| 1. |
- Eriksson, Jan W., et al.
(författare)
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Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation : the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study
- 2008
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Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 52:6, s. 1030-1037
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P
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| 2. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 3. |
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| 4. |
- Carlbring, Per, et al.
(författare)
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Behavioral Activation vs. Physical Exercise in the Treatment of Mild to Moderate Depression
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Despite their potential as low-threshold, low-cost and high-flexibility treatments of depression, behavioral activation and physical exercise have not yet been directly compared. This study has examined the effects of these interventions, administered via the Internet. In this randomized controlled trial a total of 312 participants meeting the diagnostic criteria for mild to moderate major depression, recruited in multiple cycles and randomized to either a waiting list control group with delayed treatment, or one of the four active treatment groups: (1) physical exercise without a clear psychological treatment rationale; (2) physical exercise with a psychological treatment rationale; (3) behavioral activation a la Lewinsohn; or (4) behavioral activation a la Martel. A total of 72% were women and the average age of the participants were M=42.3 years (SD=13,5). More than half (53,9%) had a history of previous psychological treatment. Primary outcome measure was the 9-item Patient Health Questionnaire. Assessments were made on a weekly basis for the full duration of the acute treatment which was 12 weeks. The preliminary results are in line with previous online studies showing that all active treatment groups were superior to the waitlist (large effect sizes) and that only minor differences could be identified between the four active groups (large within effect sizes). At the time of the conference 6-month follow-up data will be available in addition to the already collected post-assessment data (analyzed according to the intention-to-treat principle).
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| 5. |
- Carlbring, Per, et al.
(författare)
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The effects on depression of Internet-administered behavioural activation and physical exercise with treatment rationale and relapse prevention : study protocol for a randomised controlled trial
- 2013
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14, s. 35-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite their potential as low-threshold, low-cost and high-flexibility treatments of depression, behavioural activation and physical exercise have not yet been directly compared. This study will examine the effects of these interventions, administered via the Internet. The added effect of providing a treatment rationale will also be studied, as well as a relapse prevention program featuring cognitive behavioural therapy components.Methods/Design: This randomised controlled trial will include 500 participants meeting the diagnostic criteria for major depression, recruited in multiple cycles and randomised to either a waiting list control group with delayed treatment, or one of the four treatment groups: (1) physical exercise without a clear treatment rationale; (2) physical exercise with treatment rationale; (3) behavioural activation with treatment rationale; or (4) behavioural activation without a clear treatment rationale. Post treatment, half of the participants will be offered a relapse prevention program. Primary outcome measure will be the Patient Health Questionnaire 9-item. Secondary measures include diagnostic criteria for depression, as well as self-reported anxiety, physical activity and quality of life. Measurements - done via telephone and the Internet - will be collected pre-treatment, weekly during treatment period, immediately post treatment and then monthly during a 24-month follow-up period.Discussion: The results of this study will constitute an important contribution to the body of knowledge of the respective interventions. Limitations are discussed.
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| 6. |
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| 7. |
- Jerdén, Lars, et al.
(författare)
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Personal health documents in school health education : A feasibility study
- 2007
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 35:6, s. 662-665
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine the feasibility of a school intervention using a personal health document adapted for adolescents. Methods: The health document was developed in close cooperation with groups of adolescents and tested among seventh-grade students at two junior high schools (n=339). The document was presented to the students by their regular teachers. For evaluation, an adolescent questionnaire was used at baseline and after one year. Results: After one year, 87% of adolescents reported having written in the health document, and 77% reported having had classes with discussions on subjects in the document. The health document was perceived as useful by 35% of the adolescents. Factors significantly related to personal usefulness were being born outside Sweden, experiencing fair treatment by teachers, being a nonsmoker, and having a positive school experience. Conclusions: Implementation of a personal health document in junior high-school health education was feasible and well accepted.
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| 8. |
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| 9. |
- Strøm, Michael, et al.
(författare)
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Assessment of EVAR Competence : Validity of a Novel Rating Scale (EVARATE) in a Simulated Setting
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 56:1, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aims of this study were to investigate the validity evidence for a novel procedure specific assessment tool of competence in endovascular aortic repair (EVAR) and to establish a pass/fail level for the assessment. Methods: Computed tomography angiography data of a 55 mm in diameter infrarenal aortic aneurysm was implemented into an endovascular simulator. Twenty-three physicians with varying EVAR experiences were video-recorded when performing a standard EVAR procedure on the simulator. Two experienced EVAR operators assessed the participants using the novel rating scale, “EndoVascular Aortic Repair Assessment of Technical Expertise” (EVARATE). Validity was studied according to the framework endorsed by the American Educational Research Association. Results: The EVARATE scale had a high internal consistency (Cronbach's alpha =.90). The inter-rater reliability was acceptable (Intraclass Correlation Coefficient =.68, p =.005). Specific EVAR experience correlated significantly with the EVARATE score (Spearman's rho =.62, p =.002), but general endovascular experience did not. Consequence analysis showed that the EVARATE assessment could distinguish novices from intermediates (p <.01) and from experts (p <.001). A pass/fail score was determined using the contrasting groups’ method. Conclusion: This paper presents the initial validity evidence for a novel procedure specific assessment tool, EVARATE, for operator competence in endovascular aortic repair investigated in a simulated setting. The assessment tool can be used to provide structured formative feedback to trainees.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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The IceCube Neutrino Observatory : instrumentation and online systems
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221 .- 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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