Myeloid-derived Suppressor Cells in Glioblastoma Patients - Phenotype, Function and Clinical Relevance

Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of myeloid cells that are significantly expanded in cancer patients and are associated with tumor progression. Multicolor flow cytometry was used to study the frequency, phenotype, and function of MDSCs in peripheral blood and freshly resected tumors of 52 participants with primary glioblastoma (GBM). This thesis provides a detailed characterization of different MDSC subsets in GBM patients and indicate that both granulocytic MDSCs in peripheral blood and at the tumor site play a major role in GBM-induced T-cell suppression

Recurrence of chronic subdural hematoma due to low-grade infection

Despite the high incidence and multitudes of operative techniques, the risk factors for chronic subdural hematoma (CSDH) recurrence are still under debate and a universal consensus on the pathophysiology is lacking. We hypothesized that clinically inapparent, a low-grade infection could be responsible for CSDH recurrence. This investigation is a single-center prospective observational study including patients with recurrent CSDH. In total, 44 patients with CSDH recurrence received an intraoperative swab-based microbiological test. The intraoperative swab revealed an inapparent low-grade hematoma infection in 29% of the recurrent CSDH cases. The majority (69%) of the identified germs belonged to the staphylococcus genus. We therefore, propose a novel potential pathophysiology for CSDH recurrence

Influence of baryons on the orbital structure of dark matter haloes

We explore the dynamical signatures imprinted by baryons on dark matter haloes during the formation process using the OverWhelmingly Large Simulations (OWLS), a set of state-of-the-art high-resolution cosmological hydrodynamical simulations. We present a detailed study of the effects of the implemented feedback prescriptions on the orbits of dark matter particles, stellar particles and subhaloes, analysing runs with no feedback, with stellar feedback and with feedback from supermassive black holes. We focus on the central regions (0.25 r_{200}) of haloes with virial masses ~ 6 x 10^{13} (~ 7 x 10^{11}) Msun/h at z = 0(2). We also investigate how the orbital content (relative fractions of the different orbital types) of these haloes depends on several key parameters such as their mass, redshift and dynamical state. The results of spectral analyses of the orbital content of these simulations are compared, and the change in fraction of box, tube and irregular orbits is quantified. Box orbits are found to dominate the orbital structure of dark matter haloes in cosmological simulations. There is a strong anticorrelation between the fraction of box orbits and the central baryon fraction. While radiative cooling acts to reduce the fraction of box orbits, strong feedback implementations result in a similar orbital distribution to that of the dark matter only case. The orbital content described by the stellar particles is found to be remarkably similar to that drawn from the orbits of dark matter particles, suggesting that either they have forgotten their dynamical history, or that subhaloes bringing in stars are not biased significantly with respect to the main distribution. The orbital content of the subhaloes is in broad agreement with that seen in the outer regions of the particle distributions.Comment: 18 pages, 13 figures, 3 tables. Accepted for publication in MNRA

Ongoing Assembly of Massive Galaxies by Major Merging in Large Groups and Clusters from the SDSS

We investigate the incidence of major mergers creating >10e11 Msun galaxies in present-day groups and clusters more massive than 2.5e13 Msun. We identify 38 pairs of massive galaxies with mutual tidal interaction signatures selected from >5000 galaxies with >5e10 Msun that reside in 845 such groups. We fit the images of each galaxy pair as the line-of-sight projection of symmetric models and identify mergers by the presence of residual asymmetries around each progenitor, such as off-center isophotes, broad tidal tails, and dynamical friction wakes. At the resolution and sensitivity of the SDSS, such mergers are found in 16% of high-mass, galaxy-galaxy pairs with magnitude differences of <1.5 and <30 kpc projected separations. We find that 90% of these mergers have nearly equal-mass progenitors with red-sequence colors and centrally-concentrated morphologies, the hallmarks of dissipationless merger simulations. Mergers at group centers are more common than between 2 satellites, but both are morphologically indistinguishable and we tentatively conclude that the latter are likely located at the dynamical centers of recently accreted subhalos. The frequency of central and satellite merging diminishes with group mass consistent with dynamical friction expectations. Based on reasonable assumptions, the centers of these massive halos are growing in stellar mass by 1-9% per Gyr, on average. Compared to all LRG-LRG mergers, we find a 2-9 times higher rate for their merging when restricted to these dense environments. Our results imply that the massive end of the galaxy population continues to evolve hierarchically at a measurable level, and that the centers of massive groups are the preferred environment for merger-driven galaxy assembly. (abridged)Comment: 48 pages, 21 figures. Submitted for publication in MNRAS. Version with full resolution figures at http://www.astro.umass.edu/~dmac/Preprints/mergers.hires.pd

