De novo head and neck cancer after liver transplant with antibody-based immunosuppression induction

Background Powerful antibody-based immunosuppression induction is now used routinely during organ transplantation, and may place patients at even higher risk of post-transplant cancer. Materials and Methods Incidence of de-novo head and neck cancer was extracted from the records of 1685 consecutive adult, deceased donor liver transplant recipients with a minimum 1-year follow-up from 2001 to 2015. There were 121 patients positively identified as having developed de-novo head and neck cancer post-liver transplant. Records of these patients were analyzed to determine demographics, history of cancer pre-liver transplant, de-novo cancer type and location, treatment modalities, and alcohol and tobacco exposure. Results Of the 121 patients who developed cancer of the head and neck (7%), there were 103 cutaneous (6%) and 25 non-cutaneous (1%). For non-cutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (p<0.001), any smoking history (p=0.05), and increasing exposure to tobacco (p<0.01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop non-cutaneous cancer (p=0.06), but a survival advantage for patients who develop cutaneous cancer (p<0.01). Conclusions The incidence and pattern of head and neck cancer in this population of liver transplant patients was similar to those published previously, suggesting that induction immunosuppression does not increase risk of these types of cancers. Long term survival was worse for patients with non-cutaneous cancers, but better for those with cutaneous cancers, though the reason is unclear

Connecting the time domain community with the Virtual Astronomical Observatory

The time domain has been identified as one of the most important areas of astronomical research for the next decade. The Virtual Observatory is in the vanguard with dedicated tools and services that enable and facilitate the discovery, dissemination and analysis of time domain data. These range in scope from rapid notifications of time-critical astronomical transients to annotating long-term variables with the latest modeling results. In this paper, we will review the prior art in these areas and focus on the capabilities that the VAO is bringing to bear in support of time domain science. In particular, we will focus on the issues involved with the heterogeneous collections of (ancillary) data associated with astronomical transients, and the time series characterization and classification tools required by the next generation of sky surveys, such as LSST and SKA.Comment: Submitted to Proceedings of SPIE Observatory Operations: Strategies, Processes and Systems IV, Amsterdam, 2012 July 2-

Constraining the Progenitor Companion of the Nearby Type Ia SN 2011fe with a Nebular Spectrum at +981 Days

We present an optical nebular spectrum of the nearby Type Ia supernova 2011fe, obtained 981 days after explosion. SN 2011fe exhibits little evolution since the +593 day optical spectrum, but there are several curious aspects in this new extremely late-time regime. We suggest that the persistence of the $\sim5800$~\AA\ feature is due to Na I D, and that a new emission feature at $\sim7300$~\AA\ may be [Ca II]. Also, we discuss whether the new emission feature at $\sim6400$~\AA\ might be [Fe I] or the high-velocity hydrogen predicted by Mazzali et al. The nebular feature at 5200~\AA\ exhibits a linear velocity evolution of $\sim350$ $\rm km\ s^{-1}$ per 100 days from at least +220 to +980 days, but the line's shape also changes in this time, suggesting that line blending contributes to the evolution. At $\sim 1000$ days after explosion, flux from the SN has declined to a point where contribution from a luminous secondary could be detected. In this work we make the first observational tests for a post-impact remnant star and constrain its temperature and luminosity to $T \gtrsim 10^4$ $\rm K$ and $L \lesssim 10^4$ $\rm L_{\odot}$. Additionally, we do not see any evidence for narrow H$\alpha$ emission in our spectrum. We conclude that observations continue to strongly exclude many single-degenerate scenarios for SN 2011fe.Comment: 11 pages, 10 figures, published by MNRA

Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting

Background: An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. Methods: Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. Results: The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P 3.36). Conclusion: An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.Peer reviewedAuthor versio

Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

Prospects of Detecting Non-thermal Protons in Solar Flares via Lyman Line Spectroscopy: Revisiting the Orrall-Zirker Effect

Solar flares are efficient particle accelerators, with a substantial fraction of the energy released manifesting as non-thermal particles. While the role that non-thermal electrons play in transporting flare energy is well studied, the properties and importance of non-thermal protons is rather less well understood. This is in large part due to the paucity of diagnostics, particularly at the lower-energy (deka-keV) range of non-thermal proton distributions in flares. One means to identify the presence of deka-keV protons is by an effect originally described by \cite{1976ApJ...208..618O}. In the Orrall-Zirker effect, non-thermal protons interact with ambient neutral hydrogen, and via charge exchange produce a population of energetic neutral atoms (ENAs) in the chromosphere. These ENAs subsequently produce an extremely redshifted photon in the red wings of hydrogen spectral lines. We revisit predictions of the strength of this effect using modern interaction cross-sections, and numerical models capable of self-consistently simulating the flaring non-equilibrium ionization stratification, and the non-thermal proton distribution (and, crucially, their feedback on each other). We synthesize both the thermal and non-thermal emission from \lya\ and \lyb, the most promising lines that may exhibit a detectable signal. These new predictions are are weaker and more transient than prior estimates, but the effects should be detectable in fortuitous circumstances. We degrade the \lyb\ emission to the resolution of the Spectral Imaging of the Coronal Environment (SPICE) instrument on board Solar Orbiter, demonstrating that though likely difficult, it should be possible to detect the presence of non-thermal protons in flares observed by SPICE.Comment: Accepted for publication in The Astrophysical Journa

Sorting live stem cells based on Sox2 mRNA expression.

PMCID: PMC3507951This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs) offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES) and neural stem cells (NSC). One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+)SSEA1(+) cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+) cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(-) cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner

Laser Sounder Approach for Global Measurement of Tropospheric CO2 Mixing Ratio from Space

We report progress in assessing the feasibility of a new satellite-based laser-sounding instrument to measure CO2 and other trace gas abundances in the lower troposphere from space

The Very Young Type Ia Supernova 2012cg: Discovery and Early-Time Follow-Up Observations

On 2012 May 17.2 UT, only 1.5 +/- 0.2 d after explosion, we discovered SN 2012cg, a Type Ia supernova (SN Ia) in NGC 4424 (d ~ 15 Mpc). As a result of the newly modified strategy employed by the Lick Observatory SN Search, a sequence of filtered images was obtained starting 161 s after discovery. Utilizing recent models describing the interaction of SN ejecta with a companion star, we rule out a ~1 M_Sun companion for half of all viewing angles and a red-giant companion for nearly all orientations. SN 2012cg reached a B-band maximum of 12.09 +/- 0.02 mag on 2012 June 2.0 and took ~17.3 d from explosion to reach this, typical for SNe Ia. Our pre-maximum brightness photometry shows a narrower-than-average B-band light curve for SN 2012cg, though slightly overluminous at maximum brightness and with normal color evolution (including some of the earliest SN Ia filtered photometry ever obtained). Spectral fits to SN 2012cg reveal ions typically found in SNe Ia at early times, with expansion velocities >14,000 km/s at 2.5 d past explosion. Absorption from C II is detected early, as well as high-velocity components of both Si II 6355 Ang. and Ca II. Our last spectrum (13.5 d past explosion) resembles that of the somewhat peculiar SN Ia 1999aa. This suggests that SN 2012cg will have a slower-than-average declining light curve, which may be surprising given the faster-than-average rising light curve.Comment: re-submitted to ApJL, 4 figures, 1 tabl