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Busulfan is given in the conditioning regimens preceding hematopoietic stem cell transplantation (HSCT), and plasma levels can be monitored. A targeted, individualized systemic exposure (SE) dose can be achieved by calculating the area under the plasma concentration versus time curve (AUC). The objective of this study was to determine a cutoff value for safety for the AUC for busulfan plasma levels in patients undergoing HSCT. A total of 149 consecutive HSCT patients were studied. After an oral test dose of busulfan, we set target doses of 4000, 5000, or 6000 µMol⸱min/day, and analyzed the AUC of oral or intravenous Bu. These patients were compared with 53 historical control subjects who had received myeloablative conditioning regimen without busulfan pharmacokinetic monitoring. Using a test dose and the administration route had no impact on the sinusoidal obstructive syndrome (SOS) incidence, transplant-related mortality or 1-year overall survival. However, patients receiving busulfan at doses set up at AUC > 5000 had an increased risk to develop SOS after HSCT (hazard ratio 3.39, p = 0.034, 95% CI 1.09-10.52). Adjusting the busulfan dose according to SE levels target dose during conditioning is associated with lower rates of oral severe mucositis and SOS. A cutoff of 5000 µMol⸱min is safe and does not impair survival.

We present H-band (1.65 $\mu$m) and SOFIA HAWC+ 154 $\mu$m polarization observations of the low-mass core L483. Our H-band observations reveal a magnetic field that is overwhelmingly in the E-W direction, which is approximately parallel to the bipolar outflow that is observed in scattered IR light and in single-dish $^{12}$CO observations. From our 154 $\mu$m data, we infer a $\sim$ 45$^{\circ}$ twist in the magnetic field within the inner 5" (1000 au) of L483. We compare these new observations with published single-dish 350 $\mu$m polarimetry and find that the 10,000 au scale H-band data match the smaller scale 350 $\mu$m data, indicating that the collapse of L483 is magnetically regulated on these larger scales. We also present high-resolution 1.3 mm ALMA data of L483 which reveals it is a close binary star with a separation of 34 au. The plane of the binary of L483 is observed to be approximately parallel to the twisted field in the inner 1000 au. Comparing this result to the $\sim$ 1000 au protostellar envelope, we find that the envelope is roughly perpendicular to the 1000 au HAWC+ field. Using the data presented, we speculate that L483 initially formed as a wide binary and the companion star migrated to its current position, causing an extreme shift in angular momentum thereby producing the twisted magnetic field morphology observed. More observations are needed to further test this scenario., Comment: Accepted for publication in ApJ

Despite a detailed understanding of the genes mutated in myelodysplastic syndromes (MDS), diagnostic and treatment decisions for patients with MDS rely primarily on clinical and cytogenetic variables as considered by the Revised International Prognostic Scoring System (IPSS-R). Here we describe the recently developed Molecular IPSS (IPSS-M), a clinico-genomic risk stratification system that considers clinical, cytogenetic and genetic parameters; the implementation of a web portal to facilitate its adoption, a strategy to handle missing variables, and the worldwide utilization of the web calculator as a clinical support tool. The IPSS-M was trained on 2,957 clinically annotated diagnostic MDS samples profiled for mutations in 156 driver genes. To maximize the clinical applicability of the IPSS-M and account for missing genetic data (i.e genes missing from a sequencing panel), we implemented a strategy to calculate a risk score under three scenarios: best, worst and average. Last, we developed an online calculator as a standalone single-page web application using VueJs, and D3Js for the interactive visualizations, deployed through a CI/CD pipeline on AWS, where collection of anonymous usage analytics allows to track adoption and usability of the new proposed model. The model incorporates clinical, morphological, genetic variables informed by cytogenetics and constructed from the presence of oncogenic mutations in 31 genes. It delivers a unique risk score for each individual patient, as well as an assignment to one of six IPSS-M risk strata. Compared to the IPSS-R the IPSS-M re-stratified 46% of MDS patients. The model was validated in an external dataset of 754 MDS patients. We released an open-access IPSS-M web calculator available at https://mds-risk-model.com. By specifying the patient clinical and molecular profiles, the tool returns the patient-specific IPSS-M risk score and category, and the probability estimates over time for three clinical endpoints, i.e. leukemia free survival (LFS), overall survival, and incidence of leukemic transformation. Since its launch in June 2022, the calculator has been used by >6000 users in >75 countries, reaching a daily average of 100 users per day. Risks have been calculated for >45,000 patient profiles. 99.28% of the sessions initiated reach an IPSS-M score, suggesting that the calculator is intuitive and easy to use. We trained and validated the IPSS-M on 3,711 patients, a patient tailored risk stratification tool for patients with MDS that considers clinical, morphological and genetic variables inclusive of cytogenetics and mutations in one of 31 genes. The development of a web based tool was instrumental to the global dissemination of the model, enabling non-expert users to leverage the power of molecular biomarkers in risk stratification for patients with MDS. Citation Format: Elsa Bernard, Juan E. Arango Ossa, Heinz Tuechler, Peter L. Greenberg, Robert P. Hasserjian, Yasuhito Nannya, Sean M. Devlin, Maria Creignou, Philippe Pinel, Lily Monier, Juan S. Medina-Martinez, Dylan Domenico, Martin Jädersten, Ulrich Germing, Guillermo Sanz, Arjan A. van de Loosdrecht, Olivier Kosmider, Matilde Y. Follo, Felicitas Thol, Lurdes Zamora, Ronald F. Pinheiro, Andrea Pellagatti, Detlef Haase, Pierre Fenaux, Monika Belickova, Michael R. Savona, Virginia M. Klimek, Fabio P. Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Solé, Uwe Platzbecker, Michael Heuser, Peter Valent, Kazuma Ohyashiki, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Michaela Fontenay, Joop H. Jansen, José Cervera, Norbert Gattermann, Benjamin L. Ebert, Rafael Bejar, Luca Malcovati, Mario Cazzola, Seishi Ogawa, Eva Hellström-Lindberg, Elli Papaemmanuil. Implementation and adoption of a web tool to support precision diagnostic and treatment decisions for patient with myelodysplastic syndromes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6168.

Myeloproliferative neoplasms (MPNs) constitute a group of hematologic clonal diseases that affect one or more myeloid lineages with an abnormal and abundant proliferation.16, 17 The World Health Organization (WHO) currently groups the MPNs into seven categories: Chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), polycythemia vera (PV), essential thrombocythemia (ET) primary myelofibrosis (PMF), chronic eosinophilic leukemia not otherwise specified (NOS) and, unclassifiable chronic myeloproliferative neoplasm (MPN-U). Mastocytosis is no longer included in that group.16 BCR-ABL1 fusion gene causes CML, identified by the translocation (9; 22) known as the Philadelphia chromosome (Ph), subject of prior guideline. Among the so-called Ph-negative MPNs, the most common ones include PV, ET, and PMF, herein the subject of this publication. PV, ET, and PMF share an anomaly in the JAK-STAT pathway, usually caused by genetic mutations on Janus kinase 2-JAK2 V617F, thrombopoietin receptor gene-myeloproliferative leukemia-MPL or calreticulin gene-CALR, which are mutually exclusive, and necessarily BCR-ABL negative (Table 1). PV, ET, and PMF share an anomaly in the JAK-STAT pathway, usually caused by mutations of the Janus kinase 2-JAK2 V617F genes, thrombopoietin receptor gene-myeloproliferative leukemia-MPL or calreticulin gene-CALR, that are mutually exclusive, and necessarily are BCR-ABL1 negative (Table 1). PV, ET, and PMF may arise alongside other mutations, as well as some cytogenetic abnormalities.16, 17 Despite the significant advances over recent years toward the characterization of genetic alterations, bone marrow morphological evaluation remains an important diagnosis tool.17 JAK2, MPL, and CALR mutations are not unique to these three conditions and may be present in other myeloid neoplasms, or even absent in some cases of PMF and ET.16 Table 1 Diagnostic criteria PV, ET, prefibrotic PMF and overt fibrotic PMF16(D).

[Context] Magnetic fields are predicted to play a significant role in the formation of filamentary structures and their fragmentation to form stars and star clusters., [Aims] We aim to investigate the role of the magnetic field in the process of core fragmentation toward the two hub–filament systems in the infrared dark cloud G14.225-0.506, which present different levels of fragmentation., [Methods] We performed observations of the thermal dust polarization at 350 μm using the Caltech Submillimeter Observatory (CSO) with an angular resolution of 10″ toward the two hubs (Hub-N and Hub-S) in the infrared dark cloud G14.225-0.506. We additionally applied the polarization–intensity-gradient method to estimate the significance of the magnetic field over the gravitational force., [Results] The sky-projected magnetic field in Hub-N shows a rather uniform structure along the east–west orientation, which is roughly perpendicular to the major axis of the hub–filament system. The intensity gradient in Hub-N displays a single local minimum coinciding with the dust core MM1a detected with interferometric observations. Such a prevailing magnetic field orientation is slightly perturbed when approaching the dust core. Unlike the northern Hub, Hub-S shows two local minima, reflecting the bimodal distribution of the magnetic field. In Hub-N, both east and west of the hub–filament system, the intensity gradient and the magnetic field are parallel whereas they tend to be perpendicular when penetrating the dense filaments and hub. Analysis of the |δ|- and ΣB-maps indicates that, in general, the magnetic field cannot prevent gravitational collapse, both east and west, suggesting that the magnetic field is initially dragged by the infalling motion and aligned with it, or is channeling material toward the central ridge from both sides. Values of ΣB ≳ 1 are found toward a north–south ridge encompassing the dust emission peak, indicating that in this region magnetic field dominates over gravity force, or that with the current angular resolution we cannot resolve a hypothetically more complex structure. We estimated the magnetic field strength, the mass-to-flux ratio, and the Alfvén Mach number, and found differences between the two hubs., [Conclusions] The different levels of fragmentation observed in these two hubs could arise from differences in the properties of the magnetic field rather than from differences in the intensity of the gravitational field because the density in the two hubs is similar. However, environmental effects could also play a role., This material is based upon work at the Caltech Submillimeter Observatory, which is operated by the California Institute of Technology. N.AL. acknowledges support from Ministery of Science and Innovation fellowship for predoctoral contracts in Spain and Ministery of Science and Technology (MoST) Summer Program in Taiwan for Spanish Graduate Student. N.AL., G.B., and J.M.G. are supported by the Spanish grant AYA2017-84390-C2-R (AEI/FEDER, UE). P.M.K. acknowledges support from Ministery of Science and Technology (MoST) grants MOST 108-2112-M-001-012 and MOST 109-2112-M-001-022 in Taiwan, and from an Academia Sinica Career Development Award. H.B.L. is supported by the Ministry of Science and Technology (MoST) of Taiwan (Grant MOST. 108-2112-M-001-002-MY3). P.T.P.H. is supported by Ministry of Science and Technology (MoST) of Taiwan Grant MOST 108-2112-M-001-016-MY1. A.P. acknowledges financial support from CONACyT and UNAM-PAPIIT IN113119 grant, México.

The alignment of dust grains with the ambient magnetic field produces polarization of starlight as well as thermal dust emission. Using the archival SOFIA/HAWC+ polarimetric data observed toward $\rho$ Ophiuchus (Oph) A cloud hosted by a B association star at 89 $\mu$m and 154 $\mu$m, we find that the fractional polarization of thermal dust emission first increases with the grain temperature and then decreases once the grain temperature exceeds $\simeq$ 25-32 K. The latter trend differs from the prediction of the popular RAdiative Torques (RATs) alignment theory which implies a monotonic increase of the polarization fraction with the grain temperature. We perform numerical modeling of polarized dust emission for the $\rho$ Oph-A cloud and calculate the degree of dust polarization by simultaneously considering the dust grain alignment and rotational disruption by RATs. Our modeling results could successfully reproduce both the rising and declining trends of the observational data. Moreover, we show that the alignment of only silicate grains or a mixture of silicate-carbon grains within a composite structure can reproduce the observational trends, assuming that all dust grains follow a power-law size distribution. Although there are a number of simplifications and limitations to our modeling, our results suggest grains in $\rho$ Oph-A cloud have a composite structure, and the grain size distribution has steeper slope than the standard size distribution for the interstellar medium. Combination of SOFIA/HAWC+ data with JCMT observations 450 $\mu$m and 850 $\mu$m would be useful to test the proposed scenario based on grain alignment and disruption by RATs., Comment: 14 pages, 12 figures, 1 table, accepted to ApJ

Genomic characterization of patients with myeloproliferative neoplasms (MPN) may lead to better diagnostic classification, prognostic assessment, and treatment decisions. These goals are particularly important in myelofibrosis (MF). We performed target Next Generation Sequencing for a panel of 255 genes and Chromosome Microarray Analysis (CMA) in 27 patients with MF. Patients were classified according to genomic findings and we compared the performance of a personalized prognostication system with IPSS, MIPSS70 and MIPSS70 + v2. Twenty-six patients presented mutations: 11.1% had single driver mutations in either JAK2, CALR or MPL; 85.2% had mutations in non-restricted genes (median: 2 per patient). CMA was abnormal in 91.7% of the 24 cases with available data. Copy-Number-Neutral Loss-of-Heterozygosity was the most common finding (66.7%). Del13q was the most frequent copy number variation, and we could define a 2.4 Mb minimally affected region encompassing RB1, SUCLA2 and CLLS2 loci. The largest genomic subgroup consisted of patients with mutations in genes involved with chromatin organization and splicing control (40.7%) and the personalized system showed better concordance and accuracy than the other prognostic systems. Comprehensive genomic characterization reveals the striking genetic complexity of MF and, when combined with clinical data, led, in our cohort, to better prognostication performance.

Carbon dioxide ( C O 2 ) is an undesirable component present in natural gas composition. The supersonic separator is a new and potential technology for natural gas treatment, which expands the gas through supersonic velocities until a shock wave formation. The modeling capacity to predict the shock wave position inside the device is analyzed considering parametric uncertainties. Results from four real gas models were compared in computational fluid dynamic modeling. Uncertainties that affect coefficients in the real gas models were propagated through the carbon dioxide flow solver using the Latin Hypercube Sampling approach. It was observed that the shock wave introduces non-linearity in the local standard deviation. Soave-Redlich-Kwong and Aungier-Redlich-Kwong are slightly affected by input parametric uncertainties. On the other hand, the Peng-Robinson model results are strongly affected.

SOFIA HAWC+ polarimetry at $154~\micron$ is reported for the face-on galaxy M51 and the edge-on galaxy NGC 891. For M51, the polarization vectors generally follow the spiral pattern defined by the molecular gas distribution, the far-infrared (FIR) intensity contours, and other tracers of star formation. The fractional polarization is much lower in the FIR-bright central regions than in the outer regions, and we rule out loss of grain alignment and variations in magnetic field strength as causes. When compared with existing synchrotron observations, which sample different regions with different weighting, we find the net position angles are strongly correlated, the fractional polarizations are moderately correlated, but the polarized intensities are uncorrelated. We argue that the low fractional polarization in the central regions must be due to significant numbers of highly turbulent segments across the beam and along lines of sight in the beam in the central 3 kpc of M51. For NGC 891, the FIR polarization vectors within an intensity contour of 1500 $\rm{MJy~sr^{-1}}$ are oriented very close to the plane of the galaxy. The FIR polarimetry is probably sampling the magnetic field geometry in NGC 891 much deeper into the disk than is possible with NIR polarimetry and radio synchrotron measurements. In some locations in NGC 891 the FIR polarization is very low, suggesting we are preferentially viewing the magnetic field mostly along the line of sight, down the length of embedded spiral arms. There is tentative evidence for a vertical field in the polarized emission off the plane of the disk., Comment: AJ, Accepted, In Press

