Background Checks for Firearm Transfers, 2015 - Statistical Tables

Describes background checks for firearms transfers conducted in 2015 and presents estimates of firearm applications received and denied annually since the effective date of the Brady Act in 1994 through 2015. Statistical tables provide data on the number of firearm applications processed by the FBI and state and local agencies, number of applications denied, reasons for denial, and estimates of applications by jurisdiction and by each type of approval system. Findings are based on data from BJS's Firearm Inquiry Statistics program, which annually surveys state and local background checking agencies to collect information on firearm background check activity and combines this information with the FBI's National Instant Criminal Background Check System transaction data to generate national estimates.Highlights:Since the effective date of the Brady Act on February 28, 1994, through December 31, 2015, nearly 197 million applications for firearm transfers or permits were subject to background checks and more than 3 million applications (1.5%) were denied.Nearly 17 million applications for firearm transfers were received in 2015, up from an estimated 15 million in 2014.About 1.4% of the nearly 17 million applications for firearm transfers or permits in 2015 were denied: about 107,000 by the FBI and about 119,000 by state and local agencies.Among state agency reporters, denial rates in 2015 were 3.0% for purchase permits, 1.5% for instant checks, 1.1% for other approval checks, and 1.1% for exempt carry permits.Local agencies denied 4.2% of applications for purchase permit checks and 1.1% of applications for exempt carry permits

Baseline new bone formation does not predict bone loss in ankylosing spondylitis as assessed by quantitative computed tomography (QCT) - 10-year follow-up

<p>Abstract</p> <p>Background</p> <p>To evaluate the relationship between bone loss and new bone formation in ankylosing spondylitis (AS) using 10-year X-ray, dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) follow-up.</p> <p>Methods</p> <p>Fifteen AS patients free from medical conditions and drugs affecting bone metabolism underwent X-ray, DXA and QCT in 1999 and 2009.</p> <p>Results</p> <p>In spine QCT a statistically significant (p = 0,001) decrease of trabecular bone mineral content (BMC) was observed (change ± SD: 18.0 ± 7.3 mg/cm³). In contrast, spine DXA revealed a significant increase of bone mineral density (change ± SD: -0.15 ± 0.14 g/cm²). The mean BMC, both at baseline and follow-up was significantly lower (p = 0.02 and p = 0.005, respectively) in advanced radiological group as compared to early radiological group. However, in multiple regression model after adjustment for baseline BMC, the baseline radiological scoring did not influence the progression of bone loss as assessed with QCT (p = 0.22, p for BMC*X-ray syndesmophyte scoring interaction = 0.65, p for ANOVA-based X-ray syndesmophyte scoring*time interaction = 0.39). Baseline BMC was the only significant determinant of 10-year BMC change, to date the longest QCT follow-up data in AS.</p> <p>Conclusions</p> <p>In AS patients who were not using antiosteoporotic therapy spine trabecular bone density evaluated by QCT decreased over 10-year follow-up and was not related to baseline radiological severity of spine involvement.</p

Low bone mineral density is related to male gender and decreased functional capacity in early spondylarthropathies

The objective of this study was to determine the prevalence and risk factors of low bone mineral density (BMD) in patients with spondylarthropathies (SpA) at an early stage of disease. In this cross-sectional study, the BMD of lumbar spine and hips was measured in 130 consecutive early SpA patients. The outcome measure BMD was defined as (1) osteoporosis, (2) osteopenia, and (3) normal bone density. Logistic regression analyses were used to investigate relations between the following variables: age, gender, disease duration, diagnosis, HLA-B27, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), extra-spinal manifestations and medication, with outcome measure low BMD (osteopenia and/or osteoporosis). The SpA population had a median time since diagnosis of 6.6 months and a disease duration of 6.3 years. In total, 9% of the early SpA patients had osteoporosis, 38% osteopenia, and 53% normal BMD. On univariate analyses, male gender, diagnosis of ankylosing spondylitis, increased CRP, high BASFI, and high BASMI were significantly associated with low BMD. Factors showing a relation with low BMD in the multivariate model were male gender (OR 4.18, 95% confidence interval (CI) 1.73–10.09), high BASMI (OR 1.54, 95% CI 1.14–2.07), and high BASFI (OR 1.18, 95% CI 1.00–1.39). In early SpA patients, a high frequency (47%) of low BMD in femur as well as in lumbar spine was found. Low BMD was associated with male gender and decreased functional capacity. These findings emphasize the need for more alertness for osteoporosis and osteopenia in spondylarthropathy patients at an early stage of the disease

