Purveyors of fine halos: Re-assessing globular cluster contributions to the Milky Way halo build-up with SDSS-IV

There is ample evidence in the Milky Way for globular cluster (GC) disruption. Hence one may expect that also part of the Galactic halo field stars may once have formed in GCs. We quantify the fraction of halo stars donated by GCs by searching for stars that bear the unique chemical fingerprints typical for a subset of GC stars often dubbed `second-generation stars'. These are stars showing light element abundance anomalies such as a pronounced CN-band strength accompanied by weak CH-bands. Based on this indicator, past studies have placed the fraction of halo stars with a GC origin between a few to up to 50%. Using low-resolution spectra from the most recent data release of the latest extension of the Sloan Digital Sky Survey (SDSS-IV), we were able to identify 118 metal-poor ($-1.8\le$[Fe/H]$\le -1.3$) CN-strong stars in a sample of 4470 halo giant stars out to 50 kpc. This results in an observed fraction of these stars of 2.6$\pm$0.2%. Using an updated formalism to account for the fraction of stars lost early on in the GCs' evolution we estimate the fraction of the halo that stems from disrupted clusters to be 11$\pm$1%. This number represents the case that stars lost from GCs were entirely from the first generation and is thus merely an upper limit. Our conclusions are sensitive to our assumptions of the mass lost early on from the first generation formed in the GCs, the ratio of first-to-second generation stars, and other GC parameters. We carefully test the influence of varying these parameters on the final result and find that, under realistic scenarios, the above fraction depends on the main assumptions at less than 10%. We further recover a flat trend in this fraction with Galactocentric radius, with a marginal indication of a rise beyond 30 kpc that could reflect the ex-situ origin of the outer halo. (abridged)Comment: 13 pages, 11 figures, accepted for publication in Astronomy & Astrophysic

Supersensitive PSA-Monitored neoadjuvant hormone treatment of clinically localized prostate cancer: Effects on positive margins, tumor detection and epithelial cells in bone marrow

Objective: The present study was done to investigate the effects of supersensitive PSA-controlled inductive treatment on positive margins, detection of tumor and epithelial cells in bone marrow of 101 patients with untreated and clinically localized prostatic carcinoma (cT1-3N0M0). Methods: Hormonal treatment was given until PSA (DPD Immulite(R) third-generation assay) reached 0.3 ng/ml in only 1 case. Of the 101 patients, 82 had a measurable hypoic lesion on initial transrectal ultrasound. 84% of these became smaller, 7.5% remained unchanged and 8.5% increased. Of the 101 prostatectomy specimens, 20 (20%) were margin-positive. The incidence of affected margins was relatively high (35% from 55 patients) with cT3 tumors, but almost negligible (2% from 46 patients) in cT1-2 tumor. Our pathologists, despite their great experience in evaluating hormonally treated prostates (>500 cases) and using immunohistochemical staining, were unable to detect carcinoma in 15 (15%) specimens. Whereas only 2 (4%) of the 55 cT3 specimens were without detectable tumor, this incidence rised to 28% (13 of 46 prostates) in patients with cT1-2 tumors. Of the initial 29 patients with epithelial cells in bone marrow, only 4 (14%) remained positive after controlled induction and all of them had fewer cells than before. Conclusion: Endocrine induction controlled by a supersensitive PSA assay and continued until reaching PSA nadir is highly effective in clearing surgical margins and eliminating tumor cells from bone marrow. It seems to be clearly superior to the conventional 3 months of pretreatment at least in cT1-2 tumors in respect to surgical margins and detectability of tumor in the resected prostate. A definitive statement about the value of endocrine induction can only be given by prospective randomized studies, with optimal drugs, doses and treatment time. But the conventional 3 months of pretreatment are far from exploiting the possibilities of this therapeutic option

Building the Galactic halo from globular clusters: evidence from chemically unusual red giants

