| 1. |
- Prahalad, P., et al.
(författare)
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Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry
- 2022
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 23:2, s. 228-236
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Tidskriftsartikel (refereegranskat)abstract
- Aim: A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. Methods: Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18 months of diagnosis were included (similar to 10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, chi 2-tests were used to calculate differences between groups. Results: The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18 months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18 months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18 months of diagnosis. Conclusions: In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.
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| 2. |
- Gerhardsson, P., et al.
(författare)
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The SWEET Project 10-Year Benchmarking in 19 Countries Worldwide Is Associated with Improved HbA1c and Increased Use of Diabetes Technology in Youth with Type 1 Diabetes
- 2021
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The international SWEET registry (NCT04427189) was initiated in 2008 to improve outcomes in pediatric diabetes. A 10-year follow-up allowed studying time trends of key quality indicators in 22 centers from Europe, Australia, Canada, and India in youth with type 1 diabetes (T1D). Methods: Aggregated data per person with T1D <25 years of age were compared between 2008-2010 and 2016-2018. Hierarchic linear and logistic regression models were applied. Models were adjusted for gender, age-, and diabetes duration groups. Results: The first and second time periods included 4930 versus 13,654 persons, 51% versus 52% male, median age 11.3 [Q1; Q3: 7.9; 14.5] versus 13.3 [9.7; 16.4] years, and T1D duration 2.9 [0.8; 6.4] versus 4.2 [1.4; 7.7] years. The adjusted hemoglobin A1C (HbA1c) improved from 68 (95% confidence interval [CI]: 66-70) to 63 (60; 65) mmol/mol (P<0.0001) or 8.4 (95% CI: 8.2-8.6) to 7.9 (7.6; 8.1) % (P<0.0001). Across all age groups, HbA1c was significantly lower in pump and sensor users. Severe hypoglycemia declined from 3.8% (2.9; 5.0) to 2.4% (1.9; 3.1) (P<0.0001), whereas diabetic ketoacidosis events increased significantly with injection therapy only. Body mass index-standard deviation score also showed significant improvements 0.55 (0.46; 0.64) versus 0.42 (0.33; 0.51) (P<0.0001). Over time, the increase in pump use from 34% to 44% preceded the increase in HbA1c target achievement (<53mmol/mol) from 21% to 34%. Conclusions: Twice yearly benchmarking within the SWEET registry was associated with significantly improved HbA1c on a background of increasing pump and sensor use for 10 years in young persons with T1D.
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| 3. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 4. |
- Mezza, D., et al.
(författare)
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Characterization of the AGIPD1.1 readout chip and improvements with respect to AGIPD1.0
- 2019
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 945
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Tidskriftsartikel (refereegranskat)abstract
- AGIPD, the Adaptive Gain Integrating Pixel Detector, is a hybrid detector with a frame rate of 4.5 MHz, a dynamic range up to 104⋅ 12.4 keV photons, as well as single photon resolution, developed for the European XFEL (Eu.XFEL). The final 1 Mpixel detector system consists of 16 tiled modules each one with 16 readout chips. The single ASIC is 64 x 64 pixels, each with a size of 200 x 200 μm2. Each pixel can store up to 352 images. This work is focused on the characterization of AGIPD1.1, the second version of the full scale ASIC, and the improvements with respect to AGIPD1.0. From the measurements presented in this paper we show that the flaws observed in AGIPD1.0 (i.e. ghosting, crosstalk, slow readout speed) have been fixed in AGIPD1.1. In addition the main performance parameters such as noise, dynamic range and so on were measured for the new version of the ASIC and will be summarized.
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| 5. |
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| 6. |
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| 7. |
- Lee, M. R., et al.
(författare)
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Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study
- 2017
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 85, s. 14-19
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Tidskriftsartikel (refereegranskat)abstract
- Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r2=0.38; p=0.002) and drinks per week (r2=0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure. © 2017
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| 8. |
- Lindell, S. G., et al.
(författare)
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Intermittent Access to Ethanol Induces Escalated Alcohol Consumption in Primates
- 2017
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Ingår i: Journal of addictive behaviors, therapy and rehabilitation. - : SciTechnol. - 2324-9005. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process.
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| 9. |
- Suchankova, Petra, 1979, et al.
(författare)
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The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings
- 2017
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 52:4, s. 425-430
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Tidskriftsartikel (refereegranskat)abstract
- The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, beta = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, beta = -12.00, 95% CI = -19.10 to -4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration. Although preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted. We investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol.
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| 10. |
- Trunk, Ulrich, et al.
(författare)
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AGIPD : A multi megapixel, multi megahertz X-ray camera for the European XFEL
- 2017
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9781510611009
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Konferensbidrag (refereegranskat)abstract
- AGIPD is a hybrid pixel detector developed by DESY, PSI, and the Universities of Bonn and Hamburg. It is targeted for use at the European XFEL, a source with unique properties: a train of up to 2700 pulses is repeated at 10 Hz rate. The pulses inside a train are ≤100fs long and separated by 220 ns, containing up to 1012 photons of 12.4 keV each. The readout ASICs with 64 x 64 pixels each have to cope with these properties: Single photon sensitivity and a dynamic range up to 104 photons/pixel in the same image as well as storage for as many as possible images of a pulse train for delayed readout, prior to the next train. The high impinging photon flux also requires a very radiation hard design of sensor and ASIC, which uses 130 nm CMOS technology and radiation tolerant techniques. The signal path inside a pixel of the ASIC consists of a charge sensitive preamplifier with 3 individual gains, adaptively selected by a subsequent discriminator. The preamp also feeds to a correlated double sampling stage, which writes to an analogue memory to record 352 frames. It is random-access, so it can be used most efficiently by overwriting bad or empty images. Encoded gain information is stored to a similar memory. Readout of these memories is via a common charge sensitive amplifier in each pixel, and multiplexers on four differential ports. Operation of the ASIC is controlled via a command interface, using 3 LVDS lines. It also serves to configure the chip's operational parameters and timings.
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