Frailty in cerebellar ischemic stroke—The significance of temporal muscle thickness

While comprising only 2% of all ischemic strokes, cerebellar strokes are responsible for substantial morbidity and mortality due to their subtle initial presentation and the morbidity of posterior fossa swelling. Furthermore, low temporal muscle thickness (TMT) has recently been identified as a prognostic imaging parameter to assess patient frailty and outcome. We analyzed radiological and clinical data sets of 282 patients with cerebellar ischemic stroke. Our analysis showed a significant association between low TMT, reduced NIHSS and mRS at discharge (p = 0.035, p = 0.004), and reduced mRS at 12 months (p = 0.001). TMT may be used as a prognostic imaging marker and objective tool to assess outcomes in patients with cerebellar ischemic stroke

Barred Galaxies in the Abell 901/2 Supercluster with STAGES

We present a study of bar and host disk evolution in a dense cluster environment, based on a sample of ~800 bright (MV <= -18) galaxies in the Abell 901/2 supercluster at z~0.165. We use HST ACS F606W imaging from the STAGES survey, and data from Spitzer, XMM-Newton, and COMBO-17. We identify and characterize bars through ellipse-fitting, and other morphological features through visual classification. (1) We explore three commonly used methods for selecting disk galaxies. We find 625, 485, and 353 disk galaxies, respectively, via visual classification, a single component S'ersic cut (n <= 2.5), and a blue-cloud cut. In cluster environments, the latter two methods miss 31% and 51%, respectively, of visually-identified disks. (2) For moderately inclined disks, the three methods of disk selection yield a similar global optical bar fraction (f_bar-opt) of 34% +10%/-3%, 31% +10%/-3%, and 30% +10%/-3%, respectively. (3) f_bar-opt rises in brighter galaxies and those which appear to have no significant bulge component. Within a given absolute magnitude bin, f_bar-opt is higher in visually-selected disk galaxies that have no bulge as opposed to those with bulges. For a given morphological class, f_bar-opt rises at higher luminosities. (4) For bright early-types, as well as faint late-type systems with no evident bulge, the optical bar fraction in the Abell 901/2 clusters is comparable within a factor of 1.1 to 1.4 to that of field galaxies at lower redshifts (5) Between the core and the virial radius of the cluster at intermediate environmental densities, the optical bar fraction does not appear to depend strongly on the local environment density and varies at most by a factor of ~1.3. We discuss the implications of our results for the evolution of bars and disks in dense environments.Comment: accepted for publication in ApJ, abstract abridged, for high resolution figures see http://www.as.utexas.edu/~marinova/STAGES/STAGES_bars.pd

Haloes gone MAD: The Halo-Finder Comparison Project

[abridged] We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including friends-of-friends (FOF), spherical-overdensity (SO) and phase-space based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allows halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large-scale structure of the universe. All the halo finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Via a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30-40 particles. However, also here the phase space finders excelled by resolving substructure down to 10-20 particles. By comparing the halo finders using a high resolution cosmological volume we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity, and peak of the rotation curve).Comment: 27 interesting pages, 20 beautiful figures, and 4 informative tables accepted for publication in MNRAS. The high-resolution version of the paper as well as all the test cases and analysis can be found at the web site http://popia.ft.uam.es/HaloesGoingMA

