| 1. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 2. |
- Gibaud, Thomas, et al.
(författare)
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New routes to food gels and glasses
- 2012
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Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1364-5498 .- 1359-6640. ; 158, s. 267-284
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Tidskriftsartikel (refereegranskat)abstract
- We describe the possibility to create solid-like protein samples whose structural and mechanical properties can be varied and tailored over an extremely large range in a very controlled way through an arrested spinodal decomposition process. We use aqueous lysozyme solutions as a model globular protein system. A combination of video microscopy, small-angle neutron and X-ray scattering and reverse Monte Carlo modeling is used to characterize the structure of the bicontinuous network with two coexisting phases of a dilute protein solution and a glassy or arrested dense protein backbone at all relevant length scales. Rheological measurements are then used to determine the complex mechanical response of these protein gels as a function of protein concentration and quench temperature. While in particular the origin of the dependence of the mechanical properties on quench depth and concentration is not well understood currently, it seems ultimately connected to the particular bicontinuous structure of the arrested spinodal network created by the interplay between the early stage of a spinodal decomposition and the position of the glass line. We then generalize this behavior and discuss how this could open up new routes to prepare gel-like food systems with adjustable structural and mechanical properties. We present results from a first feasibility study where we use a depletion interaction caused by the addition of small non-adsorbing polymers to suspensions of casein micelles in order to create food gels with tunable structural and mechanical properties through an arrested spinodal decomposition process.
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| 3. |
- Voets, Ilja K., et al.
(författare)
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DMSO-Induced Denaturation of Hen Egg White Lysozyme
- 2010
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 114:36, s. 11875-11883
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Bazarian, Jeffrey J., et al.
(författare)
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Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI) : a multicentre observational study
- 2018
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Ingår i: Lancet Neurology. - : Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 17:9, s. 782-789
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.Methods: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.Findings: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.Interpretation: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.Funding: Banyan Biomarkers and US Army Medical Research and Materiel Command.
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| 6. |
- 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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| 7. |
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| 8. |
- Carlbring, Per, et al.
(författare)
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The effects of a 12-week relapse prevention program following acute depression treatment : A randomised controlled trial
- 2019
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Konferensbidrag (refereegranskat)abstract
- Context: Depression can be effectively treated using internet interventions. However, the relapse rate is non-ignorable. Methods: 286 participants were randomized to an additional relapse prevention program or a control group. Monthly telephone calls using the MINI diagnostic interview as well as online assessments were carried out for 24 months. Intervention: Standard cognitive behaviour therapy via the internet without guidance. Results: Relapse rates of 27.1% and 22.0% were reported in the relapse prevention program group and the control group respectively. A log-rank test of the Kaplan-Meier model did not show any significant difference between the prevention program group and the control group (χ2(1) = 0.87; p = .352) in terms of relapse rates. At the one-year follow-up, 79.2% in the prevention program group and 82.9% of the participants in the control group had PHQ-9 scores indicating them to be in remission. By the second-year follow-up the rate of remission was 75.8% in the relapse prevention program group and 81.2% in the control group. No significant differences could be seen neither at the one-year follow-up (χ2(1) = 0.36; p = .552) nor the two-year follow-up (χ2(1) = 0.53; p = .467). Conclusions: Don’t do it!
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| 9. |
- Carlbring, Per, et al.
(författare)
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The effects on depression of Internet-administered behavioral activation vs. physical exercise
- 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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| 10. |
- 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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