A lentiviral vector with a short troponin-I promoter for tracking cardiomyocyte differentiation of human embryonic stem cells

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Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation

Background: The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient’s inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation. Methods: Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume. Results: Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods. Conclusions: Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions

A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives

Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple–areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed

Gamma-ray flaring activity from the gravitationally lensed blazar PKS 1830-211 observed by Fermi LAT

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope routinely detects the highly dust-absorbed, reddened, and MeV-peaked flat spectrum radio quasar PKS 1830-211 (z=2.507). Its apparent isotropic gamma-ray luminosity (E>100 MeV) averaged over $\sim$ 3 years of observations and peaking on 2010 October 14/15 at 2.9 X 10^{50} erg s^{-1}, makes it among the brightest high-redshift Fermi blazars. No published model with a single lens can account for all of the observed characteristics of this complex system. Based on radio observations, one expects time delayed variability to follow about 25 days after a primary flare, with flux about a factor 1.5 less. Two large gamma-ray flares of PKS 1830-211 have been detected by the LAT in the considered period and no substantial evidence for such a delayed activity was found. This allows us to place a lower limit of about 6 on the gamma rays flux ratio between the two lensed images. Swift XRT observations from a dedicated Target of Opportunity program indicate a hard spectrum and with no significant correlation of X-ray flux with the gamma-ray variability. The spectral energy distribution can be modeled with inverse Compton scattering of thermal photons from the dusty torus. The implications of the LAT data in terms of variability, the lack of evident delayed flare events, and different radio and gamma-ray flux ratios are discussed. Microlensing effects, absorption, size and location of the emitting regions, the complex mass distribution of the system, an energy-dependent inner structure of the source, and flux suppression by the lens galaxy for one image path may be considered as hypotheses for understanding our results.Comment: 14 pages, 6 figures, 2 tables. Accepted by the The Astrophysical Journal. Corresponding authors: S. Ciprini (ASI ASDC & INAF OAR, Rome, Italy), S. Buson (INAF Padova & Univ. of Padova, Padova, Italy), J. Finke (NRL, Washington, DC, USA), F. D'Ammando (INAF IRA, Bologna, Italy

Search for extended gamma-ray emission from the Virgo galaxy cluster with Fermi-LAT

Galaxy clusters are one of the prime sites to search for dark matter (DM) annihilation signals. Depending on the substructure of the DM halo of a galaxy cluster and the cross sections for DM annihilation channels, these signals might be detectable by the latest generation of $\gamma$-ray telescopes. Here we use three years of Fermi Large Area Telescope (LAT) data, which are the most suitable for searching for very extended emission in the vicinity of nearby Virgo galaxy cluster. Our analysis reveals statistically significant extended emission which can be well characterized by a uniformly emitting disk profile with a radius of 3\deg that moreover is offset from the cluster center. We demonstrate that the significance of this extended emission strongly depends on the adopted interstellar emission model (IEM) and is most likely an artifact of our incomplete description of the IEM in this region. We also search for and find new point source candidates in the region. We then derive conservative upper limits on the velocity-averaged DM pair annihilation cross section from Virgo. We take into account the potential $\gamma$-ray flux enhancement due to DM sub-halos and its complex morphology as a merging cluster. For DM annihilating into $b\overline{b}$, assuming a conservative sub-halo model setup, we find limits that are between 1 and 1.5 orders of magnitude above the expectation from the thermal cross section for $m_{\mathrm{DM}}\lesssim100\,\mathrm{GeV}$. In a more optimistic scenario, we exclude $\langle \sigma v \rangle\sim3\times10^{-26}\,\mathrm{cm^{3}\,s^{-1}}$ for $m_{\mathrm{DM}}\lesssim40\,\mathrm{GeV}$ for the same channel. Finally, we derive upper limits on the $\gamma$-ray-flux produced by hadronic cosmic-ray interactions in the inter cluster medium. We find that the volume-averaged cosmic-ray-to-thermal pressure ratio is less than $\sim6\%$.Comment: 15 pages, 11 figures, 4 tables, accepted for publication in ApJ; corresponding authors: T. Jogler, S. Zimmer & A. Pinzk

Deep Broadband Observations of the Distant Gamma-ray Blazar PKS 1424+240

We present deep VERITAS observations of the blazar PKS 1424+240, along with contemporaneous Fermi Large Area Telescope, Swift X-ray Telescope and Swift UV Optical Telescope data between 2009 February 19 and 2013 June 8. This blazar resides at a redshift of $z\ge0.6035$, displaying a significantly attenuated gamma-ray flux above 100 GeV due to photon absorption via pair-production with the extragalactic background light. We present more than 100 hours of VERITAS observations from three years, a multiwavelength light curve and the contemporaneous spectral energy distributions. The source shows a higher flux of (2.1$\pm0.3$)$\times10^{-7}$ ph m$^{-2}$s$^{-1}$ above 120 GeV in 2009 and 2011 as compared to the flux measured in 2013, corresponding to (1.02$\pm0.08$)$\times10^{-7}$ ph m$^{-2}$s$^{-1}$ above 120 GeV. The measured differential very high energy (VHE; $E\ge100$ GeV) spectral indices are $\Gamma=$3.8$\pm$0.3, 4.3$\pm$0.6 and 4.5$\pm$0.2 in 2009, 2011 and 2013, respectively. No significant spectral change across the observation epochs is detected. We find no evidence for variability at gamma-ray opacities of greater than $\tau=2$, where it is postulated that any variability would be small and occur on longer than year timescales if hadronic cosmic-ray interactions with extragalactic photon fields provide a secondary VHE photon flux. The data cannot rule out such variability due to low statistics.Comment: ApJL accepted March 17, 201

