Observation of periodic variable stars towards the galactic spiral arms by EROS II

We present the results of a massive variability search based on a photometric survey of a six square degree region along the Galactic plane at ($l = 305^\circ$, $b = -0.8^\circ$) and ($l = 330^\circ$, $b = -2.5^\circ$). This survey was performed in the framework of the EROS II (Exp\'erience de Recherche d'Objets Sombres) microlensing program. The variable stars were found among 1,913,576 stars that were monitored between April and June 1998 in two passbands, with an average of 60 measurements. A new period-search technique is proposed which makes use of a statistical variable that characterizes the overall regularity of the flux versus phase diagram. This method is well suited when the photometric data are unevenly distributed in time, as is our case. 1,362 objects whose luminosity varies were selected. Among them we identified 9 Cepheids, 19 RR Lyrae, 34 Miras, 176 eclipsing binaries and 266 Semi-Regular stars. Most of them are newly identified objects. The cross-identification with known catalogues has been performed. The mean distance of the RR Lyrae is estimated to be $\sim 4.9 \pm 0.3$ kpc undergoing an average absorption of $\sim 3.4 \pm 0.2$ magnitudes. This distance is in good agreement with the one of disc stars which contribute to the microlensing source star population.Our catalogue and light curves are available electronically from the CDS, Strasbourg and from our Web site http://eros.in2p3.fr.Comment: 15 pages, 11 figures, accepted in A&A (april 2002

61MO Biomarker analysis of men with enzalutamide (enza)-resistant metastatic castration-resistant prostate cancer (mCRPC) treated with pembrolizumab (pembro) + enza in KEYNOTE-199

Background: In KEYNOTE-199 (NCT02787005), pembro + enza had durable antitumor activity in enza-refractory mCRPC. We evaluated the association between prespecified biomarkers and clinical outcomes. Methods: Cohorts 4 (C4; RECIST-measurable disease) and 5 (C5; nonmeasurable, bone-predominant disease) enrolled men with chemotherapy-naive mCRPC, irrespective of PD-L1 status, that progressed after initial response to enza. We evaluated TMB by whole exome sequencing (n = 64), PD-L1 combined positive score (CPS) by IHC (n = 124), and 18-gene T-cell–inflamed gene expression profile (TcellinfGEP) by NanoString (n = 51). Outcomes were DCR, PFS, PSA response, PSA progression, OS, and ORR per blinded independent review (C4 only). Significance of continuous biomarkers (CPS, TMB, GEP) was prespecified at 0.05 for 1-sided P values from logistic (ORR, DCR, PSA response) and Cox proportional hazard (PFS, OS, PSA progression) regression adjusted for ECOG PS. Results: In C4, ORR was 10% (5/48) in pts with evaluable TMB data and 12% (10/81) in pts with CPS data. In C4 and C5, 16% (10/64) and 14% (17/124) of pts with TMB and CPS data, respectively, achieved a PSA response. TMB was significantly associated with DCR (P = 0.03) and trended toward an association with PSA response (P = 0.08). TMB (AUROC [95% CI]: 0.68 [0.51-0.86]), but not CPS (0.54 [0.41-0.67]) or TcellinfGEP (0.55 [0.37-0.74]), enriched for PSA response. TMB (P = 0.04), but not CPS (P = 0.57) or TcellinfGEP (P = 0.32), was significantly associated with PSA progression. There was 1 MSI-H pt (per Promega PCR assay); this pt achieved an objective and PSA response and had PFS \u3e6 months. TMB, CPS, and TcellinfGEP were not associated with PFS or OS. There was a low prevalence of TMB ≥175 mut/exome (11%) and TcellinfGEP-high (≥−0.318; 16%). Conclusions: In this biomarker analysis of KEYNOTE-199 C4-C5, PD-L1 CPS and TcellinfGEP were not significantly associated with clinical outcome. Despite the low prevalence of TMB ≥175 mut/exome, TMB was positively associated with outcomes of pembro + enza in pts with mCRPC. The sample sizes for the exploratory analyses were small, and results should be interpreted with caution

Removing the Microlensing Blending-Parallax Degeneracy Using Source Variability

Microlensing event MACHO 97-SMC-1 is one of the rare microlensing events for which the source is a variable star, simply because most variable stars are systematically eliminated from microlensing studies. Using observational data for this event, we show that the intrinsic variability of a microlensed star is a powerful tool to constrain the nature of the lens by breaking the degeneracy between the microlens parallax and the blended light. We also present a statistical test for discriminating the location of the lens based on the \chi^2 contours of the vector \Lambda, the inverse of the projected velocity. We find that while SMC self lensing is somewhat favored over halo lensing, neither location can be ruled out with good confidence.Comment: 15 text pages + 2 tables + 7 figures. Published in the Astrophysical Journa

The Role of Dwarf Galaxy Interactions in Shaping the Magellanic System and Implications for Magellanic Irregulars

