In December 2019, a new coronavirus known as 2019-nCoV emerged in Wuhan, China. The virus has spread globally and the infection was declared pandemic in March 2020. Although most cases of coronavirus ...disease 2019 (COVID-19) are mild, some of them rapidly develop acute respiratory distress syndrome. In the clinical management, chest X-rays (CXR) are essential, but the evaluation of COVID-19 CXR could be a challenge. In this context, we developed
COVID-19 TRAINING
, a free Web application for training on the evaluation of COVID-19 CXR. The application included 196 CXR belonging to three categories:
non-pathological
,
pathological compatible with COVID-19
, and
pathological non-compatible with COVID-19
. On the training screen, images were shown to the users and they chose a diagnosis among those three possibilities. At any time, users could finish the training session and be evaluated through the estimation of their diagnostic accuracy values: sensitivity, specificity, predictive values, and global accuracy. Images were hand-labeled by four thoracic radiologists. Average values for sensitivity, specificity, and global accuracy were .72, .64, and .68. Users who achieved better sensitivity registered less specificity (
p
< .0001) and those with higher specificity decreased their sensitivity (
p
< .0001). Users who sent more answers achieved better accuracy (
p
= .0002). The application
COVID-19 TRAINING
provides a revolutionary tool to learn the necessary skills to evaluate COVID-19 on CXR. Diagnosis training applications could provide a new original manner of evaluation for medical professionals based on their diagnostic accuracy values, and an efficient method to collect valuable data for research purposes.
To compare the in vivo uptake of two amyloid-binding PET agents, PIB and FDDNP, in human subjects with a prion protein (PrP) gene (PRNP) mutation that produces a clinical syndrome similar to ...Alzheimer disease (AD).
Amyloid imaging with specific PET ligands offers great promise for early detection and differential diagnosis of AD. Genetic forms of prion disease can present with clinical features that resemble AD, and at autopsy may show deposition of mutant PrP-amyloid. FDDNP binds to PrP-amyloid in postmortem human specimens, but has not been reported in vivo in prion disease. The ability of PIB to bind PrP-amyloid is not known.
Two brothers with a 6 octapeptide repeat insertion mutation (6-OPRI) in the PRNP gene underwent clinical, structural MRI, and FDG-PET evaluations. One brother received a PIB-PET evaluation, while the other received an FDDNP-PET scan. PET results were compared with five normal subjects and five individuals with AD scanned with either agent.
PIB uptake was similar to controls in one brother, while FDDNP uptake was intermediate between AD and controls in the other brother.
Different amyloid-binding agents may have differential sensitivity to prion-related brain pathology. A combination of amyloid imaging agents may be useful in the diagnosis of early-onset dementia.
Abstract
We study the broadband emission of Mrk 501 using multiwavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi's Large Area ...Telescope (LAT), NuSTAR, Swift, GASP-WEBT, and the Owens Valley Radio Observatory. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wave bands, with the highest occurring at X-rays and very-high-energy (VHE)
γ
-rays. A significant correlation (>3
σ
) between X-rays and VHE
γ
-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between the Swift X-Ray Telescope and Fermi-LAT. We additionally find correlations between high-energy
γ
-rays and radio, with the radio lagging by more than 100 days, placing the
γ
-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE
γ
-rays from mid-2017 to mid-2019 with a stable VHE flux (>0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2 yr long low state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED toward the low state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock.
Galaxy clusters are being assembled today in the most energetic phase of hierarchical structure formation which manifests itself in powerful shocks that contribute to a substantial energy density of ...cosmic rays (CRs). Hence, clusters are expected to be luminous gamma-ray emitters since they also act as energy reservoirs for additional CR sources, such as active galactic nuclei and supernova-driven galactic winds. To detect the gamma-ray emission from CR interactions with the ambient cluster gas, we conducted the deepest to date observational campaign targeting a galaxy cluster at very high-energy gamma-rays and observed the Perseus cluster with the MAGIC Cherenkov telescopes for a total of ~85 h of effective observing time. This campaign resulted in the detection of the central radio galaxy NGC 1275 at energies E > 100 GeV with a very steep energy spectrum. Here, we restrict our analysis to energies E > 630 GeV and detect no significant gamma-ray excess. This constrains the average CR-to-thermal pressure ratio to be ≲1–2%, depending on assumptions and the model for CR emission. Comparing these gamma-ray upper limits to models inferred from cosmological cluster simulations that include CRs constrains the maximum CR acceleration efficiency at structure formation shocks to be <50%.Alternatively, this may argue for non-negligible CR transport processes such as CR streaming and diffusion into the outer cluster regions. Finally, we derive lower limits on the magnetic field distribution assuming that the Perseus radio mini-halo is generated by secondary electrons/positrons that are created in hadronic CR interactions: assuming a spectrum of E-2.2 around TeV energies as implied by cluster simulations, we limit the central magnetic field to be >4–9 μG, depending on the rate of decline of the magnetic field strength toward larger radii. This range is well below field strengths inferred from Faraday rotation measurements in cool cores. Hence, the hadronic model remains a plausible explanation of the Perseus radio mini-halo.
