Predictors of quit attempts among smokers enrolled in substance abuse treatment

Introduction: This study investigates factors predicting past year quit attempts among smokers enrolled in substance abuse treatment in New York State. Methods: Data were drawn from two prior cross-sectional surveys conducted among clients treated in 10 randomly selected substance abuse treatment programs. Among 820 clients recruited, 542 self-identified as current smokers, and 485 provided information about their quit attempts. The main outcome was reporting a quit smoking attempt in the past year, dichotomized as quit attempters or non-quit attempters. Univariate and multivariate logistic regression analyses were performed to explore predictors of attempting to quit. Results: Half of substance abuse clients in treatment programs reported a past year quit attempt. Quit attempters were more likely to be in a preparation and contemplation stage of change (preparation: OR = 2.68,95% CI: 1.51-4.77; contemplation: OR = 2.96 95% CI: 1.61-5.42), reported more positive attitudes toward quitting (OR = 1.49; 95% CI: 1.11-1.99) and received more cessation services than non-quit attempters (OR = 1.21; 95% Cl: 1.11-1.99). Conclusions: Addressing patient attitudes about quitting smoking, having clinicians address smoking in the course of addiction treatment, and offering interventions to increase readiness to quit may contribute to increased quit attempts in smokers enrolled in addiction treatment programs. (C) 2014 Elsevier Ltd. All rights reserved

An International Systematic Review of Smoking Prevalence in Addiction Treatment

Aims: Smoking prevalence is higher among people enrolled in addiction treatment compared with the general population, and very high rates of smoking are associated with opiate drug use and receipt of opiate replacement therapy (ORT). We assessed whether these findings are observed internationally. Methods: PubMed, PsycINFO and the Alcohol and Alcohol Problems Science Database were searched for papers reporting smoking prevalence among addiction treatment samples, published in English, from 1987 to 2013. Search terms included tobacco use, cessation and substance use disorders using and/or Boolean connectors. For 4549 papers identified, abstracts were reviewed by multiple raters; 239 abstracts met inclusion criteria and these full papers were reviewed for exclusion. Fifty-four studies, collectively comprising 37364 participants, were included. For each paper we extracted country, author, year, sample size and gender, treatment modality, primary drug treated and smoking prevalence. Results: The random-effect pooled estimate of smoking across people in addiction treatment was 84% [confidence interval (CI)=79, 88%], while the pooled estimate of smoking prevalence across matched population samples was 31% (CI=29, 33%). The difference in the pooled estimates was 52% (CI=48%, 57%, P<.0001). Smoking rates were higher in programs treating opiate use compared with alcohol use [odds ratio (OR)=2.52, CI=2.00, 3.17], and higher in ORT compared to out-patient programs (OR=1.42, CI=1.19, 1.68). Conclusions: Smoking rates among people in addiction treatment are more than double those of people with similar demographic characteristics. Smoking rates are also higher in people being treated for opiate dependence compared with people being treated for alcohol use disorder

Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers

AbstractBackground & Aims: Colorectal tumors manifesting high-frequency microsatellite instability (MSI-H) develop genetically as a consequence of mutations in genes harboring repetitive DNA sequences. The activin type 2 receptor (ACVR2), possessing 2 polyadenine coding sequences, was identified as a mutational target, but it is not clear if expression is abrogated. Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs. Methods: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A8 tracts (exon 3 and 10) of ACVR2 and the A10 tract of transforming growth factor β receptor 2 (TGFBR2). Additionally, we sequenced exon 10 of ACVR2 in select cancers. ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein. Results: Forty-five of 54 MSI-H cancers (83%) showed mutation (A8 to A7) in the polyadenine tract of exon 10 compared with no MSS tumors. Of tumors with mutant ACVR2, 62% lacked protein expression but all MSS and MSI-H tumors with wild-type ACVR2 expressed protein. We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors. Comparatively, 69% of MSI-H cancers had frameshift mutation in TGFBR2. Conclusions: ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene. Loss of activin signaling through mutation of ACVR2, similar to observations with TGFBR2, may be important in the genesis of MSI-H colorectal cancer

