| 1. |
- Amundsen, Ellen J., et al.
(författare)
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Estimating incidence of problem drug use using the Horwitz-Thompson estimator - A new approach applied to people who inject drugs in Oslo 1985-2008
- 2016
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Ingår i: International journal on drug policy. - : Elsevier BV. - 0955-3959 .- 1873-4758. ; 27, s. 36-42
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trend in the number of new problem drug users per year (incidence) is the most important measure for studying the diffusion of problem drug use. Due to sparse data sources and complicated statistical models, estimation of incidence of problem drug use is challenging. The aim of this study is to widen the palette of available methods and data types for estimating incidence of problem drug use over time, and for identifying the trends. Methods: This study presents a new method of incidence estimation, applied to people who inject drugs (PWID) in Oslo. The method took into account the transition between different phases of drug use progression - active use, temporary cessation, and permanent cessation. The Horwitz-Thompson estimator was applied. Data included 16 cross-sectional samples of problem drug users who reported their onset of injecting drug use. We explored variation in results for selected probable scenarios of parameter variation for disease progression, as well as the stability of the results based on fewer years of cross-sectional samples. Results: The method yielded incidence estimates of problem drug use, over time. When applied to people in Oslo who inject drugs, we found a significant reduction of incidence of 63% from 1985 to 2008. This downward trend was also present when the estimates were based on fewer surveys (five) and in the results of sensitivity analysis for likely scenarios of disease progression. Conclusion: This new method, which incorporates temporarily inactive problem drug users, may become a useful tool for estimating the incidence of problem drug use over time. The method may be less data intensive than other methods based on first entry to treatment and may be generalized to other groups of substance users. Further studies on drug use progression would improve the validity of the results.
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| 2. |
- Dahn, Hollis A., et al.
(författare)
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Benchmarking ultra-high molecular weight DNA preservation methods for long-read and long-range sequencing
- 2022
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies in vertebrate genomics require sampling from a broad range of tissue types, taxa, and localities. Recent advancements in long-read and long-range genome sequencing have made it possible to produce high-quality chromosome-level genome assemblies for almost any organism. However, adequate tissue preservation for the requisite ultra-high molecular weight DNA (uHMW DNA) remains a major challenge. Here we present a comparative study of preservation methods for field and laboratory tissue sampling, across vertebrate classes and different tissue types.Results: We find that storage temperature was the strongest predictor of uHMW fragment lengths. While immediate flash-freezing remains the sample preservation gold standard, samples preserved in 95% EtOH or 20-25% DMSO-EDTA showed little fragment length degradation when stored at 4 degrees C for 6 hours. Samples in 95% EtOH or 20-25% DMSO-EDTA kept at 4 degrees C for 1 week after dissection still yielded adequate amounts of uHMW DNA for most applications. Tissue type was a significant predictor of total DNA yield but not fragment length. Preservation solution had a smaller but significant influence on both fragment length and DNA yield.Conclusion: We provide sample preservation guidelines that ensure sufficient DNA integrity and amount required for use with long-read and long-range sequencing technologies across vertebrates. Our best practices generated the uHMW DNA needed for the high-quality reference genomes for phase 1 of the Vertebrate Genomes Project, whose ultimate mission is to generate chromosome-level reference genome assemblies of all similar to 70,000 extant vertebrate species.
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| 3. |
- Gusarova, Viktoria, et al.
(författare)
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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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| 4. |
- Hinkley, Sasha, et al.
(författare)
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The JWST Early Release Science Program for the Direct Imaging and Spectroscopy of Exoplanetary Systems
- 2022
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1039
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Tidskriftsartikel (refereegranskat)abstract
- The direct characterization of exoplanetary systems with high-contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximize the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55 hr Early Release Science Program that will utilize all four JWST instruments to extend the characterization of planetary-mass companions to ∼15 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative data sets that will enable a broad user base to effectively plan for general observing programs in future Cycles.
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| 5. |
- Kraus, Ludwig, et al.
(författare)
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Altersspezifische Trends des risikoreichen Alkoholkonsums in Deutschland : Parallele oder unterschiedliche Verläufe?
- 2021
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Ingår i: Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. - : Springer Science and Business Media LLC. - 1436-9990 .- 1437-1588. ; 64, s. 652-659
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAccording to Skog’s collectivity of drinking cultures theory, changes in alcohol consumption in all groups and strata of the population take place as parallel displacement in the distribution of consumption. The aims of the present paper are (1) to illustrate temporal trends in risky drinking and episodic heavy drinking by age and gender and (2) to examine whether the trends are parallel in all age groups (“collectivity”) or diverge between age groups (“polarisation”).MethodsThe data are based on nine surveys of the Epidemiological Survey of Addiction (ESA) between 1995 and 2018. Risky drinking was defined as daily consumption of more than 12 g (for women) or 24 g (for men) of pure alcohol and episodic heavy drinking as consumption of five or more glasses of alcohol (about 70 g pure alcohol) on at least one day in the past 30 days. Linear regressions were calculated separately for age groups (18–29, 30–39, 40–49, and 50–59 years) and gender to predict the temporal effect on risky drinking or episodic heavy drinking and to test trends for differences.ResultsThe temporal changes of risky drinking by age group show soft collectivity among men and polarisation among women. Trends in episodic heavy drinking indicate polarisation for both genders; while the prevalence increased in the youngest and oldest age groups, it decreased in all other age groups.DiscussionIn light of a general decrease, the increasing trends in risky drinking in specific groups indicate the need for strengthening behavioural prevention. For the positive development to continue and to avoid a trend reversal, public health measures such as alcohol tax increases and reductions of alcohol availability need to be intensified.
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| 7. |
- Sassi, Atfa, et al.
(författare)
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Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels
- 2014
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 133:5, s. 1410-U681
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. Objective: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. Methods: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. Results: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p. Glu340del and p. Leu83Ser). A third homozygous mutation (p. Asp502Tyr) and the p. Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. Conclusion: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.
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