.
Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations.
Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.
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