A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases

BackgroundThe differentiation of high-grade glioma and brain tumors of an extracranial origin is eminent for the decision on subsequent treatment regimens. While in high-grade glioma, a surgical resection of the tumor mass is a fundamental part of current standard regimens, in brain metastasis, the burden of the primary tumor must be considered. However, without a cancer history, the differentiation remains challenging in the imaging. Hence, biopsies are common that may help to identify the tumor origin. An additional tool to support the differentiation may be of great help. For this purpose, we aimed to identify a biomarker panel based on the expression analysis of a small sample of tissue to support the pathological analysis of surgery resection specimens. Given that an aberrant glutamate signaling was identified to drive glioblastoma progression, we focused on glutamate receptors and key players of glutamate homeostasis.MethodsBased on surgically resected samples from 55 brain tumors, the expression of ionotropic and metabotropic glutamate receptors and key players of glutamate homeostasis were analyzed by RT-PCR. Subsequently, a receiver operating characteristic (ROC) analysis was performed to identify genes whose expression levels may be associated with either glioblastoma or brain metastasis.ResultsOut of a total of 29 glutamatergic genes analyzed, nine genes presented a significantly different expression level between high-grade gliomas and brain metastases. Of those, seven were identified as potential biomarker candidates including genes encoding for AMPA receptors GRIA1, GRIA2, kainate receptors GRIK1 and GRIK4, metabotropic receptor GRM3, transaminase BCAT1 and the glutamine synthetase (encoded by GLUL). Overall, the biomarker panel achieved an accuracy of 88% (95% CI: 87.1, 90.8) in predicting the tumor entity. Gene expression data, however, could not discriminate between patients with seizures from those without.ConclusionWe have identified a panel of seven genes whose expression may serve as a biomarker panel to discriminate glioblastomas and brain metastases at the molecular level. After further validation, our biomarker signatures could be of great use in the decision making on subsequent treatment regimens after diagnosis

Halo Shapes From Weak Lensing: The Impact of Galaxy--Halo Misalignment

We analyse the impact of galaxy--halo misalignment on the ability of weak lensing studies to constrain the shape of dark matter haloes, using a combination of the Millennium dark matter N-body simulation and different semi-analytic galaxy formation models, as well as simpler Monte Carlo tests. Since the distribution of galaxy--halo alignments is not known in detail, we test various alignment models, together with different methods of determining the halo shape. In addition to alignment, we examine the interplay of halo mass and shape, and galaxy colour and morphology with the resulting stacked projected halo shape. We find that only in the case where significant numbers of galaxy and halo minor axes are parallel does the stacked, projected halo axis ratio fall below 0.95. When using broader misalignment distributions, such as those found in recent simulations of galaxy formation, the halo ellipticity signal is washed out and would be extremely difficult to measure observationally. It is important to note that the spread in stacked halo axis ratio due to theoretical unknowns (differences between semi-analytic models, and between alignment models) are much bigger than any statistical uncertainty: It is naive to assume that, simply because LCDM predicts aspherical haloes, the stacked projected shape will be elliptical. In fact, there is no robust LCDM prediction yet for this procedure, and the interpretation of any such elliptical halo signal from lensing in terms of physical halo properties will be extremely difficult.Comment: 22 pages, 19 figures, accepted for publication in MNRAS. Minor changes for clarification and correcting typeo

Dexamethasone treatment limits efficacy of radiation, but does not interfere with glioma cell death induced by tumor treating fields

Purpose: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive. Methods: Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/- concomitant Dex and analysed its impact on progression-free (PFS) and overall survival (OS). Results: The addition of Dex significantly reduced the efficacy of RT in U251, but not in MZ54 cells. TTFields (200 kHz/250 kHz) induced massive cell death in both cell lines. Concomitant treatment of TTFields and Dex did not reduce the overall efficacy of TTFields. Further, in our retrospective clinical analysis, we found that the addition of Dex to TTFields therapy did not influence PFS nor OS. Conclusion: Our translational investigation indicates that the efficacy of TTFields therapy in patients with GBM and GBM cell lines is not affected by the addition of Dex