Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, may lower treatment side effects without compromising tumor control. This is achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the healthy tissue. Optimization of such treatments is based on biologically effective dose (BED), which leads to computationally challenging nonconvex optimization problems. Current optimization methods yield only locally optimal plans, and it has been unclear whether these are close to the global optimum. We present an optimization model to compute rigorous bounds on the normal tissue BED reduction achievable by such plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising other treatment objectives. First a uniformly fractionated reference plan is computed using convex optimization. Then a nonconvex quadratically constrained quadratic programming model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a lower bound on the lowest achievable mean liver BED. The method is presented on 5 cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the reference plans, which corresponds to 79-97% of the gap between the reference mean liver BEDs and our lower bounds. This indicates that spatiotemporal treatments can achieve substantial reduction in normal tissue BED, and that local optimization provides plans that are close to realizing the maximum potential benefit

High-pressure, low-abundance water in bipolar outflows. Results from a Herschel-WISH survey

(Abridged) We present a survey of the water emission in a sample of more than 20 outflows from low mass young stellar objects with the goal of characterizing the physical and chemical conditions of the emitting gas. We have used the HIFI and PACS instruments on board the Herschel Space Observatory to observe the two fundamental lines of ortho-water at 557 and 1670 GHz. These observations were part of the "Water In Star-forming regions with Herschel" (WISH) key program, and have been complemented with CO and H2 data. We find that the emission from water has a different spatial and velocity distribution from that of the J=1-0 and 2-1 transitions of CO, but it has a similar spatial distribution to H2, and its intensity follows the H2 intensity derived from IRAC images. This suggests that water traces the outflow gas at hundreds of kelvins responsible for the H2 emission, and not the component at tens of kelvins typical of low-J CO emission. A warm origin of the water emission is confirmed by a remarkable correlation between the intensities of the 557 and 1670 GHz lines, which also indicates the emitting gas has a narrow range of excitations. A non-LTE radiative transfer analysis shows that while there is some ambiguity on the exact combination of density and temperature values, the gas thermal pressure nT is constrained within less than a factor of 2. The typical nT over the sample is 4 10^{9} cm^{-3}K, which represents an increase of 10^4 with respect to the ambient value. The data also constrain within a factor of 2 the water column density. When this quantity is combined with H2 column densities, the typical water abundance is only 3 10^{-7}, with an uncertainty of a factor of 3. Our data challenge current C-shock models of water production due to a combination of wing-line profiles, high gas compressions, and low abundances.Comment: 21 pages, 13 figures. Accepted for publication in A&

Water in low-mass star-forming regions with Herschel (WISH-LM): High-velocity H2O bullets in L1448-MM observed with HIFI

Herschel-HIFI observations of water in the low-mass star-forming object L1448-MM, known for its prominent outflow, are presented, as obtained within the `Water in star-forming regions with Herschel' (WISH) key programme. Six H2-16O lines are targeted and detected (E_up/k_B ~ 50-250 K), as is CO J= 10-9 (E_up/k_B ~ 305 K), and tentatively H2-18O 110-101 at 548 GHz. All lines show strong emission in the "bullets" at |v| > 50 km/s from the source velocity, in addition to a broad, central component and narrow absorption. The bullets are seen much more prominently in H$_2$O than in CO with respect to the central component, and show little variation with excitation in H2O profile shape. Excitation conditions in the bullets derived from CO lines imply a temperature >150 K and density >10^5 cm^-3, similar to that of the broad component. The H2O/CO abundance ratio is similar in the "bullets" and the broad component, ~ 0.05-1.0, in spite of their different origins in the molecular jet and the interaction between the outflow and the envelope. The high H2O abundance indicates that the bullets are H2 rich. The H2O cooling in the "bullets" and the broad component is similar and higher than the CO cooling in the same components. These data illustrate the power of Herschel-HIFI to disentangle different dynamical components in low-mass star-forming objects and determine their excitation and chemical conditions.Comment: Accepted for publication in A&

APEX-CHAMP+ high-J CO observations of low-mass young stellar objects: III. NGC 1333 IRAS 4A/4B envelope, outflow and UV heating