We report on polarimetric maps made with HAWC+/SOFIA toward Rho Oph A, the densest portion of the Rho Ophiuchi molecular complex. We employed HAWC+ bands C (89 $��$m) and D (154 $��$m). The slope of the polarization spectrum was investigated by defining the quantity R_DC = p_D/p_C, where p_C and p_D represent polarization degrees in bands C and D, respectively. We find a clear correlation between R_DC and the molecular hydrogen column density across the cloud. A positive slope (R_DC > 1) dominates the lower density and well illuminated portions of the cloud, that are heated by the high mass star Oph S1, whereas a transition to a negative slope (R_DC < 1) is observed toward the denser and less evenly illuminated cloud core. We interpret the trends as due to a combination of: (1) Warm grains at the cloud outskirts, which are efficiently aligned by the abundant exposure to radiation from Oph S1, as proposed in the radiative torques theory; and (2) Cold grains deep in the cloud core, which are poorly aligned due to shielding from external radiation. To assess this interpretation, we developed a very simple toy model using a spherically symmetric cloud core based on Herschel data, and verified that the predicted variation of R_DC is consistent with the observations. This result introduces a new method that can be used to probe the grain alignment efficiency in molecular clouds, based on the analysis of trends in the far-infrared polarization spectrum., Accepted by ApJ (July 18 2019)

We compare the magnetic field orientation for the young giant molecular cloud Vela C inferred from 500-$\mu$m polarization maps made with the BLASTPol balloon-borne polarimeter to the orientation of structures in the integrated line emission maps from Mopra observations. Averaging over the entire cloud we find that elongated structures in integrated line-intensity, or zeroth-moment maps, for low density tracers such as $^{12}$CO and $^{13}$CO $J$ $\rightarrow$ 1 - 0 are statistically more likely to align parallel to the magnetic field, while intermediate or high density tracers show (on average) a tendency for alignment perpendicular to the magnetic field. This observation agrees with previous studies of the change in relative orientation with column density in Vela C, and supports a model where the magnetic field is strong enough to have influenced the formation of dense gas structures within Vela C. The transition from parallel to no preferred/perpendicular orientation appears to happen between the densities traced by $^{13}$CO and by C$^{18}$O $J$ $\rightarrow$ 1 - 0. Using RADEX radiative transfer models to estimate the characteristic number density traced by each molecular line we find that the transition occurs at a molecular hydrogen number density of approximately $10^3$ cm$^{-3}$. We also see that the Centre-Ridge (the highest column density and most active star-forming region within Vela C) appears to have a transition at a lower number density, suggesting that this may depend on the evolutionary state of the cloud., Comment: 27 pages, 15 figures, accepted for publication in ApJ

We report the first detection of galactic spiral structure by means of thermal emission from magnetically aligned dust grains. Our 89 $��$m polarimetric imaging of NGC 1068 with the High-resolution Airborne Wideband Camera/Polarimeter (HAWC+) on NASA's Stratospheric Observatory for Infrared Astronomy (SOFIA) also sheds light on magnetic field structure in the vicinity of the galaxy's inner-bar and active galactic nucleus (AGN). We find correlations between the 89 $��$m magnetic field vectors and other tracers of spiral arms, and a symmetric polarization pattern as a function of the azimuthal angle arising from the projection and inclination of the disk field component in the plane of the sky. The observations can be fit with a logarithmic spiral model with pitch angle of $16.9^{+2.7}_{-2.8}$$^{\circ}$ and a disk inclination of $48\pm2^{\circ}$. We infer that the bulk of the interstellar medium from which the polarized dust emission originates is threaded by a magnetic field that closely follows the spiral arms. Inside the central starburst disk ($, 13 pages, 7 figures, Accepted for publication by ApJ

Linear polarization maps of the Carina Nebula were obtained at 250, 350, and 500 $\mu$m during the 2012 flight of the BLASTPol balloon-borne telescope. These measurements are combined with Planck 850 $\mu$m data in order to produce a submillimeter spectrum of the polarization fraction of the dust emission, averaged over the cloud. This spectrum is flat to within $\pm$15% (relative to the 350 $\mu$m polarization fraction). In particular, there is no evidence for a pronounced minimum of the spectrum near 350 $\mu$m, as suggested by previous ground-based measurements of other molecular clouds. This result of a flat polarization spectrum in Carina is consistent with recently-published BLASTPol measurements of the Vela C molecular cloud, and also agrees with a published model for an externally-illuminated, dense molecular cloud by Bethell and collaborators. The shape of the spectrum in Carina does not show any dependence on the radiative environment of the dust, as quantified by the Planck-derived dust temperature or dust optical depth at 353 GHz., Comment: 13 pages, 12 figures, submitted to ApJ

High-resolution Airborne Wide-band Camera (HAWC[Formula: see text]) is the facility far-infrared imager and polarimeter for SOFIA, NASA’s Stratospheric Observatory for Infrared Astronomy. It is designed to cover the portion of the infrared spectrum that is completely inaccessible to ground-based observatories and which is essential for studies of astronomical sources with temperatures between tens and hundreds of degrees Kelvin. Its ability to make polarimetric measurements of aligned dust grains provides a unique new capability for studying interstellar magnetic fields. HAWC[Formula: see text] began commissioning flights in April 2016 and was accepted as a facility instrument in early 2018. In this paper, we describe the instrument, its operational procedures, and its performance on the observatory.

We present observations of NGC 1068 covering the $19.7-53.0$ $\mu$m wavelength range using FORCAST and HAWC+ onboard SOFIA. Using these observations, high-angular resolution infrared (IR) and sub-mm observations, we find an observational turn-over of the torus emission in the $30-40$ $\mu$m wavelength range with a characteristic temperature of $70-100$ K. This component is clearly different from the diffuse extended emission in the narrow line and star formation regions at 10-100 $\mu$m within the central 700 pc. We compute $2.2-432$ $\mu$m 2D images using the best inferred \textsc{clumpy} torus model based on several nuclear spectral energy distribution (SED) coverages. We find that when $1-20$ $\mu$m SED is used, the inferred result gives a small torus size ($, Comment: 12 pages, 7 Figures, Accepted for publication in ApJ

We present Far-Infrared polarimetry observations of M82 at 53 and $154~\mu \rm{m}$ and NGC 253 at $89~\mu \rm{m}$, which were taken with HAWC+ in polarimetry mode on the Stratospheric Observatory for Infrared Astronomy (SOFIA). The polarization of M82 at $53~\mu \rm{m}$ clearly shows a magnetic field geometry perpendicular to the disk in the hot dust emission. For M82 the polarization at $154~\mu \rm{m}$ shows a combination of field geometry perpendicular to the disk in the nuclear region, but closer to parallel to the disk away from the nucleus. The fractional polarization at $53~\mu \rm{m}$ $(154~\mu \rm{m})$ ranges from 7% (3%) off nucleus to 0.5% (0.3%) near the nucleus. A simple interpretation of the observations of M82 invokes a massive polar outflow, dragging the field along, from a region $\sim 700$~pc in diameter that has entrained some of the gas and dust, creating a vertical field geometry seen mostly in the hotter $(53~\mu \rm{m})$ dust emission. This outflow sits within a larger disk with a more typical planar geometry that more strongly contributes to the cooler $(154~\mu \rm{m})$ dust emission. For NGC 253, the polarization at $89~\mu \rm{m}$ is dominated by a planar geometry in the tilted disk, with weak indication of a vertical geometry above and below the plane from the nucleus. The polarization observations of NGC 253 at $53~\mu \rm{m}$ were of insufficient S/N for detailed analysis., Comment: 6 Figures, 20 pages, ApJL accepted

Polarized emission from aligned dust is a crucial tool for studies of magnetism in the ISM and a troublesome contaminant for studies of CMB polarization. In each case, an understanding of the significance of the polarization signal requires well-calibrated physical models of dust grains. Despite decades of progress in theory and observation, polarized dust models remain largely underconstrained. During its 2012 flight, the balloon-borne telescope BLASTPol obtained simultaneous broad-band polarimetric maps of a translucent molecular cloud at 250, 350, and 500 microns. Combining these data with polarimetry from the Planck 850 micron band, we have produced a submillimeter polarization spectrum for a cloud of this type for the first time. We find the polarization degree to be largely constant across the four bands. This result introduces a new observable with the potential to place strong empirical constraints on ISM dust polarization models in a previously inaccessible density regime. Comparing with models by Draine and Fraisse (2009), our result disfavors two of their models for which all polarization arises due only to aligned silicate grains. By creating simple models for polarized emission in a translucent cloud, we verify that extinction within the cloud should have only a small effect on the polarization spectrum shape compared to the diffuse ISM. Thus we expect the measured polarization spectrum to be a valid check on diffuse ISM dust models. The general flatness of the observed polarization spectrum suggests a challenge to models where temperature and alignment degree are strongly correlated across major dust components., Comment: 17 pages, 10 figures. Submitted to ApJ