This paper seeks contribute to the literature on the formation of consumer-based destination brand equity (CBDBE), on the premise that positioning is a major source of competitive advantage for ...organizations, coupled with an effective strategy to communicate that positioning. The aims of the study are: (1) to examine which type of positioning (specialized vs. diversified) is best suited to generating greater CBDBE, and (2) to identify the extent to which message consistency (high vs. low) within the integrated marketing communications strategy for the destination moderates that relationship. The results of the study make a contribution to the specialist literature on brand destination and integrated marketing communications, and offer interesting implications for tourist destination managers seeking to ensure their destination is selected by tourists.
•A positioning strategy based on tourism type has a significant effect on CBDBE.•Communication that comprises highly consistent messages contributes to increasing CBDBE.•Message consistency moderates the relationship between positioning strategy and CBDBE.
Context. 3C 279, the first quasar discovered to emit VHE γ-rays by the MAGIC telescope in 2006, was reobserved by MAGIC in January 2007 during a major optical flare and from December 2008 to April ...2009 following an alert from the Fermi space telescope on an exceptionally high γ-ray state. Aims. The January 2007 observations resulted in a detection on January 16 with significance 5.4σ, corresponding to a F (>150 GeV) (3.8 ± 0.8) × 10-11 ph cm-2 s-1 while the overall data sample does not show significant signal. The December 2008–April 2009 observations did not detect the source. We study the multiwavelength behaviour of the source at the epochs of MAGIC observations, collecting quasi-simultaneous data at optical and X-ray frequencies and for 2009 also γ-ray data from Fermi. Methods. We study the light curves and spectral energy distribution of the source. The spectral energy distributions of three observing epochs (including the February 2006, which has been previously published) are modelled with one-zone inverse Compton models and the emission on January 16, 2007 also with two zone model and with a lepto-hadronic model. Results. We find that the VHE γ-ray emission detected in 2006 and 2007 challenges standard one-zone model, based on relativistic electrons in a jet scattering broad line region photons, while the other studied models fit the observed spectral energy distribution more satisfactorily.
BackgroundBelimumab (BLM) is a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor. It is commonly used for treatment of systemic lupus erythematosus (SLE) patients ...with inadequate control to first-line treatments and inability to taper GC daily dose to acceptable levels. More recently it has been approved for patients with active lupus nephritis.ObjectivesTo report baseline profile of SLE patients treated with BLM enrolled in a SLE Spanish registry.MethodsMulticenter retrospective and longitudinal cohort study including SLE patients treated with BLM in 18 Spanish rheumatology units. Demographic, clinical data and treatments were collected at baseline, 6, 12 months and in the last visit available. Patients starting BLM in different periods (2010-2015 and 2016-2021) were compared regarding the reason of prescription of the drug.Results324 patients (91% female, 84,8% caucasian) were enrolled. Mean (±SD) age at diagnosis: 31.8 years (±11.9); mean disease duration of 8.7 years (±9.07) and mean follow-up 3.8 (±2.7). A total of 319 (98.45%) subjects met SLE 1997 ACR or SLICC 2012 criteria; 217 (68.2%) were anti-dsDNA positive and 224 (69.8%) had low complement levels. At baseline, the mean SLEDAI-2K score was 10.4 (±5.25); 152 (47.5%) of patients had damage with a mean SDI score of 0.83 (±1.2). A total of 289 patients (89.2%) had received disease modifying anti-rheumatic drugs (DMARDs) before BLM: conventional (cDMARDS) in 282 patients (87%) and biologic DMARDs (bDMARDs) in 74 patients (22.8%); 164 (51.9%) had received more than one cDMARDs, methotrexate being the most frequently used (44.4%). Other cDMARDs used were: mycophenolate mofetil in 104 (37.01%), azathioprine in 91 (32.38%), leflunomide in 29 (10.32%), cyclophosphamide in 28 (9.92%) and calcineurin inhibitors in 13 (4.6%) of patients. The most frequent bDMARDs used was Rituximab in 80%. Most patients were receiving antimalarials (83,2%) and glucocorticoids (GC) (91.2%), with a mean dose of 12.3 mg/day. A total of 209 (67.9%) patients