53 research outputs found

    Soluble triggering receptor expressed on myeloid cells 1 in lung cancer

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    Soluble Triggering Receptor Expressed on Myeloid Cells 1 (sTREM-1) can be found in the sera of patients with infectious, autoimmune and malignant diseases. The primary objective of this study was to investigate the prognostic significance of sTREM-1 in lung cancer patients. We analyzed the sera of 164 patients with lung cancer of all histologies and all stages at the time of diagnosis. We employed an ELISA using the anti-TREM-1 clone 6B1.1G12 mAb and recombinant human TREM-1. Patient data was collected retrospectively by chart review. In ROC-analysis, a sTREM-1 serum level of 163.1  pg/ml showed the highest Youden-Index. At this cut-off value sTREM-1 was a marker of short survival in patients with NSCLC (median survival 8.5 vs. 13.3 months, p = 0.04). A Cox regression model showed stage (p < 0.001) and sTREM-1 (p = 0.011) to indicate short survival. There were no differences in sTREM-1 serum values among patients with or without infection, pleural effusion or COPD. sTREM-1 was not associated with metastasis at the time of diagnosis and was not a predictor of subsequent metastasis. In SCLC patients sTREM-1 levels were lower than in NSCLC patients (p = 0.001) and did not predict survival. sTREM-1 did not correlate with CRP or the number of neutrophils. In non-small cell lung cancer patients, sTREM-1 in serum has prognostic significance

    Metallicities of Emission-Line Galaxies from HST ACS PEARS and HST WFC3 ERS Grism Spectroscopy at 0.6 is less than z is less than 2.4

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    Galaxies selected on the basis of their emission line strength. show low metallicities, regardless of their redshifts. We conclude this from a sample of faint galaxies at redshifts between 0.6 < z < 2.4, selected by their prominent emission lines in low resolution grism spectra in the optiCa.i with the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope (HST) and in the near-infrared using Wide-Field Camera 3 (WFC3). Using a sample of 11 emission line galaxies (ELGs) at 0.6 < z < 2.4 with luminosities of -22 approx < MB approx -19 which have [OII], H-Beta, and [OIII] line flux measurements from the combination of two grism spectral surveys, we use the R23 method to derive the gas-phase oxygen abundances: 7.5 <12+log(0/H)<8.5. The galaxy stellar masses are derived using Bayesian based Markov Chain Monte Carlo (pi MC(exp 2)) fitting of their Spectral Energy Distribution (SED), and span the mass range 8.1 < log(M(stellar)/M(solar)) < 10.1. These galaxies show a mass-metal1icity (M-L) and Luminosity-Metallicity (LZ) relation, which is offset by -<J.6 dex in meta1licity at given absolute magnitude and stellar mass relative to the local SDSS galaxies, as well as continuum selected DEEP2 samples at similar redshifts. The emission-line selected galaxies most resemble the local "green peas" galaxies and Lyman-alpha galaxies at z approx = 0.3 and z approx = 2.3 in the M-Z and L-Z relations and their morphologies. The G - M(sub 20) morphology analysis shows that 10 out of 11 show disturbed morphology, even as the star-forming regions are compact. These galaxies may be intrinsically metal poor, being at early stages of formation, or the low metallicities may be due to gas infall and accretion due to mergers

    The WFC3 Infrared Spectroscopic Parallel (WISP) Survey

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    We present the WFC3 Infrared Spectroscopic Parallel (WISP) Survey. WISP is obtaining slitless, near-infrared grism spectroscopy of ~ 90 independent, high-latitude fields by observing in the pure parallel mode with Wide Field Camera-3 on the Hubble Space Telescope for a total of ~ 250 orbits. Spectra are obtained with the G102 (lambda=0.8-1.17 microns, R ~ 210) and G141 grisms (lambda=1.11-1.67 microns, R ~ 130), together with direct imaging in the J- and H-bands (F110W and F140W, respectively). In the present paper, we present the first results from 19 WISP fields, covering approximately 63 square arc minutes. For typical exposure times (~ 6400 sec in G102 and ~ 2700 sec in G141), we reach 5-sigma detection limits for emission lines of 5 x 10^(-17) ergs s^(-1) cm^(-2) for compact objects. Typical direct imaging 5sigma-limits are 26.8 and 25.0 magnitudes (AB) in F110W and F140W, respectively. Restricting ourselves to the lines measured with highest confidence, we present a list of 328 emission lines, in 229 objects, in a redshift range 0.3 < z < 3. The single-line emitters are likely to be a mix of Halpha and [OIII]5007,4959 A, with Halpha predominating. The overall surface density of high-confidence emission-line objects in our sample is approximately 4 per arcmin^(2).These first fields show high equivalent width sources, AGN, and post starburst galaxies. The median observed star formation rate of our Halpha selected sample is 4 Msol/year. At intermediate redshifts, we detect emission lines in galaxies as faint as H_140 ~ 25, or M_R < -19, and are sensitive to star formation rates down to less than 1 Msol/year. The slitless grisms on WFC3 provide a unique opportunity to study the spectral properties of galaxies much fainter than L* at the peak of the galaxy assembly epoch.Comment: 15 pages, 12 figures, submitted to Ap

    Uncertainties and controversies in axillary management of patients with breast cancer

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    The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register

    Galaxies Going Bananas: Inferring the 3D Geometry of High-Redshift Galaxies with JWST-CEERS