We present a spectroscopic search for halo field stars that originally formed in globular clusters. Using moderate-resolution SDSS-III/SEGUE-2 spectra of 561 red giants with typical halo metallicities (-1.8 < [Fe/H] < -1.0), we identify 16 stars, 3% of the sample, with CN and CH bandstrength behavior indicating depleted carbon and enhanced nitrogen abundances relative to the rest of the data set. Since globular clusters are the only environment known in which stars form with this pattern of atypical light-element abundances, we claim that these stars are second-generation globular cluster stars that have been lost to the halo field via normal cluster mass-loss processes. Extrapolating from theoretical models of two-generation globular cluster formation, this result suggests that globular clusters contributed significant numbers of stars to the construction of the Galactic halo: we calculate that a minimum of 17% of the present-day mass of the stellar halo was originally formed in globular clusters. The ratio of CN-strong to CN-normal stars drops with Galactocentric distance, suggesting that the inner-halo population may be the primary repository of these stars.Comment: 9 pages including 8 figures, A&A accepte

hVH-5: A Protein Tyrosine Phosphatase Abundant in Brain that Inactivates Mitogen-Activated Protein Kinase

A novel protein tyrosine phosphatase [ h omologue of v accinia virus H 1 phosphatase gene clone 5 (hVH-5)] was cloned; it shared sequence similarity with a subset of protein tyrosine phosphatases that regulate mitogen-activated protein kinase. The catalytic region of hVH-5 was expressed as a fusion protein and was shown to hydrolyze p -nitrophenylphosphate and inactivate mitogen-activated protein kinase, thus proving that hVH-5 possessed phosphatase activity. A unique proline-rich region distinguished hVH-5 from other closely related protein tyrosine phosphatases. Another feature that distinguished hVH-5 from related phosphatases was that hVH-5 was expressed predominantly in the adult brain, heart, and skeletal muscle. In addition, in situ hybridization histochemistry of mouse embryo revealed high levels of expression and a wide distribution in the central and peripheral nervous system. Some specific areas of abundant hVH-5 expression included the olfactory bulb, retina, layers of the cerebral cortex, and cranial and spinal ganglia. hVH-5 was induced in PC12 cells upon nerve growth factor and insulin treatment in a manner characteristic of an immediate-early gene, suggesting a possible role in the signal transduction cascade.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65883/1/j.1471-4159.1995.65041823.x.pd

Antiretroviral therapy in a community clinic - early lessons from a pilot project

Objectives. To report on operational and clinical problems encountered during the first 6 months of a community-based antiretroviral therapy (ART) programme.Methods. ART was implemented in a primary care setting utilising an easily replicable service-delivery model based on a medical officer and nurse. Therapeutic counsellors, themselves HIV-infected, provided counselling and adherence support. Drug and monitoring costs were charitably funded and provincial health authorities supplied the medical infrastructure. The HIV Research Unit, University of Cape Town, supplied training and additional clinical support. Local HIV primary care clinics provided patient referrals. Standardised ART regimens were used with strict entry criteria (AIDS or CD4 count &lt; 200 cells/μl).                                                                    Results. Demand for the service was high. Referred patients had advanced disease (AIDS 57%, median CD4 count 96/μl) and high pre-treatment mortality (83/100 person-years). Mycobacterial disease was a major  contributor to this mortality (40%). Scheduled clinic visit hours were six times higher during recruitment than maintenance. Attributable costs were: drugs 61%, staff 2.7%, viral load and CD4 cell counts 10% and safety monitoring 2%. Viral load after 16 weeks of therapy was &lt; 400 copies/ml in the first 16 patients.Conclusions. ART can be successfully implemented within a primary care setting. Drug purchases and staff salaries drive programme costing. The service model is capable of managing 250 - 300 patients on chronic ART, but staffing needs to be increased during recruitment. Attention must be given to the diagnosis of tuberculosis during screening and early ART. Incorporating therapeutic counsellors into the programme increased community involvement and utilised a valuable and previously untapped resource

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

BACKGROUND:Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN:We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION:This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION:The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results

Chemical Doppelgangers in GALAH DR3: the Distinguishing Power of Neutron-Capture Elements Among Milky Way Disk Stars