We report new polarimetric and photometric maps of the massive star-forming region OMC-1 using the HAWC+ instrument on the Stratospheric Observatory for Infrared Astronomy (SOFIA). We present continuum polarimetric and photometric measurements of this region at 53, 89, 154, and 214 microns at angular resolutions of 5.1, 7.9, 14.0, and 18.7 arcseconds for the four bands, respectively. The photometric maps enable the computation of improved SEDs for the region. We find that at the longer wavelengths, the inferred magnetic field configuration matches the `hourglass' configuration seen in previous studies, indicating magnetically-regulated star formation. The field morphology differs at the shorter wavelengths. The magnetic field inferred at these wavelengths traces the bipolar structure of the explosive Becklin-Neugebauer (BN)/Kleinman-Low (KL) outflow emerging from OMC-1 behind the Orion Nebula. Using statistical methods to estimate the field strength in the region, we find that the explosion dominates the magnetic field near the center of the feature. Farther out, the magnetic field is close to energetic equilibrium with the ejecta and may be providing confinement to the explosion. The correlation between polarization fraction and the local polarization angle dispersion indicates that the depolarization as a function of unpolarized intensity is a result of intrinsic field geometry as opposed to decreases in grain alignment efficiency in denser regions., Comment: 28 pages, 14 figures, ApJ, accepted

We statistically evaluate the relative orientation between gas column density structures, inferred from Herschel submillimetre observations, and the magnetic field projected on the plane of sky, inferred from polarized thermal emission of Galactic dust observed by BLASTPol at 250, 350, and 500 micron, towards the Vela C molecular complex. First, we find very good agreement between the polarization orientations in the three wavelength-bands, suggesting that, at the considered common angular resolution of 3.0 arcminutes that corresponds to a physical scale of approximately 0.61 pc, the inferred magnetic field orientation is not significantly affected by temperature or dust grain alignment effects. Second, we find that the relative orientation between gas column density structures and the magnetic field changes progressively with increasing gas column density, from mostly parallel or having no preferred orientation at low column densities to mostly perpendicular at the highest column densities. This observation is in agreement with previous studies by the Planck collaboration towards more nearby molecular clouds. Finally, we find a correspondence between the trends in relative orientation and the shape of the column density probability distribution functions. In the sub-regions of Vela C dominated by one clear filamentary structure, or "ridges", we find a sharp transition from preferentially parallel or having no preferred relative orientation at low column densities to preferentially perpendicular at highest column densities. In the sub-regions of Vela C dominated by several filamentary structures with multiple orientations, or "nests", such a transition is also present, but it is clearly less sharp than in the ridge-like sub-regions. Both of these results suggest that the magnetic field is dynamically important for the formation of density structures in this region., Comment: 16 pages, 17 figures. Submitted to A&A

Context. Magnetic fields can affect significantly the star formation process. The theory of the magnetically-driven collapse in a uniform field predicts that initially the contraction happens along the field lines. When the gravitational pull grows strong enough, the magnetic field lines pinch inwards, giving rise to a characteristic hourglass shape. Aims. We investigate the magnetic field structure of a young Class 0 object, IRAS 15398-3359, embedded in the Lupus I cloud. Previous observations at large scales suggest that this source evolved in an highly magnetised environment. This object thus appears an ideal candidate to study the magnetically driven core collapse in the low-mass regime. Methods. We have performed polarisation observations of IRAS 15398-3359 at 214$\mu$m using the SOFIA/HAWC+ instrument, thus tracing the linearly polarised thermal emission of cold dust. Results. Our data unveil a significant bend of the magnetic field lines due to the gravitational pull. The magnetic field appears ordered and aligned with the large-scale B-field of the cloud and with the outflow direction. We estimate a magnetic field strength of $B= 78 \mu$G, expected to be accurate within a factor of two. The measured mass-to-flux parameter is $\lambda= 0.95$, indicating that the core is in a transcritical regime., Comment: Accepted for publication in A&A on 12/10/19

The Direct Dual Quadrature Method of Generalized Moments (D2uQMoGeM) was formulated for the solution of the population balance equation. It mixes the properties of the Direct Quadrature Method of Moments (DQMoM) and the Dual Quadrature Method of Generalized Moments (DuQMoGeM). The weights and weighted abscissas are tracking directly as in DQMoM and the quadrature errors are controlled by an adaptive quadrature as in DuQMoGeM. The D2uQMoGeM was implemented and tested for several different problems with analytical solutions. It was shown to be more accurate than DQMoM with a reasonable increase in computational time.

We present a large-scale combination of near-infrared (near-IR) interstellar polarization data from background starlight with polarized emission data at submillimeter (sub-mm) wavelengths for the Vela C molecular cloud. The near-IR data consist of more than 6700 detections probing a range of visual extinctions between $2$ and $20\,$mag in and around the cloud. The sub-mm data was collected in Antartica by the Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol). This is the first direct combination of near-IR and sub-mm polarization data for a molecular cloud aimed at measuring the "polarization efficiency ratio" ($R_{\mathrm{eff}}$), a quantity that is expected to depend only on grain intrinsic physical properties. It is defined as $p_{500}/(p_{I}/\tau_{V})$, where $p_{500}$ and $p_{I}$ are polarization fractions at $500\,\mu$m and $I$-band, respectively, and $\tau_{V}$ is the optical depth. To ensure that the same column density of material is producing both polarization from emission and from extinction, we conducted a careful selection of near-background stars using 2MASS, $Herschel$ and $Planck$ data. This selection excludes objects contaminated by the Galactic diffuse background material as well as objects located in the foreground. Accounting for statistical and systematic uncertainties, we estimate an average $R_{\mathrm{eff}}$ value of $2.4\pm0.8$, which can be used to test the predictions of dust grain models designed for molecular clouds when such predictions become available. $R_{\mathrm{eff}}$ appears to be relatively flat as a function of the cloud depth for the range of visual extinctions probed., Comment: 23 pages, accepted by the Astrophysical Journal

We carried out an optical polarimetric study in the direction of the RCW95 star forming region in order to probe the sky-projected magnetic field structure by using the distribution of linear polarization segments which seem to be well aligned with the more extended cloud component. A mean polarization angle of $\theta=49.8^o\pm7.7^o$ was derived. Through the spectral dependence analysis of polarization it was possible to obtain the total-to-selective extinction ratio ($R_V$) by fitting the Serkowski function, resulting in a mean value of $R_V=2.93\pm0.47$. The foreground polarization component was estimated and is in agreement with previous studies in this direction of the Galaxy. Further, near-infrared images from Vista Variables in the Via L\'actea (VVV) survey were collected to improve the study of the stellar population associated with the HII region. The Automated Stellar Cluster Analysis (ASteCA) algorithm was employed to derive structural parameters for two clusters in the region, and a set of PAdova and TRieste Stellar Evolution Code (PARSEC) isochrones was superimposed on the decontaminated colour-magnitude diagrams (CMDs) to estimate an age of about 3 Myr for both clusters. Finally, from the near-infrared photometry study combined with spectra obtained with the Ohio State Infrared Imager and Spectrometer (OSIRIS) mounted at the Southern Astrophysics Research Telescope (SOAR) we derived the spectral classification of the main ionizing sources in the clusters associated with IRAS 15408$-$5356 and IRAS 15412$-$5359, both objects classified as O4 V stars., Comment: 14 pages, 16 figures

