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  • Mousis, O., et al. (author)
  • Scientific rationale for Saturn's in situ exploration
  • 2014
  • In: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 104, s. 29-47
  • Journal article (peer-reviewed)abstract
    • Remote sensing observations meet some limitations when used to study the bulk atmospheric composition of the giant planets of our solar system. A remarkable example of the superiority of in situ probe measurements is illustrated by the exploration of Jupiter, where key measurements such as the determination of the noble gases' abundances and the precise measurement of the helium mixing ratio have only been made available through in situ measurements by the Galileo probe. This paper describes the main scientific goals to be addressed by the future in situ exploration of Saturn placing the Galileo probe exploration of Jupiter in a broader context and before the future probe exploration of the more remote ice giants. In situ exploration of Saturn's atmosphere addresses two broad themes that are discussed throughout this paper: first, the formation history of our solar system and second, the processes at play in planetary atmospheres. In this context, we detail the reasons why measurements of Saturn's bulk elemental and isotopic composition would place important constraints on the volatile reservoirs in the protosolar nebula. We also show that the in situ measurement of CO (or any other disequilibrium species that is depleted by reaction with water) in Saturn's upper troposphere may help constraining its bulk O/H ratio. We compare predictions of Jupiter and Saturn's bulk compositions from different formation scenarios, and highlight the key measurements required to distinguish competing theories to shed light on giant planet formation as a common process in planetary systems with potential applications to most extrasolar systems. In situ measurements of Saturn's stratospheric and tropospheric dynamics, chemistry and cloud-forming processes will provide access to phenomena unreachable to remote sensing studies. Different mission architectures are envisaged, which would benefit from strong international collaborations, all based on an entry probe that would descend through Saturn's stratosphere and troposphere under parachute down to a minimum of 10 bar of atmospheric pressure. We finally discuss the science payload required on a Saturn probe to match the measurement requirements.
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  • Hashemi, N., et al. (author)
  • Feasibility of Myocardial Performance Index for Evaluation of Left Ventricular Function during Dobutamine Stress Echocardiography before and after Coronary Artery Bypass Grafting
  • 2014
  • In: Echocardiography. - : Wiley. - 0742-2822 .- 1540-8175. ; 31:8, s. 989-995
  • Journal article (peer-reviewed)abstract
    • Aims: Myocardial performance index (MPI) is a measure of combined systolic and diastolic myocardial function. In patients with coronary artery disease (CAD) an increase in MPI is consistent with myocardial dysfunction. The objectives of this study were to characterize the changes in MPI after coronary artery bypass graft (CABG) at rest and at peak dobutamine stress echocardiography (DSE). Methods and Results: Thirty-six patients diagnosed with CAD and accepted for CABG were studied by standard echocardiography and DSE 1 month prior and 3 month after CABG. The MPI was calculated using pulsed-wave tissue Doppler imaging (PW-TDI) of the left ventricular (LV) wall-motion velocity. At baseline, ejection fraction (EF; 42.7 ± 8%) and wall-motion score index (WMSI; 1.1 ± 0.2) were impaired at rest as well as at peak DSE (EF; 49.2 ± 9 and WMSI 1.4 ± 0.2). MPI was prolonged both at rest (0.61 ± 0.13) and at peak DSE (0.78 ± 0.16). After CABG, EF and WMSI did not improve at rest (43.7 ± 8% and 1.1 ± 0.2, respectively). On the other hand, MPI improved substantially both at rest (0.45 ± 0.08; P < 0.001) and at peak DSE (0.56 ± 0.1; P < 0.001). At peak DSE an improvement of EF (54.2 ± 9; P < 0.05) and WMSI (1.1 ± 0.16; P < 0.001) was seen as well. Conclusion: Myocardial performance index shows significant improvement after CABG in patients with CAD both at rest and peak DSE and appears to be a sensitive measure of myocardial function.