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    The 3D geometry of high-redshift galaxies remains poorly understood. We build a differentiable Bayesian model and use Hamiltonian Monte Carlo to efficiently and robustly infer the 3D shapes of star-forming galaxies in JWST-CEERS observations with logM/M=9.010.5\log M_*/M_{\odot}=9.0-10.5 at z=0.58.0z=0.5-8.0. We reproduce previous results from HST-CANDELS in a fraction of the computing time and constrain the mean ellipticity, triaxiality, size and covariances with samples as small as 50\sim50 galaxies. We find high 3D ellipticities for all mass-redshift bins suggesting oblate (disky) or prolate (elongated) geometries. We break that degeneracy by constraining the mean triaxiality to be 1\sim1 for logM/M=9.09.5\log M_*/M_{\odot}=9.0-9.5 dwarfs at z>1z>1 (favoring the prolate scenario), with significantly lower triaxialities for higher masses and lower redshifts indicating the emergence of disks. The prolate population traces out a ``banana'' in the projected b/alogab/a-\log a diagram with an excess of low b/ab/a, large loga\log a galaxies. The dwarf prolate fraction rises from 25%\sim25\% at z=0.51.0z=0.5-1.0 to 5080%\sim50-80\% at z=38z=3-8. If these are disks, they cannot be axisymmetric but instead must be unusually oval (triaxial) unlike local circular disks. We simultaneously constrain the 3D size-mass relation and its dependence on 3D geometry. High-probability prolate and oblate candidates show remarkably similar S\'ersic indices (n1n\sim1), non-parametric morphological properties and specific star formation rates. Both tend to be visually classified as disks or irregular but edge-on oblate candidates show more dust attenuation. We discuss selection effects, follow-up prospects and theoretical implications.Comment: Submitted to ApJ, main body is 35 pages of which ~half are full-page figures, comments welcom

    Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

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    Aim: Demand for nipple-and skin-sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recom-mendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BRPeer reviewe

    Comparison of multivariate data analysis strategies for high-content screening

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    High content screening (HCS) is increasingly used in biomedical research generating multivariate, single-cell datasets. Before scoring a treatment the complex datasets are processed (e.g. normalized, reduced to a lower dimensionality) to help extracting valuable information. However, there has been no published comparison of the performance of these methods. This study comparatively evaluates unbiased approaches to reduce dimensionality as well as to summarize cell populations. To evaluate these different data processing strategies the prediction accuracies and the Z’ factors of control compounds of a HCS cell cycle dataset were monitored. As expected dimension reduction leads to a lower degree of discrimination between control samples. A high degree of classification accuracy was achieved when the cell population was summarized on well level using percentile values. As a conclusion, the generic data analysis pipeline described here enables a systematic review of alternative strategies to analyze multiparametric results from biological systems

    ERBB2 mutation is associated with sustained tumor cell proliferation after short-term preoperative endocrine therapy in early lobular breast cancer

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    Invasive lobular breast cancer (ILC) is a special breast cancer (BC) subtype and is mostly hormone receptor (HR)-positive and ERBB2 non-amplified. Endocrine therapy restrains tumor proliferation and is the mainstay of lobular BC treatment. Mutation of ERBB2 has been associated with recurrent ILC. However, it is unknown whether ERBB2 mutation impacts on the otherwise exquisite responsiveness of early ILC to endocrine therapy. We have recently profiled n = 622 HR-positive early BCs from the ADAPT trial for mutations in candidate genes involved in endocrine resistance, including ERBB2. All patients were treated with short-term preoperative endocrine therapy (pET, tamoxifen or aromatase inhibitors) before tumor resection. Tumor proliferation after endocrine therapy (post-pET Ki67 index) was determined prospectively by standardized central pathology assessment supported by computer-assisted image analysis. Sustained or suppressed proliferation were defined as post-pET Ki67 =10% or <10%. Here, we report a subgroup analysis pertaining to ILCs in this cohort. ILCs accounted for 179/622 (28.8%) cases. ILCs were enriched in mutations in CDH1 (124/179, 69.3%, P < 0.0001) and ERBB2 (14/179, 7.8%, P < 0.0001), but showed fewer mutations in TP53 (7/179, 3.9%, P = 0.0048) and GATA3 (11/179, 6.1%, P < 0.0001). Considering all BCs irrespective of subtypes, ERBB2 mutation was not associated with proliferation. In ILCs, however, ERBB2 mutations were 3.5-fold more common in cases with sustained post-pET proliferation compared to cases with suppressed post-pET proliferation (10/75, 13.3% versus 4/104, 3.8%, P = 0.0248). Moreover, ERBB2 mutation was associated with high Oncotype DX recurrence scores (P = 0.0087). In summary, our findings support that ERBB2 mutation influences endocrine responsiveness in early lobular BC

    Euclid SGS MER Processing Function Requirements Specification Document

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    Version 0.9 reviewed by ESA at the Euclid SGS System Requirements Review (2015) Version 0.97 provided as reference document for the ESA Euclid SGS Design Review (2017) Version 1.0 provided as reference document for the ESA Euclid SGS Implementation Review (2021)The MER Processing Function realises the merging of all the level 2 information and provides source catalogues containing object information relevant in the Euclid project. It starts from level 2 data provided by related OUs (VIS/NIR/EXT stacks or single epoch images, related PSF models and ancillary information); an object detection is performed in VIS and NIR, and the detected objects are combined. A multi-wavelength flux determination is performed on detected objects with suitable photometric techniques. The final output of the MER processing function is a catalogue of sources with unique identification number and multi-wavelength photometric information; the MER PF will also provide the required input (object identification number, position, fluxes, galactic extinction, effective wavelength of EXT passbands at objects’ positions) for photometric redshifts computation and spectra extraction. The Euclid SGS requirements specification produces the Euclid SGS Requirements Specification Document and a set of Requirements Specification Documents for specific SGS products such as the Processing Functions. The present document is part of this set. To ensure completeness and consistency with applicable documents, traceability and verification matrices complement the SGS Requirements Specification Documents
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