NPM1 heterozygous mutations are present in roughly a third of patients with acute myeloid leukemia (AML), making it one of the most frequent genomic alterations in these patients.1 The mutations are characterized by frameshift insertions in the region encoding the C-terminus of the protein, leading to the disruption of tryptophan residues 288 and 290 and the generation of an additional nuclear export signal (NES) motif, that ultimately leads to the cytoplasmic localization of the mutated NPM1 (NPM1m) as well as wild-type (WT) NPM1 proteins.2

Polarization maps of the Vela C molecular cloud were obtained at 250, 350, and 500um during the 2012 flight of the balloon-borne telescope BLASTPol. These measurements are used in conjunction with 850um data from Planck to study the submillimeter spectrum of the polarization fraction for this cloud. The spectrum is relatively flat and does not exhibit a pronounced minimum at \lambda ~350um as suggested by previous measurements of other molecular clouds. The shape of the spectrum does not depend strongly on the radiative environment of the dust, as quantified by the column density or the dust temperature obtained from Herschel data. The polarization ratios observed in Vela C are consistent with a model of a porous clumpy molecular cloud being uniformly heated by the interstellar radiation field., Comment: 9 pages, 11 figures

The G14.225-0.506 infrared dark cloud (IRDC G14.2) displays a remarkable complex of parallel dense molecular filaments projected on the plane of the sky. Previous dust emission and molecular-line studies have speculated whether magnetic fields could have played an important role in the formation of such long-shaped structures, which are hosts to numerous young stellar sources. In this work we have conducted a vast polarimetric survey at optical and near-infrared wavelengths in order to study the morphology of magnetic field lines in IRDC G14.2 through the observation of background stars. The orientation of interstellar polarization, which traces magnetic field lines, is perpendicular to most of the filamentary features within the cloud. Additionally, the larger-scale molecular cloud as a whole exhibits an elongated shape also perpendicular to magnetic fields. Estimates of magnetic field strengths indicate values in the range $320 - 550\,\mu$G, which allows sub-alfv\'enic conditions, but does not prevent the gravitational collapse of hub-filament structures, which in general are close to the critical state. These characteristics suggest that magnetic fields played the main role in regulating the collapse from large to small scales, leading to the formation of series of parallel elongated structures. The morphology is also consistent with numerical simulations that show how gravitational instabilities develop under strong magnetic fields. Finally, the results corroborate the hypothesis that a strong support from internal magnetic fields might explain why the cloud seems to be contracting on a time scale 2-3 times larger than what is expected from a free-fall collapse., Comment: Accepted for publication at The Astrophysical Journal

Polarized thermal emission from interstellar dust grains can be used to map magnetic fields in star forming molecular clouds and the diffuse interstellar medium (ISM). The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) flew from Antarctica in 2010 and 2012 and produced degree-scale polarization maps of several nearby molecular clouds with arcminute resolution. The success of BLASTPol has motivated a next-generation instrument, BLAST-TNG, which will use more than 3000 linear polarization sensitive microwave kinetic inductance detectors (MKIDs) combined with a 2.5m diameter carbon fiber primary mirror to make diffraction-limited observations at 250, 350, and 500 $\mu$m. With 16 times the mapping speed of BLASTPol, sub-arcminute resolution, and a longer flight time, BLAST-TNG will be able to examine nearby molecular clouds and the diffuse galactic dust polarization spectrum in unprecedented detail. The 250 $\mu$m detector array has been integrated into the new cryogenic receiver, and is undergoing testing to establish the optical and polarization characteristics of the instrument. BLAST-TNG will demonstrate the effectiveness of kilo-pixel MKID arrays for applications in submillimeter astronomy. BLAST-TNG is scheduled to fly from Antarctica in December 2017 for 28 days and will be the first balloon-borne telescope to offer a quarter of the flight for "shared risk" observing by the community., Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VIII, June 29th, 2016

Figure 2 in the original manuscript displays the polarization efficiency for the optical, near infrared and sub-millimeter (submm) polarimetric data as P/AV, where P is the polarization degree and AV is the visual extinction traced by the data. However, the polarization efficiency for the submm data should be simply P. By dividing P by AV, we obtain a steeper and wrong slope for the decrease in polarization efficiency. The suitable form for Fig. 2 of the original document is exhibited in Fig. 1 of the present corrigendum. The submm polarization efficiency decreases as ~−1.0 with respect to AV, instead of the originally published ~−2.0. Although the decrease in polarization efficiency at the submm regime is shallower than originally proposed, our modelling of the polarization degree with respect to the relative intensity, I/Imax, still predicts the detection of a polarization hole (Sect. 3 of the published manuscript). Therefore, the main conclusions are unchanged.

The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) was a suborbital experiment designed to map magnetic fields in order to study their role in star formation processes. BLASTPol made detailed polarization maps of a number of molecular clouds during its successful flights from Antarctica in 2010 and 2012. We present the next-generation BLASTPol instrument (BLAST-TNG) that will build off the success of the previous experiment and continue its role as a unique instrument and a test bed for new technologies. With a 16-fold increase in mapping speed, BLAST-TNG will make larger and deeper maps. Major improvements include a 2.5-m carbon fiber mirror that is 40% wider than the BLASTPol mirror and ~3000 polarization sensitive detectors. BLAST-TNG will observe in three bands at 250, 350, and 500 μm. The telescope will serve as a pathfinder project for microwave kinetic inductance detector (MKID) technology, as applied to feedhorn-coupled submillimeter detector arrays. The liquid helium cooled cryostat will have a 28-day hold time and will utilize a closed-cycle 3 He refrigerator to cool the detector arrays to 270 mK. This will enable a detailed mapping of more targets with higher polarization resolution than any other submillimeter experiment to date. BLAST-TNG will also be the first balloon-borne telescope to offer shared risk observing time to the community. This paper outlines the motivation for the project and the instrumental design.

[Aims] We aim to investigate the polarization properties of a starless core in an early evolutionary stage. Linear polarization data reveal the properties of the dust grains in the distinct phases of the interstellar medium. Our goal is to investigate how the polarization degree and angle correlate with the cloud and core gas., [Methods] We use optical, near infrared, and submillimeter polarization observations on the starless object Pipe-109 in the Pipe nebula. Our data cover a physical scale range of 0.08 to 0.4 pc, comprising the dense gas, envelope, and the surrounding cloud., [Results] The cloud polarization is well traced by the optical data. The near infrared polarization is produced by a mixed population of grains from the core border and the cloud gas. The optical and near infrared polarization toward the cloud reaches the maximum possible value and saturates with respect to the visual extinction. The core polarization is predominantly traced by the submillimeter data and has a steep decrease with respect to the visual extinction. Modeling of the submillimeter polarization indicates a magnetic field main direction projected onto the plane-of-sky and loss of grain alignment for densities higher than 6 × 104 cm-3 (or AV> 30 mag)., [Conclusions] The object is immersed in a magnetized medium with a very ordered magnetic field. The absence of internal source of radiation significantly affects the polarization efficiencies in the core, creating a polarization hole at the center of the starless core. This result supports the theory of dust grain alignment via radiative torques., F.O.A. acknowledges financial support from the BMBF Verbundforschung 05A11PD3 project. G.A.P.F. and F.P.S. acknowledge support from the Brazilian agencies CNPq, CAPES and FAPEMIG. F.P.S. is supported by the CAPES grant 2397/13-7. P.F. is supported by the Spanish CONSOLIDER project CSD2009-00038. P.F. and J.M.G. are supported by the Spanish MINECO AYA2011-30228-C03-02, and Catalan AGAUR 2009SGR1172 grants.