Elgvandringer i grenseland med følger for skogbruk, jakt og rovdyr

Forvaltning av elg i områder med en delvis trekkende elgbestand byr på utfordringer, fordi kostnadene i form av beiteskader på skogen og goder i form av elgjakt ofte berører forskjellige grunneiere. Dette blir ytterligere komplisert når elgtrekket går på tvers av forvaltningsinndelinger eller til og med over riksgrensen. GRENSEVILT har studert samspillet mellom elg, ulv, skogbruk og jakt i nordre Finnskogen, et stort barskogsområde som er delt av riksgrensen. For å berenge størrelsenpå elgbestanden og beskrive den romlige fordelingen av elg for vintrene 2019/20 og 2020/21, samt somrene 2020 og 2021,har vi gjennomført elgmøkktellinger over et areal på mer enn 3500 km2. Vi ønsket også å studere hvordan elgtrekket påvirker ulvens områdebruk, beitepå furu, og jaktuttaket. Derfor har vived hjelp av GPS-halsbånd analysert områdebruken til fire ulveflokker i samme område. Dessuten gjennomførte vi på våren 2021 en stor beitetakst som kombinerte den norke Solbraa-og den svenske Äbin-metoden. Til slutt har vi sammenstilt jaktdata fra norske vald og svenske älgjaktområder for jaktårene 2019/20 og 2020/21.Vi beregnet elgens tetthet for tidsserien vinter 2019/20, sommer 2020, vinter 2020/21, og sommer 2021 til henholdsvis 1,18, 1,37, 1,01, og 1,70dyr/km2. Om sommeren var elgen noksåjevnt fordelt over hele studieområdet, og om vinteren stod elgen mer konsentrert i de snøfattige områdene, mens det var lite elgi de nordlige, snørike områdene. Til tross for at elgens fordeling endret seg mellom sommer og vinter, opprettholdt ulveflokkene de samme revirgrensene gjennom hele året. Derimot tilpasset de sine aktivitetsområder innenfor revirgrensene til endringen i elgfordelingen. Elgens vinterkonsentrasjonsområder var kjennetegnet ved et større beitetrykk på furu. Skader på produksjontrær var mest hyppig langs dalbunnen og i områder med mye lauvkratt, men vi fant ikke noe tydelig sammenheng mellom skadegrad og elgens vinterfordeling. Elgens effekt på skogbruk målt med den norske Solbraa-metoden viste at beitegraden på furu var stort sett liten. Den svenske Äbin-metoden tegnet et helt motsatt bilde, og bedømmetskadegraden på de samme prøveflatenesomsvært alvorlig. Jaktuttaket i jaktområdene gjenspeilet fordelingen av elg sommerstid i Norge, men ikke i Sverige, der det ble skutt mest elg i områdene med lavest sommertetthet. De hardest beskattede jaktområdene i Sverige hadde en lavere elgtetthet vinteren etter jakt. Vi fant ikke noensammenheng mellom beite-eller skadegrad på furu og jaktuttak i jaktområdene. I den østlige delen av studieområdet som har et stort innslag av trekkelg som oppholder seg på norsk side på sommeren og under jakta, men trekker til Sverige når snøen hoper seg opp lenger nord, var det en tydelig mismatch i forvaltningen av elg mellom de to landene. Mens man i Sverige satset på et høyt jaktuttak for å få bukt med beiteskader,og i tillegg beskattet trekkelg ved januarjakt,sparte man på avskytingen på norsk side fordi beitegraden ikke var bekymringverdigog elgens sommerbestand også ble utsatt for ulvens uttak i tillegg til vinterjakt på svensk side .Vi foreslår en bedre samordning av elgforvaltningen på tvers av riksgrensen. Det krever dialog og samarbeid mellom rettighetshaverne. Et felles elgforvaltningsområde som strekker seg over grensen og dekker trekkelgens helårsområde hadde gjort et slikt samarbeid enklere. Dessuten foreslår vi en samordning av beitetakstmetoden og en felles trafikklysmodell som baserer seg på tetthet av uskadde produksjonstrær heller enn beite-eller skadegraden

R-gene variation across Arabidopsis lyrata subspecies: effects of population structure, selection and mating system.

BACKGROUND: Examining allelic variation of R-genes in closely related perennial species of Arabidopsis thaliana is critical to understanding how population structure and ecology interact with selection to shape the evolution of innate immunity in plants. We finely sampled natural populations of Arabidopsis lyrata from the Great Lakes region of North America (A. l. lyrata) and broadly sampled six European countries (A. l. petraea) to investigate allelic variation of two R-genes (RPM1 and WRR4) and neutral genetic markers (Restriction Associated DNA sequences and microsatellites) in relation to mating system, phylogeographic structure and subspecies divergence. RESULTS: Fine-scale sampling of populations revealed strong effects of mating system and population structure on patterns of polymorphism for both neutral loci and R-genes, with no strong evidence for selection. Broad geographic sampling revealed evidence of balancing selection maintaining polymorphism in R-genes, with elevated heterozygosity and diversity compared to neutral expectations and sharing of alleles among diverged subspecies. Codon-based tests detected both positive and purifying selection for both R-genes, as commonly found for animal immune genes. CONCLUSIONS: Our results highlight that combining fine and broad-scale sampling strategies can reveal the multiple factors influencing polymorphism and divergence at potentially adaptive genes such as R-genes

Restriction associated DNA-genotyping at multiple spatial scales in Arabidopsis lyrata reveals signatures of pathogen-mediated selection

Background: Genome scans based on outlier analyses have revolutionized detection of genes involved in adaptive processes, but reports of some forms of selection, such as balancing selection, are still limited. It is unclear whether high throughput genotyping approaches for identification of single nucleotide polymorphisms have sufficient power to detect modes of selection expected to result in reduced genetic differentiation among populations. In this study, we used Arabidopsis lyrata to investigate whether signatures of balancing selection can be detected based on genomic smoothing of Restriction Associated DNA sequencing (RAD-seq) data. We compared how different sampling approaches (both within and between subspecies) and different background levels of polymorphism (inbreeding or outcrossing populations) affected the ability to detect genomic regions showing key signatures of balancing selection, specifically elevated polymorphism, reduced differentiation and shifts towards intermediate allele frequencies. We then tested whether candidate genes associated with disease resistance (R-gene analogs) were detected more frequently in these regions compared to other regions of the genome. Results: We found that genomic regions showing elevated polymorphism contained a significantly higher density of R-gene analogs predicted to be under pathogen-mediated selection than regions of non-elevated polymorphism, and that many of these also showed evidence for an intermediate site-frequency spectrum based on Tajima’s D. However, we found few genomic regions that showed both elevated polymorphism and reduced FST among populations, despite strong background levels of genetic differentiation among populations. This suggests either insufficient power to detect the reduced population structure predicted for genes under balancing selection using sparsely distributed RAD markers, or that other forms of diversifying selection are more common for the R-gene analogs tested. Conclusions: Genome scans based on a small number of individuals sampled from a wide range of populations were sufficient to confirm the relative scarcity of signatures of balancing selection across the genome, but also identified new potential disease resistance candidates within genomic regions showing signatures of balancing selection that would be strong candidates for further sequencing efforts

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band