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    Chandra Reveals Variable Multi-Component X-ray Emission from FU Orionis

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    FU Orionis is the prototype of a class of eruptive young stars (``FUors'') characterized by strong optical outbursts. We recently completed an exploratory survey of FUors using XMM-Newton to determine their X-ray properties, about which little was previously known. The prototype FU Ori and V1735 Cyg were detected. The X-ray spectrum of FU Ori was found to be unusual, consisting of a cool moderately-absorbed component plus a hotter component viewed through an absorption column density that is an order of magnitude higher. We present here a sensitive (99 ks) follow-up X-ray observation of FU Ori obtained at higher angular resolution with Chandra ACIS-S. The unusual multi-component spectrum is confirmed. The hot component is centered on FU Ori and dominates the emission above 2 keV. It is variable (a signature of magnetic activity) and is probably coronal emission originating close to FU Ori's surface viewed through cool gas in FU Ori's strong wind or accretion stream. In contrast, the X-ray centroid of the soft emission below 2 keV is offset 0.20 arcsec to the southeast of FU Ori, toward the near-IR companion (FU Ori S). This offset amounts to slightly less than half the separation between the two stars. The most likely explanation for the offset is that the companion contributes significantly to the softer X-ray emission below 2 keV (and weakly above 2 keV). The superimposed X-ray contributions from FU Ori and the companion resolve the paradox posed by XMM-Newton of an apparently single X-ray source viewed through two different absorption columns.Comment: 21 pages, 3 tables, 6 figure

    Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

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    Objective Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50–60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. Methods High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Results Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Conclusion Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population

    Constraining mass ratio and extinction in the FU Orionis binary system with infrared integral field spectroscopy

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    We report low resolution near infrared spectroscopic observations of the eruptive star FU Orionis using the Integral Field Spectrograph Project 1640 installed at the Palomar Hale telescope. This work focuses on elucidating the nature of the faint source, located 0.5" south of FU Ori, and identified in 2003 as FU Ori S. We first use our observations in conjunction with published data to demonstrate that the two stars are indeed physically associated and form a true binary pair. We then proceed to extract J and H band spectro-photometry using the damped LOCI algorithm, a reduction method tailored for high contrast science with IFS. This is the first communication reporting the high accuracy of this technique, pioneered by the Project 1640 team, on a faint astronomical source. We use our low resolution near infrared spectrum in conjunction with 10.2 micron interferometric data to constrain the infrared excess of FU Ori S. We then focus on estimating the bulk physical properties of FU Ori S. Our models lead to estimates of an object heavily reddened, A_V =8-12, with an effective temperature of ~ 4000-6500 K . Finally we put these results in the context of the FU Ori N-S system and argue that our analysis provides evidence that FU Ori S might be the more massive component of this binary syste

    The enigmatic young brown dwarf binary FU Tau: accretion and activity

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    FU Tau belongs to a rare class of young, wide brown dwarf binaries. We have resolved the system in a Chandra X-ray observation and detected only the primary, FU Tau A. Hard X-ray emission, presumably from a corona, is present but, unexpectedly, we detect also a strong and unusually soft component from FU Tau A. Its X-ray properties, so far unique among brown dwarfs, are very similar to those of the T Tauri star TW Hya. The analogy with TW Hya suggests that the dominating soft X-ray component can be explained by emission from accretion shocks. However, the typical free-fall velocities of a brown dwarf are too low for an interpretation of the observed X-ray temperature as post-shock region. On the other hand, velocities in excess of the free-fall speed are derived from archival optical spectroscopy, and independent pieces of evidence for strong accretion in FU Tau A are found in optical photometry. The high X-ray luminosity of FU Tau A coincides with a high bolometric luminosity confirming an unexplained trend among young brown dwarfs. In fact, FU Tau A is overluminous with respect to evolutionary models while FU Tau B is on the 1 Myr isochrone suggesting non-contemporaneous formation of the two components in the binary. The extreme youth of FU Tau A could be responsible for its peculiar X-ray properties, in terms of atypical magnetic activity or accretion. Alternatively, rotation and magnetic field effects may reduce the efficiency of convection which in turn affects the effective temperature and radius of FU Tau A shifting its position in the HR diagram. Although there is no direct prove of this latter scenario so far we present arguments for its plausibility.Comment: Accepted for publication in MNRAS; 9 pages, 5 figure

    Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

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    Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

    EuroEco (European Health Economic Trial on Home Monitoring in ICD Patients): a provider perspective in five European countries on costs and net financial impact of follow-up with or without remote monitoring