The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) is a suborbital mapping experiment designed to study the role magnetic fields play in star formation. BLASTPol has had two science flights from McMurdo Station, Antarctica in 2010 and 2012. These flights have produced thousands of polarization vectors at 250, 350 and 500 microns in several molecular cloud targets. We present the design, specifications, and progress towards the next-generation BLASTPol experiment (BLAST-TNG). BLAST-TNG will fly a 40% larger diameter primary mirror, with almost 8 times the number of polarization-sensitive detectors resulting in a factor of 16 increase in mapping speed. With a spatial resolution of 22 arcseconds and four times the field of view of BLASTPol, BLAST-TNG will bridge the angular scales between Planck's low resolution all-sky maps and ALMA's ultra-high resolution narrow fields. The new receiver has a larger cryogenics volume, allowing for a 28 day hold time. BLAST-TNG employs three arrays of Microwave Kinetic Inductance Detectors (MKIDs) with 30% fractional bandwidth at 250, 350 and 500 microns. In this paper, we will present the new BLAST-TNG instrument and science objectives., 12 pages, 6 figures. Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 9145

Vários estudos demonstram que as mulheres apresentam mais dor do que os homens. Entretanto, os estudos sobrelombalgia e dor torácica não são conclusivos. Em casos de dores articulares e fibromialgia existe aumento da prevalência com o progredir das idades em ambos os sexos, apesar de haver predominio nas mulheres. As síndromes dolorosas decorrentes das disfunções têmporo-mandibulares são mais comuns nas mulheres que nos homens e apresentam pico de ocorrência nas fases reprodutivas. A diferença na ocorrência da dor nos homens e nas mulheres pode ser devida a vários fatores incluindo os constitucionais, os hormonais, os cognitivos e os culturais, entre outros. O aumento da freqüência da dor com o avanço da idade, especialmente das dores articulares e da fibromialgia, sugere haver associação entre as afecções degenerativas ou acúmulo de casos de dor com o progredir da idade. A redução da freqüência de alguns casos de dor nos idosos pode ser devida à melhora das condições causais com o passar do tempo ou ao aumento da incapacidade ou da mortalidade que remove tais indivíduos das comunidades.

O câncer colorretal (CCR) é uma das neoplasias de maior importância atualmente, tanto por sua prevalência como por sua incidência, correspondendo a 10% de todas as neoplasias nos EUA. Contudo, nos últimos 50 anos, sua mortalidade permaneceu praticamente inalterada. Desde que Morson, em 1978, descreveu pela primeira vez a seqüênciaadenoma-carcinoma, a elucidação da genética molecular envolvida na patogênese do CCR passou a ser estudada intensamente e muitos avanços foram obtidos. Vários genes como APC, DCC e p53, entre outros, foram identificados como participantes da seqüência adenoma-carcinoma, estando envolvidos na gênese tumoral baseada na teoria de múltiplos passos, onde o acúmulo de mutações genéticas em células instáveis é o fator principal que acaba por originar o câncer. Há dois tipos básicos de CCR: o esporádico, que corresponde a 85% do total de casos de CCR; e o familiar, com cerca de 15% dos casos e destaque para a Polipose Adenomatosa Familiar (PAF) e o Câncer Colorretal Hereditário não-poliposo (HNPCC). As pesquisas atuais vêm decifrando o mecanismo de ação de tais genes, buscando determinar a importância e valor prognóstico dos mesmos. Espera-se que a elucidação completa de tais mecanismos permita uma diminuição não só da mortalidade do CCR, mas também do impacto social imposto por tal doença. Ademais, a elaboraçãode tratamentos alternativos à cirurgia parece possível, através da terapia genética. Portanto, familiarizar-se com a Genética do Câncer Colorretal e os avanços nessa área torna-se imperativo para clínicos e cirurgiões da área digestiva.

Introduction: The number of patients who have undergone organ and bone marrow transplantation continues to increase, as does long-term survival. Post-transplant lymphoproliferative disorders (PTLD) are potentially life-threatening complications after solid organ transplantation. Epstein-Barr virus (EBV) infection that leads to uncontrolled B cell proliferation and tumor formation. PTLD is relatively common malignancy after transplantation and is seen up to 10% of all solid organ transplant recipients, and varies considerably among the different types of organs transplanted. We sought to determine incidence and mortality risk of PTLD in recipients of Hospital Israelita Albert Einstein, Sao Paulo, Brazil. Patient and Methods: We conducted a retrospective observational study of 3006 recipients of lung, kidney, liver, pancreas, heart and bone marrow between 2002 and 2015. A total of 26 cases (0.8%) of PTLD were identified in 3006 transplants. Kaplan-Meier analysis was performed for PTLD patient survival after PTLD. Results: Median interval from transplantation to diagnosis was 49 (4-150) months. Median age was 49 years (12-73) and 73% were men. Histological subgroups included: Monomorphic PTLD (50%), Hodgkin Lymphoma (11,5%), Burkitt (15,3%), Anaplastyc large cell (7,6%) and Plasmacytic Hyperplasia (15,3%). Sixteen patients (61,5%) were EBV (+) and eleven (42,3%) were IPI III-IV only two had bone marrow infiltration. Treatment of PTLD varied according to stage and clinical circumstances: six patients (23%) were treated with Rituximab only and seventeen (65,3%) treated with R-chemotherapy. Nine (34,6%) patients died. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival, since 5 patients remain alive. The median overall survival was 1260 days, and 2-years overall survival was 65,4%. Conclusion: PTLD after solid organs transplantation remains a challenge as a result of its frequency, complexity and disappointing outcome. We found a paucity of early onset PTLD in our cohort with only one case in the first posttransplant year. Potential contributing factors included a high prevalence of previous EBV virus exposure. The rate of PTLD malignancies in our group is comparable to that reported in other centers in Europe and North American, since it is the largest series reported by a single institution in South America. Consistent with the known antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival. Disclosures No relevant conflicts of interest to declare.

Purpose PCNSL standard treatment encompass 2 phases: induction and consolidation. Induction consists of high-dose methotrexate-based polychemotherapy for most patients and consolidation is still to be defined. ASCT is an effective treatment and despite the advancements in this technique for other disease sites, its role in PCNSL remains unclear. This systematic review aims to evaluate toxicity and outcomes of ASCT as upfront treatment in PNCSL. Material and Methods In accordance to PRISMA guidelines, a systematic review of the literature was conducted on studies reporting ASCT in PCNSL. EMBASE, MEDLINE and Cochrane databases were systematically searched for relevant studies until May 2016. All clinical trials (CT) evaluating the role of ASCT as up front treatment for PCNSL (excluding recurrence or salvage) were included. Studies were classified into 2 groups for statistical analysis: (1) Regimens containing thiotepa (either on induction or intensification regimen or conditioning regimen; (2) Regimens without thiotepa. Dichotomous outcomes were summarized as risk ratios (RRs). The size effect of the intervention for time-to-event outcomes was calculated by the pooled hazard ratio (HR), followed by the confidence interval (CI) of 95%. For determining derivative of expected events, the Z-Score for two-tailed p-value was calculated based on relative risk of each study. Results From 1803 references, 7 articles (6 phase 2; 1 pilot trial) from 2006 to 2016 were selected, comprising a total of 181 patients. For up front treatment of PCNSL with ASCT regimens containing thiotepa plus or minus WBRT: total of 128 patients were identified in 5 studies. Patient's median age was 54,5 (range, 54 to 57), KPS ranged from 70 to 90, WBRT was allowed in 3 studies and a median of 81% of the patients completes the ASCT protocol. Median complete response rate (CRR) was 69% (range, 54 to 81%), 2-years progression free survival (2PFS) 69% (range, 54 to 81%) and 2-years overall survival (2OS) 84% ranging from 83 to 91% in a median follow-up time of 15 to 63 months. Median neurotoxicity rates (NR) and treatment related mortality (TRM) were 3% (0 to 33%) and 3% (0 to 13%), respectively. (2) Up front ASCT regimens without thiotepa plus or minus WBRT: total of 53 patients were identified in 2 studies. Patient's median age was 52,5 (range, 52 to 53), KPS ranged from 70 to 80, WBRT was allowed in 1 study and a median of 59% of the patients completes the ASCT protocol. Median CRR was 31% (range, 18 to 44%), 2PFS 44% (range, 25 to 62%), 2OS of 65% ranging from 60 to 70% in a median follow-up time of 28 to 34 months. Median NR and TRM were 4% (0 to 8%) and 4%, respectively. Regimens containing thiotepa were associated with better 2OS (RR 0.46; IC95 0.27 to 0.80; P=0.006; Z=2.76) and increased 2PFS (RR 0.52; IC95 0.37 to 0.74; P=0.0002; Z=3.69). The addition of WBRT wasn't associated with better 2OS (RR 0.94; IC95 0.53 to 1.67; P=0.082; Z=0.22) Conclusions Up front ASCT in the management of PCNSL is associated with high CRR and excellent 2OS and 2PFS when thiotepa is added to the regimen. Close to 200 patients treated in CT settings with up front ASCT for PCNSL were found in the literature and at least 4 different treatment scenarios were described. An important rate (>10%) of TRM was seen in two studies however ASCT was seem to be safe in most of the publications. Disclosures No relevant conflicts of interest to declare.

