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- Al Kharusi, S., et al.
(författare)
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SNEWS 2.0 : a next-generation supernova early warning system for multi-messenger astronomy
- 2021
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:3
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Forskningsöversikt (refereegranskat)abstract
- The next core-collapse supernova in the Milky Way or its satellites will represent a once-in-a-generation opportunity to obtain detailed information about the explosion of a star and provide significant scientific insight for a variety of fields because of the extreme conditions found within. Supernovae in our galaxy are not only rare on a human timescale but also happen at unscheduled times, so it is crucial to be ready and use all available instruments to capture all possible information from the event. The first indication of a potential stellar explosion will be the arrival of a bright burst of neutrinos. Its observation by multiple detectors worldwide can provide an early warning for the subsequent electromagnetic fireworks, as well as signal to other detectors with significant backgrounds so they can store their recent data. The supernova early warning system (SNEWS) has been operating as a simple coincidence between neutrino experiments in automated mode since 2005. In the current era of multi-messenger astronomy there are new opportunities for SNEWS to optimize sensitivity to science from the next galactic supernova beyond the simple early alert. This document is the product of a workshop in June 2019 towards design of SNEWS 2.0, an upgraded SNEWS with enhanced capabilities exploiting the unique advantages of prompt neutrino detection to maximize the science gained from such a valuable event.
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| 2. |
- Karpyak, V. M., et al.
(författare)
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Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate
- 2014
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4, s. e462-
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Tidskriftsartikel (refereegranskat)abstract
- Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P = 4.6 x 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P = 0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P = 0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow.
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| 7. |
- Meng, Weida, et al.
(författare)
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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 4367-4382
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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| 8. |
- Ho, Ada M-C, et al.
(författare)
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Correlations between sex-related hormones, alcohol dependence and alcohol craving
- 2019
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Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 197, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex-related differences in the susceptibility, progression, and treatment response in alcohol-dependent subjects have been repeatedly reported. In this study, we aimed to investigate the associations of the sex-related hormone/protein levels with alcohol dependence (AD) and alcohol craving in male and female subjects.Methods: Plasma sex-related hormones (estradiol, estrone, total testosterone, progesterone, follicle stimulated hormone [FSH], luteinizing hormone), and sex hormone binding globulin were measured by mass spectrometry or automated immunoassays from 44 recently-abstained subjects (29 males and 15 females; mean age = 45.9 ± 15.6) meeting DSM-IV-TR criteria for AD and 44 age-, sex- and race-matched non-AD controls. Conditional logistic regression was conducted to examine the association of sex-related hormone and protein levels with AD risk, accounting for matching variables. Their associations with alcohol craving scales (Penn Alcohol Craving Scale and Inventory of Drug-Taking Situations) were assessed in AD subjects.Results: Plasma FSH level was significantly higher in AD males (10.3 ± 9.8 IU/L) than control males (8.0 ± 15.9 IU/L; p = 0.005, pcorrected = 0.035). We also found a significant inverse correlation of FSH level with propensity to drink in negative emotional situations (Spearman’s rho=-.540; p = 0.021) and positive correlations between progesterone level and craving intensity (Spearman’s rho=.464; p = 0.020) and between total testosterone level and propensity to drink under temptations (adjusted for no-drinking days; β=6.496; p = 0.041) in AD males.Conclusions: These results suggest that FSH, progesterone, and testosterone levels may be associated with AD and alcohol craving in AD males. Future research is needed to replicate these findings and investigate the underlying biological mechanisms.
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| 9. |
- Karpyak, Victor M., et al.
(författare)
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Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states
- 2013
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 16:5, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p = 0.00079) and with negative craving (p = 0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p = 0.024) and alcohol dependence (p = 0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.
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| 10. |
- Preuss, Ulrich W., et al.
(författare)
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PDYN rs2281285 Variant Association with Drinking to Avoid Emotional or Somatic Discomfort
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e78688-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: One of the proposed psychobiological pathways of craving attributes the desire for drinking in the context of tension, discomfort or unpleasant emotions, to "negative'' (or "relief'') craving. The aim of this study was to replicate a previously reported association of the PDYN rs2281285 variant with negative craving using a different phenotyping approach. Methods: The TaqMan (R) Genotyping Assay was used to genotype the rs2281285 variant in 417 German alcohol-dependent subjects. The presence of negative/relief craving was assessed by asking if participants ever ingested alcohol to avoid unwanted emotional or somatic discomfort. Results: The minor allele of rs2281285 was associated with an increased risk of drinking to avoid/escape unwanted emotional or somatic events (OR = 2.29, 95% CI = 1.08-4.85, p = 0.0298). Discussion: Despite the use of a different phenotyping approach to the measurement of negative craving, our results confirm the association between negative craving and PDYN rs2281285. Genetic markers of negative craving may help to identify subgroups of alcohol-dependent individuals vulnerable to relapse in the context of negative emotions or somatic discomfort, leading to the development of specifically tailored treatment strategies.
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