Mechanisms Used for Genomic Proliferation by Thermophilic Group II Introns

Studies of mobile group II introns from a thermophilic cyanobacterium reveal how these introns proliferate within genomes and might explain the origin of introns and retroelements in higher organisms

Inflammatory Rheumatic Disorders and Bone

Inflammatory joint diseases such as rheumatoid arthritis, as well as other rheumatic conditions, such as systemic lupus erythematosus (SLE) and ankylosing spondylitis, comprise a heterogeneous group of joint disorders that are all associated with extra-articular side effects, including bone loss and fractures. The concept of osteoimmunology is based on growing insights into the links between the immune system and bone. The pathogenesis of osteoporosis in these patients is multifactorial. We have, more or less as an example, described this extensively for patients with SLE. High disease activity (inflammation) and immobility are common factors that substantially increase fracture risk in these patients, on top of the background fracture risk based on, among other factors, age, body mass index, and gender. Although no fracture reduction has been shown in intervention studies in patients with inflammatory rheumatic diseases, we present treatment options that might be useful for clinicians who are treating these patients

The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis

Osteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detect bone loss in AS. The aim of this study was to elucidate the pathophysiology of AS-related osteoporosis by investigating the relation between bone mineral density (BMD), BTM, vitamin D, and clinical assessments of disease activity and physical function, as well as to identify parameters that are related to low BMD (osteopenia or osteoporosis) in AS patients with active disease. One hundred twenty-eight consecutive Dutch AS outpatients were included in this cross-sectional study. Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein, ASAS-endorsed disease activity score (ASDAS), Bath AS Functional Index (BASFI), bone formation markers procollagen type 1 N-terminal peptide (PINP) and osteocalcin (OC), bone resorption marker serum C-telopeptides of type I collagen (sCTX), 25-hydroxyvitamin D (25OHvitD), lumbar spine and hip BMD, and vertebral fractures were assessed. Z-scores of BTM were calculated using matched 10-year cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. sCTX Z-score, OC Z-score, BASDAI, age, and gender were independently related to low BMD. In addition, PINP Z-score, ESR, 25OHvitD, age, and gender were independently related to sCTX and/or OC Z-score. This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis. Furthermore, sCTX and OC Z-scores seem to be valuable markers to detect bone loss in AS patients in daily clinical practice where BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS

Effects of the Histone Deacetylase Inhibitor Valproic Acid on Human Pericytes In Vitro

Microvascular pericytes are of key importance in neoformation of blood vessels, in stabilization of newly formed vessels as well as maintenance of angiostasis in resting tissues. Furthermore, pericytes are capable of differentiating into pro-fibrotic collagen type I producing fibroblasts. The present study investigates the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) on pericyte proliferation, cell viability, migration and differentiation. The results show that HDAC inhibition through exposure of pericytes to VPA in vitro causes the inhibition of pericyte proliferation and migration with no effect on cell viability. Pericyte exposure to the potent HDAC inhibitor Trichostatin A caused similar effects on pericyte proliferation, migration and cell viability. HDAC inhibition also inhibited pericyte differentiation into collagen type I producing fibroblasts. Given the importance of pericytes in blood vessel biology a qPCR array focusing on the expression of mRNAs coding for proteins that regulate angiogenesis was performed. The results showed that HDAC inhibition promoted transcription of genes involved in vessel stabilization/maturation in human microvascular pericytes. The present in vitro study demonstrates that VPA influences several aspects of microvascular pericyte biology and suggests an alternative mechanism by which HDAC inhibition affects blood vessels. The results raise the possibility that HDAC inhibition inhibits angiogenesis partly through promoting a pericyte phenotype associated with stabilization/maturation of blood vessels

Retention on Buprenorphine Is Associated with High Levels of Maximal Viral Suppression among HIV-Infected Opioid Dependent Released Prisoners

HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX) as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD).From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART) for released HIV-infected prisoners; 50 (53%) selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47%) selected no BPN/NLX therapy. Maximum viral suppression (MVS), defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44) groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%), from Hartford (74.4% v 47.7%) and have higher mean global health quality of life indicator scores (54.18 v 51.40). MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1)], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1)] and negatively with being Black [AOR = 0.13 (0.03, 0.68)]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy

Group II Intron-Based Gene Targeting Reactions in Eukaryotes

Mobile group II introns insert site-specifically into DNA target sites by a mechanism termed retrohoming in which the excised intron RNA reverse splices into a DNA strand and is reverse transcribed by the intron-encoded protein. Retrohoming is mediated by a ribonucleoprotein particle that contains the intron-encoded protein and excised intron RNA, with target specificity determined largely by base pairing of the intron RNA to the DNA target sequence. This feature enabled the development of mobile group II introns into bacterial gene targeting vectors ("targetrons") with programmable target specificity. Thus far, however, efficient group II intron-based gene targeting reactions have not been demonstrated in eukaryotes.By using a plasmid-based Xenopus laevis oocyte microinjection assay, we show that group II intron RNPs can integrate efficiently into target DNAs in a eukaryotic nucleus, but the reaction is limited by low Mg(2+) concentrations. By supplying additional Mg(2+), site-specific integration occurs in up to 38% of plasmid target sites. The integration products isolated from X. laevis nuclei are sensitive to restriction enzymes specific for double-stranded DNA, indicating second-strand synthesis via host enzymes. We also show that group II intron RNPs containing either lariat or linear intron RNA can introduce a double-strand break into a plasmid target site, thereby stimulating homologous recombination with a co-transformed DNA fragment at frequencies up to 4.8% of target sites. Chromatinization of the target DNA inhibits both types of targeting reactions, presumably by impeding RNP access. However, by using similar RNP microinjection methods, we show efficient Mg(2+)-dependent group II intron integration into plasmid target sites in zebrafish (Danio rerio) embryos and into plasmid and chromosomal target sites in Drosophila melanogster embryos, indicating that DNA replication can mitigate effects of chromatinization.Our results provide an experimental foundation for the development of group II intron-based gene targeting methods for higher organisms

The Retrohoming of Linear Group II Intron RNAs in Drosophila melanogaster Occurs by Both DNA Ligase 4–Dependent and –Independent Mechanisms

Mobile group II introns are bacterial retrotransposons that are thought to have invaded early eukaryotes and evolved into introns and retroelements in higher organisms. In bacteria, group II introns typically retrohome via full reverse splicing of an excised intron lariat RNA into a DNA site, where it is reverse transcribed by the intron-encoded protein. Recently, we showed that linear group II intron RNAs, which can result from hydrolytic splicing or debranching of lariat RNAs, can retrohome in eukaryotes by performing only the first step of reverse splicing, ligating their 3′ end to the downstream DNA exon. Reverse transcription then yields an intron cDNA, whose free end is linked to the upstream DNA exon by an error-prone process that yields junctions similar to those formed by non-homologous end joining (NHEJ). Here, by using Drosophila melanogaster NHEJ mutants, we show that linear intron RNA retrohoming occurs by major Lig4-dependent and minor Lig4-independent mechanisms, which appear to be related to classical and alternate NHEJ, respectively. The DNA repair polymerase θ plays a crucial role in both pathways. Surprisingly, however, mutations in Ku70, which functions in capping chromosome ends during NHEJ, have only moderate, possibly indirect effects, suggesting that both Lig4 and the alternate end-joining ligase act in some retrohoming events independently of Ku. Another potential Lig4-independent mechanism, reverse transcriptase template switching from the intron RNA to the upstream exon DNA, occurs in vitro, but gives junctions differing from the majority in vivo. Our results show that group II introns can utilize cellular NHEJ enzymes for retromobility in higher organisms, possibly exploiting mechanisms that contribute to retrotransposition and mitigate DNA damage by resident retrotransposons. Additionally, our results reveal novel activities of group II intron reverse transcriptases, with implications for retrohoming mechanisms and potential biotechnological applications