Introduction: There is an increase application of haploidentical stem cell transplantation (haplo-HSCT) based on post-transplant cyclophosphamide without T cells depletion in patients lacking identical HLA donor. One important issue in haplo-HSCT is related to immunosuppression and immune reconstitution, leading to infection complications. Objective: To analyze the incidence and risk factors of viral infections in patients undergoing haploidentical BMT in a single Brazilian Cancer Center. Methodology: We analyzed 31 consecutive patients with hematological malignancies (80%) and severe aplastic anemia, who underwent haplo-HSCT from 2010 to 2015. Nine patients (29%), 16 (51%), and 6 (19%) used myeloablative (MA), non-myeloablative (NMA) and reduced intensive conditioning (RIC) regimen, respectively. All grafts were T cell replete and 29 (93.5%) of the haplo-HSCT used GCSF-stimulated bone marrow source. All patients have received mycophenolate mofetil (MMF), tacrolimus, and post-transplant Cyclophosphamide (Cy) as post transplant immunosuppression. MMF was discontinued on D+35 in NMA regimen and on D+90 in MA and RIC regimen. Viral monitoring tests were performed from graft infusion to D+180 post transplant. Quantitative PCR for CMV and Adenovirus were performed weekly and quantitative PCR for EBV every 14 days. BK virus and HHV-6 quantitative PCR were performed only for patients with clinical suspicious. Besides daily absolute lymphocyte count, CD4+ T lymphocyte count was done on D+100 and D+180 post transplant. The event reactivation / viral infection was assessed in the first 6 months post haplo-HSCT. Results: Patients median age was 34 years (range, 7 to 74). The median graft CD34+ cells infused was 2,79 x106/kg (0,56 to 5,88x106/kg), time to MMF suspension was on D+41 (range 30 to 161) and median patients engraftment was on day 18 (13 to 34). All patients achieved full donor chimerism by D+28 to 34+ post transplant. The median number of lymphocytes on D+30 and D+100, was 223x103/ul and 705x103/ul respectively, and median number of CD4+ lymphocytes on the D+100 and D+180 was 108/mm3 and 158/mm3, respectively. The cumulative incidence of viral reactivation on D+180 was 85.7%. Mortality related to viral infection was 10% and the overall survival in 180 days 74.8%. Thirty patients were CMV IgG+ (96%) and only five donors (16.1%) were CMV IgG-. First CMV reactivation occurred in 24/31 (77,4%) patients, 33,3% (8/24) had subsequent CMV reactivations. The median time of CMV reactivation was on D+41 (21-67). Documented CMV pneumonia occurred in 3 patients. Time to MMF suspension was associated to CMV reactivation (P=0,043) and we found that suspension after day + 40 had higher risk of reactivation, with sensitivity of 62,5% and specificity of 71,4% (IC 95% 0,517 - 0,989, P=0.045; ROC curve). There was no association between CMV reactivation and conditioning regimen, age, number of CD34+ cells infused (Table 1). Interestingly, age presented a linear correlation for second reactivation with an increased risk of 6% per year (HR 1.06, IC95 [1.02 to 1.11]; P=0,007). CMV reactivation was not associated with greater risk of death (P=0,194). The second more frequent viral infection was BK virus cystitis (n=11, 35.5%) and was not correlated with increased death risk (P=0,573) or any other proposed predictors factors. Parvovirus B19 infection occurred in 4 patients (12%) and adenovirus reactivation in 3 (9%). All patients who had adenovirus reactivation also had CMV reactivation and BK virus cystitis. Median lymphocytes and CD4+ counts were similarly in patients with (p = 0.385) or no (P = 0.800) CMV reactivation. The incidence of grade II-IV acute GVHD was 25.8% and there was no correlation to viral reactivation (P=0,351) or time to MMF suspension (P=0,63). However, all patients with acute GVHD II-IV showed reactivation of CMV. Conclusion: CMV reactivations and infections in our setting seems to be higher than previously reported in the literature, probably because of high CMV IgG+ positive recipient/donor population in Brazil. Early MMF suspension (before D+40) is an effective and safe measure to control CMV reactivation in patients submitted to cy post haplo-HSCT. Disclosures No relevant conflicts of interest to declare.

We present the results of combined NH3(1,1) and (2,2) line emission observed with the Very Large Array and the Effelsberg 100m telescope of the Infrared Dark Cloud G14.225-0.506. The NH3 emission reveals a network of filaments constituting two hub-filament systems. Hubs are associated with gas of rotational temperature Trot \sim 25 K, non-thermal velocity dispersion ~1.1 km/s, and exhibit signs of star formation, while filaments appear to be more quiescent (Trot \sim 11 K, non-thermal velocity dispersion ~0.6 km/s). Filaments are parallel in projection and distributed mainly along two directions, at PA \sim 10 deg and 60 deg, and appear to be coherent in velocity. The averaged projected separation between adjacent filaments is between 0.5 pc and 1pc, and the mean width of filaments is 0.12 pc. Cores within filaments are separated by ~0.33 pc, which is consistent with the predicted fragmentation of an isothermal gas cylinder due to the 'sausage'-type instability. The network of parallel filaments observed in G14.225-0.506 is consistent with the gravitational instability of a thin gas layer threaded by magnetic fields. Overall, our data suggest that magnetic fields might play an important role in the alignment of filaments, and polarization measurements in the entire cloud would lend further support to this scenario., 6 pages, 4 figures. Accepted for publication on Astrophysical Journal Letters

