Chromatin proteins and RNA are associated with DNA during all phases of mitosis.

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein-DNA and RNA-DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains

Hormonal and Sex Impact on the Epidemiology of Canine Lymphoma

The Surveillance Epidemiology and End Results data demonstrate that the risk of non-Hodgkin lymphoma is lower for women, but that the incidence increases after fifty years of age, at which menopause is regularly reached, suggesting that female hormones may be protective for NHL. This study examines the influence of sex on lymphoma risk in a relevant large animal model. Records for dogs in the Veterinary Medical Database were analyzed from 1964 to 2002. Risk ratios were calculated to evaluate associations between sex, neutering status, and lymphoma occurrence. A total of 14,573 cases and 1,157,342 controls were identified. Intact females had a significantly lower risk of developing lymphoma, Odds Ratio 0.69 (0.63–0.74) with a P < .001. We conclude that there is a sex effect on NHL risk in dogs similar to humans. We hypothesize that the hormone levels of intact females lower the risk of NHL. The possibility of a protective role of endogenous estrogens in the etiology of NHL should be investigated

Data Reduction Pipeline for the CHARIS Integral-Field Spectrograph I: Detector Readout Calibration and Data Cube Extraction

We present the data reduction pipeline for CHARIS, a high-contrast integral-field spectrograph for the Subaru Telescope. The pipeline constructs a ramp from the raw reads using the measured nonlinear pixel response, and reconstructs the data cube using one of three extraction algorithms: aperture photometry, optimal extraction, or $\chi^2$ fitting. We measure and apply both a detector flatfield and a lenslet flatfield and reconstruct the wavelength- and position-dependent lenslet point-spread function (PSF) from images taken with a tunable laser. We use these measured PSFs to implement a $\chi^2$-based extraction of the data cube, with typical residuals of ~5% due to imperfect models of the undersampled lenslet PSFs. The full two-dimensional residual of the $\chi^2$ extraction allows us to model and remove correlated read noise, dramatically improving CHARIS' performance. The $\chi^2$ extraction produces a data cube that has been deconvolved with the line-spread function, and never performs any interpolations of either the data or the individual lenslet spectra. The extracted data cube also includes uncertainties for each spatial and spectral measurement. CHARIS' software is parallelized, written in Python and Cython, and freely available on github with a separate documentation page. Astrometric and spectrophotometric calibrations of the data cubes and PSF subtraction will be treated in a forthcoming paper.Comment: 18 pages, 15 figures, 3 tables, replaced with JATIS accepted version (emulateapj formatted here). Software at https://github.com/PrincetonUniversity/charis-dep and documentation at http://princetonuniversity.github.io/charis-de

Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools

Background: Low absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasibility of classroom humidification to levels that could decrease viral survival have not been studied. Methods: Automated sensors were used to measure temperature, humidity and CO2 levels in two Minnesota grade schools without central humidification during two successive winters. Outdoor AH measurements were derived from the North American Land Data Assimilation System. Variability in indoor AH within classrooms, between classrooms in the same school, and between schools was assessed using concordance correlation coefficients (CCC). Predictors of indoor AH were examined using time-series Auto-Regressive Conditional Heteroskedasticity models. Classroom humidifiers were used when school was not in session to assess the feasibility of increasing indoor AH to levels associated with decreased influenza virus survival, as projected from previously published animal experiments. Results: AH varied little within classrooms (CCC >0.90) but was more variable between classrooms in the same school (CCC 0.81 for School 1, 0.88 for School 2) and between schools (CCC 0.81). Indoor AH varied widely during the winter (range 2.60 to 10.34 millibars [mb]) and was strongly associated with changes in outdoor AH (p < 0.001). Changes in indoor AH on school weekdays were strongly associated with CO2 levels (p < 0.001). Over 4 hours, classroom humidifiers increased indoor AH by 4 mb, an increase sufficient to decrease projected 1-hour virus survival by an absolute value of 30% during winter months. Conclusions: During winter, indoor AH in non-humidified grade schools varies substantially and often to levels that are very low. Indoor results are predicted by outdoor AH over a season and CO2 levels (which likely reflects human activity) during individual school days. Classroom humidification may be a feasible approach to increase indoor AH to levels that may decrease influenza virus survival and transmission

