Behavioral risk profiles of homeschooled adolescents in the United States: a nationally representative examination of substance use related outcomes

BACKGROUND: The homeschool population continues to grow in size and now accounts for 3.4% of all students in the United States. OBJECTIVE: Given the heterogeneous nature of the population, this study examines the relationship between different types of homeschoolers and a number of substance use related outcomes. METHODS: To conduct this study, we used pooled data (2002–2013) from the National Survey on Drug Use and Health (NSDUH). Respondents aged 12–17 who reported they had been homeschooled at any time during the previous 12 months were classified as homeschoolers (N = 1,321). Latent profile analysis (LPA) was conducted to identify latent subgroups of homeschoolers and multinomial regression was executed to assess the relationship between the subgroups and perceived substance use risk, availability, and past 12-month use. RESULTS: The LPA yielded four subgroups, which were summarized as (1) highly religious and engaged, (2) limited parental monitoring, (3) high parental warmth and support, and (4) secular permissive. Of these, the highly religious and engaged subgroup was the least likely to report using substances. CONCLUSION: The results underscore the variation that exists among homeschoolers and the importance of examining the relationship between different types of homeschoolers and outcomes of interest

Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential.

BackgroundMetastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning > 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.MethodsPNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).ResultsThe CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.ConclusionsMeasuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis

Three years of Fermi GBM Earth Occultation Monitoring: Observations of Hard X-ray/Soft Gamma-Ray Sources

The Gamma ray Burst Monitor (GBM) on board Fermi has been providing continuous data to the astronomical community since 2008 August 12. In this paper we present the results of the analysis of the first three years of these continuous data using the Earth occultation technique to monitor a catalog of 209 sources. From this catalog, we detect 99 sources, including 40 low-mass X-ray binary/neutron star systems, 31 high-mass X-ray binary neutron star systems, 12 black hole binaries, 12 active galaxies, 2 other sources, plus the Crab Nebula, and the Sun. Nine of these sources are detected in the 100-300 keV band, including seven black-hole binaries, the active galaxy Cen A, and the Crab. The Crab and Cyg X-1 are also detected in the 300-500 keV band. GBM provides complementary data to other sky-monitors below 100 keV and is the only all-sky monitor above 100 keV. Up-to-date light curves for all of the catalog sources can be found at http://heastro.phys.lsu.edu/gbm/.Comment: 24 pages, 12 figures, accepted for publication in ApJ

Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe_(49.7)Cr_(17.7)Mn_(1.9)Mo_(7.4)W_(1.6)B_(15.2)C_(3.8)Si_(2.4). The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding

Calibration of the GLAST Burst Monitor detectors

The GLAST Burst Monitor (GBM) will augment the capabilities of GLAST for the detection of cosmic gamma-ray bursts by extending the energy range (20 MeV to > 300 GeV) of the Large Area Telescope (LAT) towards lower energies by 2 BGO-detectors (150 keV to 30 MeV) and 12 NaI(Tl) detectors (10 keV to 1 MeV). The physical detector response of the GBM instrument for GRBs is determined with the help of Monte Carlo simulations, which are supported and verified by on-ground calibration measurements, performed extensively with the individual detectors at the MPE in 2005. All flight and spare detectors were irradiated with calibrated radioactive sources in the laboratory (from 14 keV to 4.43 MeV). The energy/channel-relations, the dependences of energy resolution and effective areas on the energy and the angular responses were measured. Due to the low number of emission lines of radioactive sources below 100 keV, calibration measurements in the energy range from 10 keV to 60 keV were performed with the X-ray radiometry working group of the Physikalisch-Technische Bundesanstalt (PTB) at the BESSY synchrotron radiation facility, Berlin.Comment: 2 pages, 1 figure; to appear in the Proc. of the First Int. GLAST Symp. (Stanford, Feb. 5-8, 2007), eds. S.Ritz, P.F.Michelson, and C.Meegan, AIP Conf. Pro

Hyperproliferation and Dysregulation ofIL-4 Expression in NF-ATp-Deficient Mice

AbstractNF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and FasL. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM–CSF, and TNFα was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFNγ were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.BDY

Extraterrestrial Prebiotic Molecules: Photochemistry vs. Radiation Chemistry of Interstellar Ices

In 2016, unambiguous evidence for the presence of the amino acid glycine, an important prebiotic molecule, was deduced based on in situ mass-spectral studies of the coma surrounding cometary ice. This finding is significant because comets are thought to have preserved the icy grains originally found in the interstellar medium prior to solar system formation. Energetic processing of cosmic ices via photochemistry and radiation chemistry is thought to be the dominant mechanism for the extraterrestrial synthesis of prebiotic molecules. Radiation chemistry is defined as the “study of the chemical changes produced by the absorption of radiation of sufficiently high energy to produce ionization.” Ionizing radiation in cosmic chemistry includes high-energy particles (e.g., cosmic rays) and high-energy photons (e.g., extreme-UV). In contrast, photochemistry is defined as chemical processes initiated by photon-induced electronic excitation not involving ionization. Vacuum-UV (6.2 –12.4 eV) light may, in addition to photochemistry, initiate radiation chemistry because the threshold for producing secondary electrons is lower in the condensed phase than in the gas phase. Unique to radiation chemistry are four phenomena: (1) production of a cascade of low-energy (\u3c 20 eV) secondary electrons which are thought to be the dominant driving force for radiation chemistry, (2) reactions initiated by cations, (3) non-uniform distribution of reaction intermediates, and (4) non-selective chemistry leading to the production of multiple reaction products. The production of low-energy secondary electrons during radiation chemistry may also lead to new reaction pathways not available to photochemistry. In addition, low-energy electron-induced radiation chemistry may predominate over photochemistry because of the sheer number of low-energy secondary electrons. Moreover, reaction cross-sections can be several orders of magnitude larger for electrons than for photons. Discerning the role of photochemistry vs. radiation chemistry in astrochemistry is challenging because astrophysical photoninduced chemistry studies have almost exclusively used light sources that produce \u3e 10 eV photons. Because a primary objective of chemistry is to provide molecular-level mechanistic explanations for macroscopic phenomena, our ultimate goal in this review paper is to critically evaluate our current understanding of cosmic ice energetic processing which likely leads to the synthesis of extraterrestrial prebiotic molecules

Search for Magnetic Monopoles Trapped in Matter

There have been many searches for magnetic monopoles in flight, but few for monopoles in matter. We have searched for magnetic monopoles in meteorites, schists, ferromanganese nodules, iron ores and other materials. The detector was a superconducting induction coil connected to a SQUID (Superconducting Quantum Interference Device) with a room temperature bore 15 cm in diameter. We tested a total of more than 331 kg of material including 112 kg of meteorites. We found no monopole and conclude the overall monopole/nucleon ratio in the samples is $<1.2 \times 10^{-29}$ with a 90\% confidence level.Comment: 6 pages, rev tex, no figure

Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice

Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction