ABSTRACT We conduct a multiwavelength continuum variability study of the Seyfert 1 galaxy NGC 5548 to investigate the temperature structure of its accretion disk. The 19 overlapping continuum light ...curves ( to ) combine simultaneous Hubble Space Telescope, Swift, and ground-based observations over a 180 day period from 2014 January to July. Light-curve variability is interpreted as the reverberation response of the accretion disk to irradiation by a central time-varying point source. Our model yields the disk inclination , temperature K at 1 light day from the black hole, and a temperature-radius slope ( ) of . We also infer the driving light curve and find that it correlates poorly with both the hard and soft X-ray light curves, suggesting that the X-rays alone may not drive the ultraviolet and optical variability over the observing period. We also decompose the light curves into bright, faint, and mean accretion-disk spectra. These spectra lie below that expected for a standard blackbody accretion disk accreting at .
Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the ...specific mortality.
Retrospective multinational study including SCN diagnosed between 1990 and 2014.
2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1).
After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN.
IRB 00006477.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine ...countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
We report two microlensing planet candidates discovered by the Korea Microlensing Telescope Network (KMTNet) survey in 2017. However, both events have the 2L1S/1L2S degeneracy, which is an obstacle ...to claiming the discovery of the planets with certainty unless the degeneracy can be resolved. For KMT-2017-BLG-0962, the degeneracy cannot be resolved. If the 2L1S solution is correct, KMT-2017-BLG-0962 might be produced by a super Jupiter-mass planet orbiting a mid-M-dwarf host star. For KMT-2017-BLG-1119, the light-curve modeling favors the 2L1S solution but higher-resolution observations of the baseline object tend to support the 1L2S interpretation rather than the planetary interpretation. This degeneracy might be resolved by a future measurement of the lens-source relative proper motion. This study shows that the problem of resolving 2L1S/1L2S degeneracy exists over a much wider range of conditions than those considered by the theoretical study of Gaudi (1998).
African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African ...American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.
Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic ...fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI.
We present a search for lepton-flavor-violating τ decays into three leptons (electrons or muons) using 782 fb−1 of data collected with the Belle detector at the KEKB asymmetric-energy e+e− collider. ...No evidence for these decays is observed and we set 90% confidence level upper limits on the branching fractions between 1.5×10−8 and 2.7×10−8.
Sialic acid sugar-carrying glycans, sialoglycans, are aberrantly expressed on many tumor cells and have emerged as potent regulatory molecules involved in creating a tumor-supportive ...microenvironment. Sialoglycans can be recognized by sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immunomodulatory receptors. Most mammalian Siglecs transmit inhibitory signals comparable with the immune checkpoint inhibitor programmed death protein 1 (PD-1), but some are activating. Recent studies have shown that tumor cells can exploit sialoglycan–Siglec interactions to modulate immune cell function, contributing to an immunosuppressive tumor microenvironment (TME). Interference with sialoglycan synthesis or sialoglycan–Siglec interactions might improve antitumor immunity. Many questions regarding specificity, signaling, and regulatory function of sialoglycan–Siglec interactions remain. We posit that sialoglycans and Siglecs present as potential glyco-immune ‘checkpoints’ for cancer immunotherapy.
Aberrant sialic acid sugar expression is commonly found in different cancer types and immune cells express immunomodulatory Siglec receptors that can recognize these sialic acids in humans and mice. Recently, high expression of Siglecs was found on several immune cells within the tumor microenvironment (TME).Recent studies, using human samples and mouse models, indicate that sialoglycan–Siglec interactions in the TME can suppress effector immune cell activity and modulate myeloid cell functions, thus contributing to tumor immune evasion and sustained tumor growth.The individual contribution of the 14 Siglec family members to immune evasion and their precise sialoglycan ligands in the TME remain to be elucidated.Sialoglycans and Siglecs might represent immune ‘checkpoints’ that should be further explored as potential targets for cancer immunotherapy.
Therapeutic guidelines have not yet been established for low-grade gastric adenomas/dysplasias (LGD), which have a low risk of progression to high-grade adenomas/dysplasias (HGD) or to invasive ...carcinomas. This study aimed to evaluate risk factors for HGD/carcinoma that indicate a need for resection in biopsy-proven LGD lesions.
In total, 236 LGD lesions from 208 consecutive patients treated with endoscopic resection (ER) were retrospectively studied between 2004 and 2008. The Vienna classification was used for histological diagnosis. A generalized estimating equation (GEE) logistic regression model was used for multivariate analysis.
Among the 236 LGD lesions, the final pathology diagnosed 9 (3.8 %) as invasive carcinoma (category 5), 71 (30.1 %) as HGD (category 4), 148 (62.7 %) as LGD (category 3), and 8 (3.4 %) as negative/indefinite for dysplasia (category 1/2). Lesions ≥ 1 cm were classified as HGD/carcinoma in 39.4 % of patients (65/165). Multivariate analysis indicated that size of ≥ 1 cm (OR 1.93 95 % CI, 1.06 - 3.52), depressed morphology (OR 3.81 95 % CI, 1.22 - 11.9), and erythema (OR 2.49 95 % CI, 1.31 - 4.72) were significantly associated with HGD/carcinoma. The OR increased to 47.6 (95 % CI, 4.27 - 530.65) when the risk factors were all positive. The sensitivity and negative predictive value for ≥ 1 risk factors were 93.8 % and 90.9 %, respectively. As the number of risk factors of a lesion increased, the specificity and positive predictive value also increased.
Endoscopic resection can be recommended if a low-grade dysplastic lesion has at least one of the following risk factors: depressed morphology, surface erythema, or a size of 1 cm or greater. For lesions that have none of the three risk factors, follow-up endoscopy is recommended.
Amide proton transfer‐weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different ...institutes, and there are no agreed‐on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi‐center trials in larger patient cohorts and, ultimately, routine clinical use.
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