We present a novel pair of numerical models of the interaction history between the Large and Small Magellanic Clouds (LMC and SMC, respectively) and our Milky Way (MW) in light of recent high precision proper motions (Kallivayalil et al. 2006a,b). Given the new velocities, cosmological simulations of structure formation favor a scenario where the Magellanic Clouds (MCs) are currently on their first infall towards our Galaxy (Boylan-Kolchin et al. 2011, Busha et al. 2011). We illustrate here that the observed irregular morphology and internal kinematics of the MCs (in gas and stars) are naturally explained by interactions between the LMC and SMC, rather than gravitational interactions with the MW. This picture further supports a first infall scenario (Besla et a. 2007). In particular, we demonstrate that the Magellanic Stream, a band of HI gas trailing behind the MCs 150 degrees across the sky, can be accounted for by the action of LMC tides on the SMC before the system was accreted by the MW. We further demonstrate that the off-center, warped stellar bar of the LMC and its one-armed spiral, can be naturally explained by a recent direct collision with the SMC. Such structures are key morphological characteristics of a class of galaxies referred to as Magellanic Irregulars (de Vaucouleurs & Freeman 1972), the majority of which are not associated with massive spiral galaxies. We infer that dwarf-dwarf galaxy interactions are important drivers for the morphological evolution of Magellanic Irregulars and can dramatically affect the efficiency of baryon removal from dwarf galaxies via the formation of extended tidal bridges and tails. Such interactions are important not only for the evolution of dwarf galaxies but also have direct consequences for the buildup of baryons in our own MW, as LMC-mass systems are believed to be the dominant building blocks of MW-type halos.Comment: 33 pages, 21 figures, Accepted for publication in MNRAS, Dec 23 201

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

PKS 1502+106: a new and distant gamma-ray blazar in outburst discovered by the Fermi Large Area Telescope

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope discovered a rapid (about 5 days duration), high-energy (E >100 MeV) gamma-ray outburst from a source identified with the blazar PKS 1502+106 (OR 103, S3 1502+10, z=1.839) starting on August 05, 2008 and followed by bright and variable flux over the next few months. Results on the gamma-ray localization and identification, as well as spectral and temporal behavior during the first months of the Fermi all-sky survey are reported here in conjunction with a multi-waveband characterization as a result of one of the first Fermi multi-frequency campaigns. The campaign included a Swift ToO (followed up by 16-day observations on August 07-22, MJD 54685-54700), VLBA (within the MOJAVE program), Owens Valley (OVRO) 40m, Effelsberg-100m, Metsahovi-14m, RATAN-600 and Kanata-Hiroshima radio/optical observations. Results from the analysis of archival observations by INTEGRAL, XMM-Newton and Spitzer space telescopes are reported for a more complete picture of this new gamma-ray blazar.Comment: 17 pages, 11 figures, accepted for The Astrophysical Journa

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Combined Analysis of the Binary-Lens Caustic-Crossing Event MACHO 98-SMC-1

We fit the data for the binary-lens microlensing event MACHO 98-SMC-1 from 5 different microlensing collaborations and find two distinct solutions characterized by binary separation d and mass ratio q: (d,q)=(0.54,0.50) and (d,q)=(3.65,0.36), where d is in units of the Einstein radius. However, the relative proper motion of the lens is very similar in the two solutions, 1.30 km/s/kpc and 1.48 km/s/kpc, thus confirming that the lens is in the Small Magellanic Cloud. The close binary can be either rotating or approximately static but the wide binary must be rotating at close its maximum allowed rate to be consistent with all the data. We measure limb-darkening coefficients for five bands ranging from I to V. As expected, these progressively decrease with rising wavelength. This is the first measurement of limb darkening for a metal-poor A star.Comment: 29 pages + 9 figures + 2 tables, submitted to Ap

Systematic care for caregivers of people with dementia in the ambulatory mental health service: designing a multicentre, cluster, randomized, controlled trial

Contains fulltext : 81435.pdf (publisher's version ) (Open Access)BACKGROUND: Care for people with dementia and their informal caregivers is a challenging aim in healthcare. There is an urgent need for cost-effective support programs that prevent informal caregivers of people with dementia from becoming overburdened, which might result in a delay or decrease of patient institutionalization. For this reason, we have developed the Systematic Care Program for Dementia (SCPD). The SCPD consists of an assessment of caregiver's sense of competence and suggestions on how to deal with competence deficiencies. The efficiency of the SCPD will be evaluated in our study. METHODS AND DESIGN: In our ongoing, cluster, randomized, single-blind, controlled trial, the participants in six mental health services in four regions of the Netherlands have been randomized per service. Professionals of the ambulatory mental health services (psychologists and social psychiatric nurses) have been randomly allocated to either the intervention group or the control group. The study population consists of community-dwelling people with dementia and their informal caregivers (patient-caregiver dyads) coming into the health service. The dyads have been clustered to the professionals. The primary outcome measure is the patient's admission to a nursing home or home for the elderly at 12 months of follow-up. This measure is the most important variable for estimating cost differences between the intervention group and the control group. The secondary outcome measure is the quality of the patient's and caregiver's lives. DISCUSSION: A novelty in the SCPD is the pro-active and systematic approach. The focus on the caregiver's sense of competence is relevant to economical healthcare, since this sense of competence is an important determinant of delay of institutionalization of people with dementia. The SCPD might be able to facilitate this with a relatively small cost investment for caregivers' support, which could result in a major decrease in costs in the management of dementia. Implementation on a national level will be started if the SCPD proves to be efficient. TRIAL REGISTRATION: NCT00147693