Proper Motions in the Galactic Bulge: Plaut's Window

A proper motion study of a field of 20' x 20' inside Plaut's low extinction window (l,b)=(0 deg,-8 deg), has been completed. Relative proper motions and photographic BV photometry have been derived for ~21,000 stars reaching to V~20.5 mag, based on the astrometric reduction of 43 photographic plates, spanning over 21 years of epoch difference. Proper motion errors are typically 1 mas/yr and field dependent systematics are below 0.2 mas/yr. Cross-referencing with the 2MASS catalog yielded a sample of ~8,700 stars, from which predominantly disk and bulge subsamples were selected photometrically from the JH color-magnitude diagram. The two samples exhibited different proper-motion distributions, with the disk displaying the expected reflex solar motion as a function of magnitude. Galactic rotation was also detected for stars between ~2 and ~3 kpc from us. The bulge sample, represented by red giants, has an intrinsic proper motion dispersion of (sigma_l,sigma_b)=(3.39, 2.91)+/-(0.11,0.09) mas/yr, which is in good agreement with previous results, and indicates a velocity anisotropy consistent with either rotational broadening or tri-axiality. A mean distance of 6.37^{+0.87}_{-0.77} kpc has been estimated for the bulge sample, based on the observed K magnitude of the horizontal branch red clump. The metallicity [M/H] distribution was also obtained for a subsample of 60 bulge giants stars, based on calibrated photometric indices. The observed [M/H] shows a peak value at [M/H]~-0.1 with an extended metal poor tail and around 30% of the stars with supersolar metallicity. No change in proper motion dispersion was observed as a function of [M/H]. We are currently in the process of obtaining CCD UBVRI photometry for the entire proper-motion sample of ~21,000 stars.Comment: Submitted to AJ April 17th 2007. Accepted June 8th 2007. 45 pages, 14 figure

Defining a recovery-oriented cascade of care for opioid use disorder: A community-driven, statewide cross-sectional assessment

Background In light of the accelerating and rapidly evolving overdose crisis in the United States (US), new strategies are needed to address the epidemic and to efficiently engage and retain individuals in care for opioid use disorder (OUD). Moreover, there is an increasing need for novel approaches to using health data to identify gaps in the cascade of care for persons with OUD. Methods and findings Between June 2018 and May 2019, we engaged a diverse stakeholder group (including directors of statewide health and social service agencies) to develop a statewide, patient-centered cascade of care for OUD for Rhode Island, a small state in New England, a region highly impacted by the opioid crisis. Through an iterative process, we modified the cascade of care defined by Williams et al. for use in Rhode Island using key national survey data and statewide health claims datasets to create a cross-sectional summary of 5 stages in the cascade. Approximately 47,000 Rhode Islanders (5.2%) were estimated to be at risk for OUD (stage 0) in 2016. At the same time, 26,000 Rhode Islanders had a medical claim related to an OUD diagnosis, accounting for 55% of the population at risk (stage 1); 27% of the stage 0 population, 12,700 people, showed evidence of initiation of medication for OUD (MOUD, stage 2), and 18%, or 8,300 people, had evidence of retention on MOUD (stage 3). Imputation from a national survey estimated that 4,200 Rhode Islanders were in recovery from OUD as of 2016, representing 9% of the total population at risk. Limitations included use of self-report data to arrive at estimates of the number of individuals at risk for OUD and using a national estimate to identify the number of individuals in recovery due to a lack of available state data sources. Conclusions Our findings indicate that cross-sectional summaries of the cascade of care for OUD can be used as a health policy tool to identify gaps in care, inform data-driven policy decisions, set benchmarks for quality, and improve health outcomes for persons with OUD. There exists a significant opportunity to increase engagement prior to the initiation of OUD treatment (i.e., identification of OUD symptoms via routine screening or acute presentation) and improve retention and remission from OUD symptoms through improved community-supported processes of recovery. To do this more precisely, states should work to systematically collect data to populate their own cascade of care as a health policy tool to enhance system-level interventions and maximize engagement in care

Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA.

Diarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and sub-Saharan Africa, where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long-term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, and yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh, namely, the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for length-for-age Z-score at 12 months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P = 3.73 × 10-8), an intronic SNP and expression quantitative trait locus (eQTL) of protein kinase C alpha (PRKCA). Each additional risk allele conferred 2.4 times the odds of Cryptosporidium-associated diarrhea in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation.IMPORTANCE Globally, diarrhea remains one of the major causes of pediatric morbidity and mortality. The initial symptoms of diarrhea can often lead to long-term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here, we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase C alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism

Survival following gamma knife radiosurgery for brain metastasis from breast cancer

BACKGROUND: Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. METHODS: A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. RESULTS: Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival. CONCLUSION: Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

BACKGROUND: While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. METHODS: Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. RESULTS: Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. CONCLUSION: Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence

Report of Seminar on Law and Medicine

Reports from the UK/CLE Seminar on Law and Medicine held May 26-28, 1976

Integrated Spectroscopy of Bulge Globular Clusters and Fields. II. Implications for stellar population models and elliptical galaxies

Synthetic Lick indices (e.g. Mg_2, Fe, etc.) of Simple Stellar Population (SSP) models are calibrated for the first time up to solar metallicity with a sample of Milky Way globular clusters (GCs) which includes the metal rich GCs of the Galactic bulge. This metallicity range is relevant to elliptical galaxies. It is shown that the Bulge GCs and integrated light follow the same correlation between Mg and Fe indices of elliptical galaxies, showing weaker Fe indices at given Mg indices with respect to models that assume solar-scaled abundances. This similarity is the robust empirical evidence for enhanced alpha/Fe ratios in the stellar populations of elliptical galaxies, since the globular clusters are independently known to be alpha-enhanced. The uniqueness of this alpha-overabundance solution is checked by exploring the whole range of model ingredients. We argue that the standard models reproduce the Mg-Fe correlation at low metallicities because the stellar templates used in the synthesis are the alpha-enhanced stars of the galactic Halo. These same models, however, fail to recover the Mg-Fe pattern of Bulge clusters and ellipticals at high metallicities because the high-metallicity templates are disk stars, which are not alpha-enhanced. The new SSP models by Thomas, Maraston & Bender (2002) which incorporate the dependence on alpha/Fe reproduce the Mg and Fe indices of GCs at all metallicities, with alpha/Fe=+0.3, which is in agreement with spectroscopic abundance determinations. The Balmer indices (Hbeta, Hdelta, Hgamma) are very well calibrated, provided the Horizontal Branch morphology is taken into account. In particular, we reproduce the Balmer lines of NGC 6388 and NGC 6441, which are metal-rich GCs with a tail of warm Horizontal Branch stars. {Abridged}Comment: 19 pages, 13 figures, Astronomy and Astrophysics in press. Only minor changes after the referee repor

Integration of kinase and calcium signaling at the level of chromatin underlies inducible gene activation in T cells

TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression. We found that these regions typically function as inducible enhancers. Many of these elements contain composite NFAT/AP-1 sites, which typically support cooperative binding, thus further reinforcing the need for cooperation between calcium and kinase signaling in the activation of genes in T cells. In contrast, treatment with PMA or ionomycin alone induces chromatin remodeling at far fewer regions (∼600 and ∼350, respectively), which mostly represent a subset of those induced by costimulation. This suggests that the integration of TCR signaling largely occurs at the level of chromatin, which we propose plays a crucial role in regulating T cell activation

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)