High-Velocity Line Forming Regions in the Type Ia Supernova 2009ig

We report measurements and analysis of high-velocity (> 20,000 km/s) and photospheric absorption features in a series of spectra of the Type Ia supernova (SN) 2009ig obtained between -14d and +13d with respect to the time of maximum B-band luminosity. We identify lines of Si II, Si III, S II, Ca II and Fe II that produce both high-velocity (HVF) and photospheric-velocity (PVF) absorption features. SN 2009ig is unusual for the large number of lines with detectable HVF in the spectra, but the light-curve parameters correspond to a slightly overluminous but unexceptional SN Ia (M_B = -19.46 mag and Delta_m15 (B) = 0.90 mag). Similarly, the Si II lambda_6355 velocity at the time of B-max is greater than "normal" for a SN Ia, but it is not extreme (v_Si = 13,400 km/s). The -14d and -13d spectra clearly resolve HVF from Si II lambda_6355 as separate absorptions from a detached line forming region. At these very early phases, detached HVF are prevalent in all lines. From -12d to -6d, HVF and PVF are detected simultaneously, and the two line forming regions maintain a constant separation of about 8,000 km/s. After -6d all absorption features are PVF. The observations of SN 2009ig provide a complete picture of the transition from HVF to PVF. Most SN Ia show evidence for HVF from multiple lines in spectra obtained before -10d, and we compare the spectra of SN 2009ig to observations of other SN. We show that each of the unusual line profiles for Si II lambda_6355 found in early-time spectra of SN Ia correlate to a specific phase in a common development sequence from HVF to PVF.Comment: 19 pages, 11figures, 4 tables, submitted to Ap

An empirical approach to assessing pediatric residents\u27 attitudes, knowledge, and skills in primary care behavioral health

This paper describes an empirical approach to assessing pediatric residents\u27 attitudes, knowledge and skills in primary care behavioral health. Outcomes from that assessment approach are presented from two pediatric residency training programs in the northeastern United States. Thirty-six pediatric residents completed attitudes, knowledge and skills surveys. The survey was developed to align with the American Academy of Pediatrics’ Policy Statement in 2009 citing aspirational competencies for pediatricians in primary care behavioral health. This alignment addressed both learner variables (attitudes, knowledge, and skills) as well as clinical presentations (ADHD, anxiety, depression, and suicide) highlighted in the policy statement. The survey specifically inquired about self-reported confidence and comfort in managing behavioral health concerns using evidence-based practice parameters (attitudes and knowledge) and their measured ability to deliver evidence-based care in response to clinical vignettes (skills). Findings largely revealed no statistically significant differences in attitudes, knowledge or skills between interns and upper-level residents. Training programs can use the approach described in this paper and the assessment instrument with some possible modifications to monitor annual progress and evaluate any changes in didactic and clinical training

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3&nbsp;years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6&nbsp;months (median). The median age was 72&nbsp;years, and the baseline median prostate-specific antigen level was 15.0&nbsp;ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7&nbsp;months (95% confidence interval [CI], 28.6-32.2&nbsp;months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7&nbsp;months (95% CI, 39.4-46.2&nbsp;months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

As a Pediatrician, I Don’t Know the Second, Third, or Fourth Thing to Do: A Qualitative Study of Pediatric Residents’ Training and Experiences in Behavioral Health

Despite a mandated 1-month rotation in developmental-behavioral pediatrics (DBP), pediatric residents report inadequate training in behavioral health care. As a first step in much needed curriculum development in this area, this study sought to assess learner experiences regarding the management of behavioral health problems during residency. Four focus groups were conducted for residents in years 1-3 of training in 2 residency programs in a northeastern state. Transcripts were analyzed and coded by researchers through qualitative classical content analysis. The exploratory analysis revealed 9 key themes: time requirements, rapport building, resources and referrals for behavioral health, psychiatric medications, diagnosis vs. treatment, working with families, the importance of behavioral health, fears of working with a pediatric population, and training issues. These qualitative data further identify gaps in the behavioral health training of pediatric residents and may inform future innovations in training curricula