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1ĝ€‰au is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 ut. The event is consistent with a spherical shape for Eris, with radius 1,163±6 kilometres, density 2.52±0.05 grams per cm 3 and a high visible geometric albedo,. No nitrogen, argon or methane atmospheres are detected with surface pressure larger than about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun. © 2011 Macmillan Publishers Limited. All rights reserved. Fil: Sicardy, B.. Universite Pierre et Marie Curie; Francia. Institut Universitaire de France; Francia Fil: Ortiz, J.L.. Consejo Superior de Investigaciones Científicas; España Fil: Assafin, M.. Universidade Federal do Rio de Janeiro; Brasil Fil: Jehin, E.. Université de Liège; Bélgica Fil: Maury, A.. San Pedro de Atacama Celestial Explorations; Chile Fil: Lellouch, E.. Universite Pierre et Marie Curie; Francia Fil: Gil Hutton, Ricardo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico ; Argentina Fil: Braga Ribas, F.. Universite Pierre et Marie Curie; Francia. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Colas, F.. Universite Pierre et Marie Curie; Francia Fil: Hestroffer, D.. Universite Pierre et Marie Curie; Francia Fil: Lecacheux, J.. Universite Pierre et Marie Curie; Francia Fil: Roques, F.. Universite Pierre et Marie Curie; Francia Fil: Santos-Sanz, P.. Universite Pierre et Marie Curie; Francia Fil: Widemann, T.. Universite Pierre et Marie Curie; Francia Fil: Morales, N.. Consejo Superior de Investigaciones Científicas; España Fil: Duffard, R.. Consejo Superior de Investigaciones Científicas; España Fil: Thirouin, A.. Consejo Superior de Investigaciones Científicas; España Fil: Castro-Tirado, A.J.. Consejo Superior de Investigaciones Científicas; España Fil: Jelínek, M.. Consejo Superior de Investigaciones Científicas; España Fil: Kubánek, P.. Consejo Superior de Investigaciones Científicas; España Fil: Sota, A.. Consejo Superior de Investigaciones Científicas; España Fil: Sánchez-Ramírez, R.. Consejo Superior de Investigaciones Científicas; España Fil: Andrei, A.H.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Universidade Federal do Rio de Janeiro; Brasil Fil: Camargo, J.I.B.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Universidade Federal do Rio de Janeiro; Brasil Fil: Da Silva Neto, D.N.. Centro Universitário Estadual Da Zona Oeste; . Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Gomes Jr., A. Ramos. Universidade Federal do Rio de Janeiro; Brasil Fil: Martins, R. Vieira. Universite Pierre et Marie Curie; Francia. Universidade Federal do Rio de Janeiro; Brasil. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Gillon, M.. Université de Liège; Bélgica Fil: Manfroid, J.. Université de Liège; Bélgica Fil: Tozzi, G.P.. Osservatorio Astrofisico di Arcetri; Italia Fil: Harlingten, C.. Caisey Harlingten Observatory; Reino Unido Fil: Saravia, S.. San Pedro de Atacama Celestial Explorations; Chile Fil: Behrend, R.. Universidad de Ginebra; Suiza Fil: Mottola, S.. German Aerospace Center; Alemania Fil: Melendo, E. García. Universitat Autònoma de Barcelona; España. Consejo Superior de Investigaciones Científicas; España Fil: Peris, V.. Universidad de Valencia; España Fil: Fabregat, J.. Universidad de Valencia; España Fil: Madiedo, J.M.. Universidad de Huelva; España Fil: Cuesta, L.. Consejo Superior de Investigaciones Científicas; España Fil: Eibe, M.T.. Consejo Superior de Investigaciones Científicas; España Fil: Ullán, A.. Consejo Superior de Investigaciones Científicas; España Fil: Organero, F.. Observatorio astronómico de La Hita; España Fil: Pastor, S.. Observatorio de la Murta; España Fil: De Los Reyes, J.A.. Observatorio de la Murta; España Fil: Pedraz, S.. Centro Astronómico Hispano Alemán; España Fil: Castro, A.. Centro Cultural José María Gutiérrez Romero; España Fil: De La Cueva, I.. Astroimagen; España Fil: Muler, G.. Observatorio Nazaret; España Fil: Steele, I.A.. Liverpool JMU; Reino Unido Fil: Cebrián, M.. Instituto Astrofisico de Canarias; Fil: Montañés-Rodríguez, P.. Instituto Astrofisico de Canarias; España Fil: Oscoz, A.. Instituto Astrofisico de Canarias; España Fil: Weaver, D.. Observatório Astronomico Christus; Brasil Fil: Jacques, C.. Observatório CEAMIG-REA; Brasil Fil: Corradi, W.J.B.. Universidade Federal do Minas Gerais; Brasil Fil: Santos, F.P.. Universidade Federal do Minas Gerais; Brasil Fil: Reis, W.. Universidade Federal do Minas Gerais; Brasil Fil: Milone, A.. Instituto Nacional de Pesquisas Espaciais; Brasil Fil: Emilio, M.. Universidade Estadual de Ponta Grossa; Brasil Fil: Gutiérrez, L.. Universidad Nacional Autónoma de México; México Fil: Vázquez, R.. Universidad Nacional Autónoma de México; México Fil: Hernández Toledo, H.. Universidad Nacional Autónoma de México; México

The Sun is located inside an extremely low density region called the Local Bubble (LB). Although they have been studied through a large variety of techniques, the contours of its neutral boundary, defined by a dense wall of interstellar gas and dust, are still an open issue. Our aim is to determine the interstellar reddening in the LB region by means of Stromgren photometry, validating the conclusions through a comparison with high-resolution three-dimensional (3D) hydrodynamical models of the Local and Loop I bubbles' formation and evolution. We have obtained color excesses and distances using the uvbyHβ data of the General Catalogue of Photometric Data, complemented by 820 stars from more recent catalogs, for b ≤ 60°. A set of restrictive exclusion criteria has been applied to eliminate E(b – y) values inappropriate for the study of the interstellar medium (ISM). The final sample has 8492 stars located up to 500 pc from the Sun. Our main results are as follows: (1) the large-scale distribution of the interstellar dust in the LB is highly inhomogeneous; (2) on the Galactic plane, E(b – y) ≥ 0040 is observed at a distance of d ≈ 80-100 pc from l ≥ 270° until l ≤ 45°; (3) the color excess suggests that there are many tunnels and holes in the LB wall; and (4) there is a clear correlation between E(b – y) and the spatial density distribution of the interstellar gas inferred from the simulations.

The Sun is located inside an extremely low density and quite irregular volume of the interstellar medium, known as the Local Cavity (LC). It has been widely believed that some kind of interaction could be occurring between the LC and Loop I, a nearby superbubble seen in the direction of the Galactic Center. As a result of such interaction, a wall of neutral and dense material, surrounded by a ring shaped feature, would be formed at the interaction zone. Evidence of this structure was previously observed by analyzing the soft X-ray emission in the direction of Loop I. Our goal is to investigate the distance of the proposed annular region and map the geometry of the Galactic magnetic field in these directions. On that account, we have conducted an optical polarization survey to 878 stars from the Hipparcos catalogue. Our results suggest that the structure is highly twisted and fragmented, showing very discrepant distances along the annular region: approximately 100 pc to the left side and 250 pc to the right side, independently confirming the indication from a previous photometric analysis. In addition, the polarization vectors' orientation pattern along the ring also shows a widely different behavior toward both sides of the studied feature, running parallel to the ring contour in the left side and showing no relation to its direction in the right side. Altogether, these evidence suggest a highly irregular nature, casting some doubt on the existence of a unique large-scale ring-like structure., Comment: 33 pages, 7 figures, accepted for publication at The Astrophysical Journal

Introduction: The treatment of human hematologic malignancies has rapidly advanced through the application of genomic platforms that have identified drug-able targets and companion diagnostics (e.g. BCR-ABL, IDH-1) and added new classes of targeted agents to the established compendium of cytotoxics. Despite these advances, the complexity, redundancy and promiscuity of cellular transformation remain incompletely understood at the molecular level. This has led to a renewed interest in whole cell experimental models for drug discovery. Laboratory platforms that measure cellular response to cytotoxic insult at the phenotypic level have been shown to correlate significantly with clinical response, and have the capacity to provide insights into chemotherapy selection and drug development. The Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) uses metabolic and morphologic features of drug induced cell death to measure both cytotoxic and targeted drug effects in human primary cultures. We applied EVA/PCD in 20 heavily pre-treated, drug refractory patients from the Hospital Israelita Albert Einstein (HIAE) in Sao Paulo - Brazil. Methods: Peripheral blood, node biopsy or bone marrow aspirates were submitted by overnight courier. Cells isolated by density centrifugation were evaluated by dose response curves that were interpolated to provide LC50 values for comparison with our databases by Z-score. Patients with Acute Lymphoblastic Leukemia (ALL, N=5) , Acute Myeloid Leukemia (AML, N=6), Non-Hodgkin Lymphoma (NHL, N=4) or Multiple Myeloma (MM, N=4) had received a mean of 5, median of 4 (range 1-8) prior therapies, 7 with prior bone marrow transplantation (BMT). Results: of 20 specimens, 16 (80%) provided viable tumor for EVA/PCD. A mean of 8, median of 7(range 3-22) cytotoxics and a mean 7, median of 5(range 1-20) targeted agents were evaluated. Findings were reported by day 7. Nine of 16 patients were treatment candidates, with 5 lost to follow up, 3 dying of sepsis before evaluation and 1 achieving complete remission (CR) with radiation plus Rituximab. Of 7 patients who received assay directed therapy there were 3 CR (43%), 2 partial responses (PR: 28%) and 2 progressive disease (PD: 29%) for an overall response rate of 71%. Conclusion: These results establish the feasibility of laboratory directed therapy in heavily pre-treated patients, with 80% of submitted samples providing actionable results. Although the extremely advanced state of these patients limited the capacity to undergo treatment in some cases, the achievement of CR's and PR's in this drug refractory cohort is of interest. Clinical responses by disease, treatment history and drugs received will be reported. Studies correlating molecular profiles with phenotypic analyses are currently under development. Disclosures Evans: Rational Therapeutics: Employment. Nagourney:Rational Therapeutics: Employment.