Community Capacity Building: Supporting Military Children and Families Environmental Scan of Extension Professional Development Opportunities for Early Childhood and School-Age Providers: Final Report

The purpose of this environmental scan was to discover what professional development is offered through the Cooperative Extension System to early childhood or school age providers across the nation. A secondary focus was to assess the availability of professional development opportunities offered through the Cooperative Extension System for providers who serve children (birth–12) from military families, both on and off installation. Through this process, the strengths of Extension were highlighted and existing resources that could be replicated for use in other states were identified

Multifaceted empathy differences in children and adults with autism

Although empathy impairments have been reported in autistic individuals, there is no clear consensus on how emotional valence influences this multidimensional process. In this study, we use the Multifaceted Empathy Test for juveniles (MET-J) to interrogate emotional and cognitive empathy in 184 participants (ages 8–59 years, 83 autistic) under the robust Bayesian inference framework. Group comparisons demonstrate previously unreported interaction effects between: (1) valence and autism diagnosis in predictions of emotional resonance, and (2) valence and age group in predictions of arousal to images portraying positive and negative facial expressions. These results extend previous studies using the MET by examining differential effects of emotional valence in a large sample of autistic children and adults with average or above-average intelligence. We report impaired cognitive empathy in autism, and subtle differences in emotional empathy characterized by less distinction between emotional resonance to positive vs. negative facial expressions in autism compared to neurotypicals. Reduced emotional differentiation between positive and negative affect in others could be a mechanism for diminished social reciprocity that poses a universal challenge for people with autism. These component- and valence- specific findings are of clinical relevance for the development and implementation of target-specific social interventions in autism

The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

We describe the design and data sample from the DEEP2 Galaxy Redshift Survey, the densest and largest precision-redshift survey of galaxies at z ~ 1 completed to date. The survey has conducted a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude M_B = -20 at z ~ 1 via ~90 nights of observation on the DEIMOS spectrograph at Keck Observatory. DEEP2 covers an area of 2.8 deg^2 divided into four separate fields, observed to a limiting apparent magnitude of R_AB=24.1. Objects with z < 0.7 are rejected based on BRI photometry in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted ~2.5 times more efficiently than in a purely magnitude-limited sample. Approximately sixty percent of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets which fail to yield secure redshifts are blue objects that lie beyond z ~ 1.45. The DEIMOS 1200-line/mm grating used for the survey delivers high spectral resolution (R~6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. DEEP2 surpasses other deep precision-redshift surveys at z ~ 1 in terms of galaxy numbers, redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the publicly-available DEEP2 DEIMOS data reduction pipelines. [Abridged]Comment: submitted to ApJS; data products available for download at http://deep.berkeley.edu/DR4

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Three Dimensional Structure of the MqsR:MqsA Complex: A Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties

One mechanism by which bacteria survive environmental stress is through the formation of bacterial persisters, a sub-population of genetically identical quiescent cells that exhibit multidrug tolerance and are highly enriched in bacterial toxins. Recently, the Escherichia coli gene mqsR (b3022) was identified as the gene most highly upregulated in persisters. Here, we report multiple individual and complex three-dimensional structures of MqsR and its antitoxin MqsA (B3021), which reveal that MqsR:MqsA form a novel toxin:antitoxin (TA) pair. MqsR adopts an α/β fold that is homologous with the RelE/YoeB family of bacterial ribonuclease toxins. MqsA is an elongated dimer that neutralizes MqsR toxicity. As expected for a TA pair, MqsA binds its own promoter. Unexpectedly, it also binds the promoters of genes important for E. coli physiology (e.g., mcbR, spy). Unlike canonical antitoxins, MqsA is also structured throughout its entire sequence, binds zinc and coordinates DNA via its C- and not N-terminal domain. These studies reveal that TA systems, especially the antitoxins, are significantly more diverse than previously recognized and provide new insights into the role of toxins in maintaining the persister state

Dust Reverberation Mapping in Distant Quasars from Optical and Mid-Infrared Imaging Surveys

The size of the dust torus in Active Galactic Nuclei (AGN) and their high-luminosity counterparts, quasars, can be inferred from the time delay between UV/optical accretion disk continuum variability and the response in the mid-infrared (MIR) torus emission. This dust reverberation mapping (RM) technique has been successfully applied to $\sim 70$ $z\lesssim 0.3$ AGN and quasars. Here we present first results of our dust RM program for distant quasars covered in the SDSS Stripe 82 region combining $\sim 20$-yr ground-based optical light curves with 10-yr MIR light curves from the WISE satellite. We measure a high-fidelity lag between W1-band (3.4 $\mu$m) and $g$ band for 587 quasars over $0.3\lesssim z\lesssim 2$ (\left\sim 0.8) and two orders of magnitude in quasar luminosity. They tightly follow (intrinsic scatter $\sim 0.17$ dex in lag) the IR lag-luminosity relation observed for $z<0.3$ AGN, revealing a remarkable size-luminosity relation for the dust torus over more than four decades in AGN luminosity, with little dependence on additional quasar properties such as Eddington ratio and variability amplitude. This study motivates further investigations in the utility of dust RM for cosmology, and strongly endorses a compelling science case for the combined 10-yr Vera C. Rubin Observatory Legacy Survey of Space and Time (optical) and 5-yr Nancy Grace Roman Space Telescope 2$\mu$m light curves in a deep survey for low-redshift AGN dust RM with much lower luminosities and shorter, measurable IR lags. The compiled optical and MIR light curves for 7,384 quasars in our parent sample are made public with this work.Comment: Accepted for publication in Ap