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    Aim: Remote follow-up (FU) of implantable cardiac defibrillators (ICDs) allows for fewer in-office visits in combination with earlier detection of relevant findings. Its implementation requires investment and reorganization of care. Providers (physicians or hospitals) are unsure about the financial impact. The primary end-point of this randomized prospective multicentre health economic trial was the total FU-related cost for providers, comparing Home Monitoring facilitated FU (HM ON) to regular in-office FU (HM OFF) during the first 2 years after ICD implantation. Also the net financial impact on providers (taking national reimbursement into account) and costs from a healthcare payer perspective were evaluated. Methods and results: Atotal of 312 patients with VVI-or DDD-ICD implants from 17 centres in six EU countries were randomised to HMON or OFF, of which 303 were eligible for data analysis. For all contacts (in-office, calendar-or alert-triggered web-based review, discussions, calls) time-expenditure was tracked. Country-specific cost parameters were used to convert resource use into monetary values. Remote FU equipment itself was not included in the cost calculations. Given only two patients from Finland (one in each group) a monetary valuation analysis was not performed for Finland. Average age was 62.4 +/- 13.1 years, 81% were male, 39% received a DDD system, and 51% had a prophylactic ICD. Resource use with HM ON was clearly different: less FU visits (3.79 +/- 1.67 vs. 5.53 +/- 2.32; P < 0.001) despite a small increase of unscheduled visits (0.95 +/- 1.50 vs. 0.62 +/- 1.25; P < 0.005), more non-office-based contacts (1.95+3.29 vs. 1.01 +/- 2.64; P < 0.001), more Internet sessions (11.02 +/- 15.28 vs. 0.06 +/- 0.31; P < 0.001) and more in-clinic discussions (1.84 +/- 4.20 vs. 1.28 +/- 2.92; P < 0.03), but with numerically fewer hospitalizations (0.67 +/- 1.18 vs. 0.85 +/- 1.43, P = 0.23) and shorter length-of-stay (6.31 +/- 15.5 vs. 8.26 +/- 18.6; P = 0.27), although not significant. For the whole study population, the total FU cost for providers was not different for HM ON vs. OFF [mean (95% CI): (sic)204 169-238) vs. (sic)213 (182-243); range for difference ((sic)-36 to 54), NS]. From a payer perspective, FU-related costs were similar while the total cost per patient (including other physician visits, examinations, and hospitalizations) was numerically (but not significantly) lower. There was no difference in the net financial impact on providers [profit of (sic)408 (327-489) vs. (sic)400 (345-455); range for difference ((sic)-104 to 88), NS], but there was heterogeneity among countries, with less profit for providers in the absence of specific remote FU reimbursement (Belgium, Spain, and the Netherlands) and maintained or increased profit in cases where such reimbursement exists (Germany and UK). Quality of life (SF-36) was not different. Conclusion: For all the patients as a whole, FU-related costs for providers are not different for remote FU vs. purely in-office FU, despite reorganized care. However, disparity in the impact on provider budget among different countries illustrates the need for proper reimbursement to ensure effective remote FU implementation

    Diagnosing 0.1–10 au Scale Morphology of the FU Ori Disk Using ALMA and VLTI/GRAVITY

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    We report new Atacama Large Millimeter/submillimeter Array Band 3 (86–100 GHz; ~80 mas angular resolution) and Band 4 (146–160 GHz; ~50 mas angular resolution) observations of the dust continuum emission toward the archetypal and ongoing accretion burst young stellar object FU Ori, which simultaneously covered its companion, FU Ori S. In addition, we present near-infrared (2–2.45 μm) observations of FU Ori taken with the General Relativity Analysis via VLT InTerferometrY (GRAVITY; ~1 mas angular resolution) instrument on the Very Large Telescope Interferometer (VLTI). We find that the emission in both FU Ori and FU Ori S at (sub)millimeter and near-infrared bands is dominated by structures inward of ~10 au radii. We detected closure phases close to zero from FU Ori with VLTI/GRAVITY, which indicate the source is approximately centrally symmetric and therefore is likely viewed nearly face-on. Our simple model to fit the GRAVITY data shows that the inner 0.4 au radii of the FU Ori disk has a triangular spectral shape at 2–2.45 μm, which is consistent with the H2O and CO absorption features in a 10−4 M ⊙ yr−1, viscously heated accretion disk. At larger (~0.4–10 au) radii, our analysis shows that viscous heating may also explain the observed (sub)millimeter and centimeter spectral energy distribution when we assume a constant, ~10−4 M ⊙ yr−1 mass inflow rate in this region. This explains how the inner 0.4 au disk is replenished with mass at a modest rate, such that it neither depletes nor accumulates significant masses over its short dynamic timescale. Finally, we tentatively detect evidence of vertical dust settling in the inner 10 au of the FU Ori disk, but confirmation requires more complete spectral sampling in the centimeter bands
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