Planet Hunters IX. KIC 8462852 – where's the flux? Boyajian, T. S.; LaCourse, D. M.; Rappaport, S. A. ...
Monthly Notices of the Royal Astronomical Society,
04/2016, Letnik:
457, Številka:
4
Journal Article
A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy.
We carried out a retrospective analysis of prospectively collected data from ...consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population.
One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268 and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed.
The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.
•Recent evidences suggest that non-viral HCCs could be less responsive to immunotherapy.•Lenvatinib performs better compared to atezolizumab plus bevacizumab in non-viral HCC.•Sorafenib performs similarly to atezolizumab plus bevacizumab in non-viral HCC.
Planet Hunters IX. KIC 8462852 – where's the flux? Boyajian, T. S; LaCourse, D. M; Rappaport, S. A ...
Monthly notices of the Royal Astronomical Society,
04/2016, Letnik:
457, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Over the duration of the Kepler mission, KIC 8462852 was observed to undergo irregularly shaped, aperiodic dips in flux of up to ∼20 per cent. The dipping activity can last for between 5 and 80 d. We ...characterize the object with high-resolution spectroscopy, spectral energy distribution fitting, radial velocity measurements, high-resolution imaging, and Fourier analyses of the Kepler light curve. We determine that KIC 8462852 is a typical main-sequence F3 V star that exhibits no significant IR excess, and has no very close interacting companions. In this paper, we describe various scenarios to explain the dipping events observed in the Kepler light curve. We confirm that the dipping signals in the data are not caused by any instrumental or data processing artefact, and thus are astrophysical in origin. We construct scenario-independent constraints on the size and location of a body in the system that are needed to reproduce the observations. We deliberate over several assorted stellar and circumstellar astrophysical scenarios, most of which have problems explaining the data in hand. By considering the observational constraints on dust clumps in orbit around a normal main-sequence star, we conclude that the scenario most consistent with the data in hand is the passage of a family of exocomet or planetesimal fragments, all of which are associated with a single previous break-up event, possibly caused by tidal disruption or thermal processing. The minimum total mass associated with these fragments likely exceeds 10−6 M⊕, corresponding to an original rocky body of >100 km in diameter. We discuss the necessity of future observations to help interpret the system.
Extracellular vesicles (EVs), including exosomes, are small membrane-bound particles released by cells. From a therapeutic point of view, EVs can often convey similar biological function as their ...parent cell. Grafts originating from oral mucosa have frequently been used in regenerative medicine, and we have previously described the use of oral cell sheets to prevent stricture formation of the esophagus. Further, we recently found that exosomes derived from these cell sheets have pro-regenerative effect on skin wound healing. Here, we have isolated exosomes from conditioned media from oral keratinocyte (“OKEx”) and dermal fibroblast (“FEx”) cultures. The exosomes were probed for classical EV-markers by western blot (CD9, annexin V and Flotillin-1), FEx were positive for all markers while OKEx were positive only for CD9. Tunable resistive pulse sensing indicated a mean size of around 110 nm and transmission electron microscopy showed a spherical morphology, for both groups. After fluorescent labelling, we studied the uptake of exosomes co-cultured with fibroblasts or keratinocytes. Signal from OKEx could be detected after 90 min, and signal could be detected in all groups after 16 h. Finally we studied the exosomes’ modulation of cell proliferation. Both groups suppressed proliferation of healthy keratinocyte and fibroblasts, at some doses to similar levels as dexamethasone (a drug commonly used to prevent stricture formation). In contrast, the exosomes also suppressed the proliferation of the carcinoma cell line TR146, while dexamethasone had no effect. In conclusion, we believe that exosome-signaling might be one of the mode-of-actions of cell sheet-therapy for stricture prevention.
•Oral keratinocyte exosomes can be isolated by size-exclusion chromotography.•The exosomes are positive for CD9, and are around 110 nm.•The exosomes are readily taken up by recipient cells.•The exosomes suppress proliferation of healthy and tumor cells.
Distal transradial approach (dTRA) for neuroendovascular procedures has received much attention in recent years as a newer and less invasive alternative to the conventional transfemoral or ...transradial approaches. We present the case of an 89-year-old woman with a basilar artery aneurysm requiring simultaneous catheterization of the bilateral vertebral arteries who was successfully embolized using bilateral dTRA. The aneurysm was accessed from the right vertebral artery using the right dTRA. Control angiograms during the procedure were performed from the left vertebral artery via the left dTRA. The operator's posture was ergonomically comfortable, and the catheters were easy to handle during the procedure. To the best of our knowledge, this is the first case of a bilateral dTRA used for neuroendovascular procedures. Bilateral dTRA is a safe and minimally invasive method for patients and ergonomically comfortable for operators.
PDF