NGC 1333 IRAS 4A and IRAS 4B sources are among the best studied Stage 0 low-mass protostars which are driving prominent bipolar outflows. Most studies have so far concentrated on the colder parts (T<30K) of these regions. The aim is to characterize the warmer parts of the protostellar envelope in order to quantify the feedback of the protostars on their surroundings in terms of shocks, UV heating, photodissociation and outflow dispersal. Fully sampled large scale maps of the region were obtained; APEX-CHAMP+ was used for 12CO 6-5, 13CO 6-5 and [CI] 2-1, and JCMT-HARP-B for 12CO 3-2 emissions. Complementary Herschel-HIFI and ground-based lines of CO and its isotopologs, from 1-0 upto 10-9 (Eu/k 300K), are collected at the source positions. Radiative-transfer models of the dust and lines are used to determine temperatures and masses of the outflowing and UV-heated gas and infer the CO abundance structure. Broad CO emission line profiles trace entrained shocked gas along the outflow walls, with typical temperatures of ~100K. At other positions surrounding the outflow and the protostar, the 6-5 line profiles are narrow indicating UV excitation. The narrow 13CO 6-5 data directly reveal the UV heated gas distribution for the first time. The amount of UV-heated and outflowing gas are found to be comparable from the 12CO and 13CO 6-5 maps, implying that UV photons can affect the gas as much as the outflows. Weak [CI] emission throughout the region indicates a lack of CO dissociating photons. Modeling of the C18O lines indicates the necessity of a "drop" abundance profile throughout the envelope where the CO freezes out and is reloaded back into the gas phase, thus providing quantitative evidence for the CO ice evaporation zone around the protostars. The inner abundances are less than the canonical value of CO/H_2=2.7x10^-4, indicating some processing of CO into other species on the grains.Comment: 20 pages, 22 figures, Accepted by A&

APEX-CHAMP+ high-J CO observations of low-mass young stellar objects: IV. Mechanical and radiative feedback

During the embedded stage of star formation, bipolar molecular outflows and UV radiation from the protostar are important feedback processes. Our aim is to quantify the feedback, mechanical and radiative, for a large sample of low-mass sources. The outflow activity is compared to radiative feedback in the form of UV heating by the accreting protostar to search for correlations and evolutionary trends. Large-scale maps of 26 young stellar objects, which are part of the Herschel WISH key program are obtained using the CHAMP+ instrument on the APEX (12CO and 13CO 6-5), and the HARP-B instrument on the JCMT (12CO and 13CO 3-2). Maps are used to determine outflow parameters and envelope models are used to quantify the amount of UV-heated gas and its temperature from 13CO 6-5 observations. All sources in our sample show outflow activity and the outflow force, F_CO, is larger for Class 0 sources than for Class I sources, even if their luminosities are comparable. The outflowing gas typically extends to much greater distances than the power-law envelope and therefore influences the surrounding cloud material directly. Comparison of the CO 6-5 results with Herschel-HIFI H2O and PACS high-J CO lines, both tracing currently shocked gas, shows that the two components are linked, even though the transitions do not probe the same gas. The link does not extend down to CO 3-2. The conclusion is that CO 6-5 depends on the shock characteristics (density and velocity), whereas CO 3-2 is more sensitive to conditions in the surrounding environment (density). The radiative feedback is responsible for increasing the gas temperature by a factor of two, up to 30-50 K, on scales of a few thousand AU, particularly along the direction of the outflow. The mass of the UV heated gas exceeds the mass contained in the entrained outflow in the inner ~3000 AU and is therefore at least as important on small scales.Comment: 30 pages with Appendix, Accepted by Astronomy & Astrophysic

The abundance of C18O and HDO in the envelope and hot core of the intermediate mass protostar NGC 7129 FIRS 2

NGC 7129 FIRS 2 is a young intermediate-mass (IM) protostar, which is associated with two energetic bipolar outflows and displays clear signs of the presence of a hot core. It has been extensively observed with ground based telescopes and within the WISH Guaranteed Time Herschel Key Program. We present new observations of the C18O 3-2 and the HDO 3_{12}-2_{21} lines towards NGC 7129 FIRS 2. Combining these observations with Herschel data and modeling their emissions, we constrain the C18O and HDO abundance profiles across the protostellar envelope. In particular, we derive the abundance of C18O and HDO in the hot core. The intensities of the C18O lines are well reproduced assuming that the C18O abundance decreases through the protostellar envelope from the outer edge towards the centre until the point where the gas and dust reach the CO evaporation temperature (~20-25 K) where the C18O is released back to the gas phase. Once the C18O is released to the gas phase, the modelled C18O abundance is found to be ~1.6x10^{-8}, which is a factor of 10 lower than the reference abundance. This result is supported by the non-detection of C18O 9-8, which proves that even in the hot core (T_k>100 K) the CO abundance must be 10 times lower than the reference value. Several scenarios are discussed to explain this C18O deficiency. One possible explanation is that during the pre-stellar and protostellar phase, the CO is removed from the grain mantles by reactions to form more complex molecules. Our HDO modeling shows that the emission of HDO 3_{12}-2_{21} line is maser and comes from the hot core (T_k>100 K). Assuming the physical structure derived by Crimier et al. (2010), we determine a HDO abundance of ~0.4 - 1x10^{-7} in the hot core of this IM protostar, similar to that found in the hot corinos NGC 1333 IRAS 2A and IRAS 16293-2422.Comment: 10 pages, 7 figure