The observed chemical diversity of Milky Way stars places important constraints on Galactic chemical evolution and the mixing processes that operate within the interstellar medium. Recent works have found that the chemical diversity of disk stars is low. For example, the APOGEE "chemical doppelganger rate," or the rate at which random pairs of field stars appear as chemically similar as stars born together, is high, and the chemical distributions of APOGEE stars in some Galactic populations are well-described by two-dimensional models. However, limited attention has been paid to the heavy elements (Z > 30) in this context. In this work, we probe the potential for neutron-capture elements to enhance the chemical diversity of stars by determining their effect on the chemical doppelganger rate. We measure the doppelganger rate in GALAH DR3, with abundances rederived using The Cannon, and find that considering the neutron-capture elements decreases the doppelganger rate from 2.2% to 0.4%, nearly a factor of 6, for stars with -0.1 < [Fe/H] < 0.1. While chemical similarity correlates with similarity in age and dynamics, including neutron-capture elements does not appear to select stars that are more similar in these characteristics. Our results highlight that the neutron-capture elements contain information that is distinct from that of the lighter elements and thus add at least one dimension to Milky Way abundance space. This work illustrates the importance of considering the neutron-capture elements when chemically characterizing stars and motivates ongoing work to improve their atomic data and measurements in spectroscopic surveys.Comment: 23 pages, 16 figures, 1 table. Submitted to AAS Journals, comments welcome. Associated catalog of high precision, Cannon-rederived abundances for GALAH giants to be made publicly available upon acceptance and available now upon request. See Walsen et al. 2023 for a complementary, high precision, Cannon-rederived abundance catalog for GALAH solar twin

Mass Segregation in the Globular Cluster Palomar 5 and its Tidal Tails

We present the stellar main sequence luminosity function (LF) of the disrupted, low-mass, low-concentration globular cluster Palomar 5 and its well-defined tidal tails, which emanate from the cluster as a result of its tidal interaction with the Milky Way. The results of our deep (B ~ 24.5) wide-field photometry unequivocally indicate that preferentially fainter stars were removed from the cluster so that the LF of the cluster's main body exhibits a significant degree of flattening compared to other globular clusters. There is clear evidence of mass segregation, which is reflected in a radial variation of the LFs. The LF of the tidal tails is distinctly enhanced with faint, low-mass stars. Pal 5 exhibits a binary main sequence, and we estimate a photometric binary frequency of roughly 10%. Also the binaries show evidence of mass segregation with more massive binary systems being more strongly concentrated toward the cluster center.Comment: 14 pages, 12 figures, accepted for publication in the Astronomical Journa

Medical Imaging Utilization Trends in Radiation Oncology over the Past Decade

Purpose/Objective(s): We quantify the increase in use of pre-treatment imaging and verification imaging in radiation oncology over the past decade. We also quantify the trend towards hypofractionation, which has partially led to increased imaging. Materials/Methods: The pre-treatment and verification imaging data used are from a single, tertiary, university-affiliated cancer center. Pre-treatment imaging was defined as magnetic resonance imaging (MRI), positron emission tomography (PET) and four-dimensional computed tomography (4DCT). Verification imaging was defined as cone-beam computed tomography (CBCT). All treatment approved plans were included from 2012 to 2021. Data extraction was performed using custom scripts interfacing with the treatment planning system (TPS) and patient information system. All registered image-sets of planning CT images with either advanced pre-treatment advanced imaging or verification images in the TPS were included. Hypofractionation sub-analysis was performed according to plans above and below 4 Gy per fraction that received a combination of pre-treatment and verification imaging. Results: Between 2012 and 2021, a total of 42,214 plans were included. In 2021, MRI, PET, and 4DCT pre-treatment imaging modalities were used for 14%, 5%, and 3% of patients, respectively, which was an increase from 5%, 2%, and 0%, in 2012. In 2021, 55% of patients received CBCT for verification imaging compared to only 2% of patients in 2012. In the sub-analysis, cohort receiving greater than or equal to 4 Gy per fraction from 2012 to 2021, the percent of patients receiving one of MRI or PET for pre-treatment imaging and CBCT guidance for verification imaging increased from 1% to 22%. For the cohort receiving less than 4 Gy per fraction, there was an increase from 2012 to 2021 of 0% to 14% of patients receiving at least one of MRI or PET pretreatment imaging and CBCT for verification imaging. Table 1: Annual use of advanced pre-treatment, verification imaging, hypofractionation, and associated combination imaging shown. Entries indicate the percent (%) of patients per year with the imaging modality used in their treatment. Conclusion: An increase in the adoption of advanced medical imaging was observed in standard of care treatments over the past 10 years. Imaging utilization continues to increase as clinical trial evidence matures. Further analysis could focus on the gap between desired standard of care for patients and the current offerings as well as the increase in capital and human resource requirement for implementation of these advancements