were receiving more than 5 mg/day and 180 (58.4%) more than 7.5 mg/day of prednisone.BLM was used in monotherapy in 99 (30.5%) subjects. It was initiated due to disease activity in 307 patients (95%) and/or as a GC sparing agent in 191 patients (59%). Most patients initiated BLM for several concurrent reason; only a few patients received BLM just for maintenance (4/322) or save GC (8/322). At baseline, only 6 patients (1.9%) were in DORIS-21-remission and LLDAS. The main reasons of prescription for ongoing activity were arthritis (65.4%), cutaneous (40.7 %) or both (81%). There were no statistically significant differences in any of the prescription reasons when comparing the periods 2010-2015 and 2016-2021.Table 1.Type and reasons of prescription of BelimumabN (%) or mean (± SD) (n = 324 patients)Age at prescription of Belimumab (years)42.3 (± 12.9)Intravenous Belimumab215 (66.35%)Subcutaneous Belimumab110 (33%)Reasons of prescription* (multiple response allowed)Disease activity307 (95%)Maintenance197 (61%)Glucocorticoid sparing191 (59 %)ActivityCutaneous132 (40.7 %)Articular212 (65.4%)Renal58 (17,9%)Hematological60 (18.5%)Serosal47 (14.5%)Other29 (8.82%)ConclusionIn the majority of patients, belimumab was prescribed after the use of other DMARDs and more than 50% of patients had received at least 2 DMARDs and were receiving GC at medium doses. One third of patients received BLM as monotherapy. It was prescribed due to active disease in the vast majority of patients and/or as GC sparing agent. Activity in articular and cutaneous domains were the main reasons of indication. No changes in prescription habits were identified over time.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
Reporter genes (e.g. beta-galactosidase, chloramphenicol-acetyltransferase, green fluorescent protein, luciferase) play critical roles in investigating mechanisms of gene expression in transgenic ...animals and in developing gene delivery systems for gene therapy. However, measuring expression of these reporter genes requires biopsy or death. We now report a procedure to image reporter gene expression repetitively and non-invasively in living animals with positron emission tomography (PET), using the dopamine type 2 receptor (D2R) as a reporter gene and 3-(2'-18Ffluoroethyl)spiperone (FESP) as a reporter probe. We use a viral delivery system to demonstrate the ability of this PET reporter gene/PET reporter probe system to image reporter gene expression following somatic gene transfer. In mice injected intravenously with replication-deficient adenovirus carrying a D2R reporter gene, PET in vivo measures of hepatic 18F retention are proportional to in vitro measures of hepatic FESP retention, D2R ligand binding and D2R mRNA. We use tumor-forming cells carrying a stably transfected D2R gene to demonstrate imaging of this PET reporter gene/PET reporter probe system in 'tissues'. Tumors expressing the transfected D2R reporter gene retain substantially more FESP than control tumors. The D2R/FESP reporter gene/reporter probe system should be a valuable technique to monitor, in vivo, expression from both gene therapy vectors and transgenes.
We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting ...8-18Ffluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression$(r^{2}>0.80)$. Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.
MAGIC detection of GRB 201216C at z = 1.1 Acciari, V A; Agudo, I; Aniello, T ...
Monthly notices of the Royal Astronomical Society,
01/2024, Volume:
527, Issue:
3
Journal Article
Peer reviewed
Open access
ABSTRACT
Gamma-ray bursts (GRBs) are explosive transient events occurring at cosmological distances, releasing a large amount of energy as electromagnetic radiation over several energy bands. We ...report the detection of the long GRB 201216C by the MAGIC telescopes. The source is located at z = 1.1 and thus it is the farthest one detected at very high energies. The emission above 70 GeV of GRB 201216C is modelled together with multiwavelength data within a synchrotron and synchrotron self-Compton (SSC) scenario. We find that SSC can explain the broad-band data well from the optical to the very-high-energy band. For the late-time radio data, a different component is needed to account for the observed emission. Differently from previous GRBs detected in the very-high-energy range, the model for GRB 201216C strongly favours a wind-like medium. The model parameters have values similar to those found in past studies of the afterglows of GRBs detected up to GeV energies.
PDF