High-J CO emission in the Cepheus E protostellar outflow observed with SOFIA/GREAT

We present and analyze two spectrally resolved high-J CO lines towards the molecular outflow Cep E, driven by an intermediate-mass class 0 protostar. Using the GREAT receiver on board SOFIA, we observed the CO (12--11) and (13--12) transitions (E_u ~ 430 and 500 K, respectively) towards one position in the blue lobe of this outflow, that had been known to display high-velocity molecular emission. We detect the outflow emission in both transitions, up to extremely high velocities (~ 100 km/s with respect to the systemic velocity). We divide the line profiles into three velocity ranges that each have interesting spectral features: standard, intermediate, and extremely high-velocity. One distinct bullet is detected in each of the last two. A large velocity gradient analysis for these three velocity ranges provides constraints on the kinetic temperature and volume density of the emitting gas, >~ 100 K and > ~ 10^4 cm^-3, respectively. These results are in agreement with previous ISO observations and are comparable with results obtained by Herschel for similar objects. We conclude that high-J CO lines are a good tracer of molecular bullets in protostellar outflows. Our analysis suggests that different physical conditions are at work in the intermediate velocity range compared with the standard and extremely high-velocity gas at the observed position.Comment: Accepted for publication in A&A (SOFIA/GREAT special issue

Properties of 42 Solar-type Kepler Targets from the Asteroseismic Modeling Portal

Recently the number of main-sequence and subgiant stars exhibiting solar-like oscillations that are resolved into individual mode frequencies has increased dramatically. While only a few such data sets were available for detailed modeling just a decade ago, the Kepler mission has produced suitable observations for hundreds of new targets. This rapid expansion in observational capacity has been accompanied by a shift in analysis and modeling strategies to yield uniform sets of derived stellar properties more quickly and easily. We use previously published asteroseismic and spectroscopic data sets to provide a uniform analysis of 42 solar-type Kepler targets from the Asteroseismic Modeling Portal (AMP). We find that fitting the individual frequencies typically doubles the precision of the asteroseismic radius, mass and age compared to grid-based modeling of the global oscillation properties, and improves the precision of the radius and mass by about a factor of three over empirical scaling relations. We demonstrate the utility of the derived properties with several applications.Comment: 12 emulateapj pages, 9 figures, 1 online-only extended figure, 1 table, ApJS accepted (typo corrected in Eq.8

The prognostic impact of comorbidity, nutritional and performance status on patients with diffuse large B cell lymphoma

Background: The aim of the study was to investigate the impact of nutritional status, comorbidity, and performance status on patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective study was conducted on 112 DLBCL patients who were diagnosed at our center between 2009 and 2018. Demographic and disease characteristics and laboratory test results were recorded. Assessments were made using the age-adjusted Charlson comorbidity index (CCI-A) for comorbidity, albumin level for nutritional status, and Eastern Cooperative Oncology Group (ECOG) score for performance status. Results: The mean age of the patients was found to be 62.63 ± 15.16 years. The ECOG score of 65 patients (69.1%) was in the range of 0-1. The mean follow-up time of the patients was determined to be 25.24 ± 25.11 months, and at the end of the follow-up period, 64 patients (57.1%) were survivors. The progression-free survival (PFS), overall survival (OS), and 5-year OS rates of those with CCI-A > 4 were found to be significantly lower than those with CCI-A score ≤4 (P < 0.05). As a result of the Cox-Regression (Backward: LR method) analysis, ECOG and albumin levels were found to be independent risk factors for both OS and PFS (P < 0.05). Conclusion: This study demonstrated that CCI-A, ECOG, and nutritional status are independent prognostic markers for DLBCL patients. Initial evaluation of these patients should include all these parameters, which are easily available at the time of diagnosis