Discovery of very high energy gamma rays from PKS 1424+240 and multiwavelength constraints on its redshift

We report the first detection of very-high-energy (VHE) gamma-ray emission above 140 GeV from PKS 1424+240, a BL Lac object with an unknown redshift. The photon spectrum above 140 GeV measured by VERITAS is well described by a power law with a photon index of 3.8 +- 0.5_stat +- 0.3_syst and a flux normalization at 200 GeV of (5.1 +- 0.9_stat +- 0.5_syst) x 10^{-11} TeV^-1 cm^-2 s^-1, where stat and syst denote the statistical and systematical uncertainty, respectively. The VHE flux is steady over the observation period between MJD 54881 and 55003 (2009 February 19 to June 21). Flux variability is also not observed in contemporaneous high energy observations with the Fermi Large Area Telescope (LAT). Contemporaneous X-ray and optical data were also obtained from the Swift XRT and MDM observatory, respectively. The broadband spectral energy distribution (SED) is well described by a one-zone synchrotron self-Compton (SSC) model favoring a redshift of less than 0.1. Using the photon index measured with Fermi in combination with recent extragalactic background light (EBL) absorption models it can be concluded from the VERITAS data that the redshift of PKS 1424+240 is less than 0.66.Comment: accepted for publication, Ap

Constraints on dark matter models from a Fermi LAT search for high-energy cosmic-ray electrons from the Sun

During its first year of data taking, the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope has collected a large sample of high-energy cosmic-ray electrons and positrons (CREs). We present the results of a directional analysis of the CRE events, in which we searched for a flux excess correlated with the direction of the Sun. Two different and complementary analysis approaches were implemented, and neither yielded evidence of a significant CRE flux excess from the Sun. We derive upper limits on the CRE flux from the Sun's direction, and use these bounds to constrain two classes of dark matter models which predict a solar CRE flux: (1) models in which dark matter annihilates to CREs via a light intermediate state, and (2) inelastic dark matter models in which dark matter annihilates to CREs.Comment: 18 pages, 8 figures, accepted for publication in Physical Review D - contact authors: Francesco Loparco ([email protected]), M. Nicola Mazziotta ([email protected]) and Jennifer Siegal-Gaskins ([email protected]

Fermi observations of high-energy gamma-ray emission from GRB 090217A

The Fermi observatory is advancing our knowledge of Gamma-Ray Bursts (GRBs) through pioneering observations at high energies, covering more than 7 decades in energy with the two on-board detectors, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). Here we report on the observation of the long GRB 090217A which triggered the GBM and has been detected by the LAT with a significance greater than 9 sigma. We present the GBM and LAT observations and on-ground analyses, including the time-resolved spectra and the study of the temporal profile from 8 keV up to 1 GeV. All spectra are well reproduced by a Band model. We compare these observations to the first two LAT-detected, long bursts GRB 080825C and GRB 080916C. These bursts were found to have time-dependent spectra and exhibited a delayed onset of the high-energy emission, which are not observed in the case of GRB 090217A. We discuss some theoretical implications for the high-energy emission of GRBs.Comment: 17 pages, 4 figures. Contact Authors: Fred, Piron; Sara, Cutini; Andreas, von Kienli

Fermi observations of TeV-selected AGN

We report on observations of TeV-selected AGN made during the first 5.5 months of observations with the Large Area Telescope (LAT) on-board the Fermi Gamma-ray Space Telescope (Fermi). In total, 96 AGN were selected for study, each being either (i) a source detected at TeV energies (28 sources) or (ii) an object that has been studied with TeV instruments and for which an upper-limit has been reported (68 objects). The Fermi observations show clear detections of 38 of these TeV-selected objects, of which 21 are joint GeV-TeV sources and 29 were not in the third EGRET catalog. For each of the 38 Fermi-detected sources, spectra and light curves are presented. Most can be described with a power law of spectral index harder than 2.0, with a spectral break generally required to accommodate the TeV measurements. Based on an extrapolation of the Fermi spectrum, we identify sources, not previously detected at TeV energies, which are promising targets for TeV instruments. Evidence for systematic evolution of the $\gamma$-ray spectrum with redshift is presented and discussed in the context of interaction with the EBL.Comment: 51 pages, 6 figures, accepted for The Astronomical Journa