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  • Hedman, JE, et al. (author)
  • Eelpout (Zoarces viviparus) in marine environmental monitoring
  • 2011
  • In: MARINE POLLUTION BULLETIN. - 0025-326X. ; 62:10, s. 2015-2029
  • Research review (peer-reviewed)abstract
    • The implementation of the EU Marine Strategy Framework Directive necessitates the development of common criteria and methodological standards for marineenvironmentalmonitoring and assessment across Europe. Eelpout (Zoarcesviviparus) is proposed as a key indicator organism in the Baltic and North Sea regions. This benthic fish species is widely used in ecotoxicological studies and as a bioindicator of local pollution due to its stationary behavior. Eelpout is included in the environmentalmonitoring program of several Baltic States, covering both chemical and biological effects measurements, and samples have been archived in environmental specimen banks for >15 years. A method for evaluating the frequency of larval aberrations has been suggested as a standardized assessment tool. The large scientific knowledge-base and considerable experience of long-term chemical and biological effects monitoring and specimen banking, make eelpout a suitable species for the assessment of Good Environmental Status in the Baltic and North Seas.
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  • Small, K. S., et al. (author)
  • Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes
  • 2011
  • In: Nat Genet. ; 43:6, s. 561-4
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies have identified many genetic variants associated with complex traits. However, at only a minority of loci have the molecular mechanisms mediating these associations been characterized. In parallel, whereas cis regulatory patterns of gene expression have been extensively explored, the identification of trans regulatory effects in humans has attracted less attention. Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL are highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbor variants directly associated with metabolic phenotypes. This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits.
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  • Ahlqvist, Jan B, 1951-, et al. (author)
  • A randomized controlled trial on 2 simulation-based training methods in radiology : effects on radiologic technology student skill in assessing image quality.
  • 2013
  • In: Simulation in Healthcare. - 1559-2332 .- 1559-713X. ; 8:6, s. 382-387
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: A simulator for virtual radiographic examinations was developed. In the virtual environment, the user can perform and analyze radiographic examinations of patient models without the use of ionizing radiation. We investigated if this simulation technique could improve education of radiology technology students. We compared student performance in the assessment of radiographic image quality after training with a conventional manikin or with the virtual radiography simulator.METHODS: A randomized controlled experimental study involving 31 first-year radiology technology students was performed. It was organized in 4 phases as follows: (I) randomization to control or experimental group based on the results of an anatomy examination; (II) proficiency testing before training; (III) intervention (control group, exposure and analysis of radiographic images of the cervical spine of a manikin; experimental group, exposure and analysis of the cervical spine images in the virtual radiography simulator); and (IV) proficiency testing after training.RESULTS: The experimental group showed significantly higher scores after training compared with those before training (P < 0.01). A linear mixed-effect analysis revealed a significant difference between the control and experimental groups regarding proficiency change (P = 0.01).CONCLUSIONS: Virtual radiographic simulation is an effective tool for learning image quality assessment. Simulation can therefore be a valuable adjunct to traditional educational methods and reduce exposure to x-rays and tutoring time.
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  • Arridge, Christopher S., et al. (author)
  • Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
  • 2012
  • In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
  • Journal article (peer-reviewed)abstract
    • The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
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  • Bonnert, M., et al. (author)
  • Internet-delivered cognitive behavior therapy for adolescents with functional gastrointestinal disorders - An open trial
  • 2014
  • In: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 1:3, s. 141-148
  • Journal article (peer-reviewed)abstract
    • Functional gastrointestinal disorders (FGID), including irritable bowel syndrome, functional dyspepsia and functional abdominal pain, are common in adolescents and are associated with substantially decreased quality of life. Cognitive behavior therapy for children and adolescents with FGID is one of few treatments that have shown effect, but treatment access is limited. In adults with irritable bowel syndrome, exposure-based internet-delivered CBT (ICBT) leads to reduced symptoms and increased quality of life, but studies in children are lacking. This open pilot aimed to evaluate feasibility and the potential efficacy of an exposure-based ICBT-program for adolescents with pain-predominant FGID. Twenty-nine adolescents (age 13-17), with FGID were included. The ICBT-program lasted for 8. weeks with weekly online therapist support. The protocol for adolescents included exposure to abdominal symptoms, while the protocol for parents aimed at increasing parents' attention to adolescent healthy behaviors. Assessment points were baseline, post-treatment and 6-month follow-up. The primary outcome was the Gastrointestinal Symptoms Rating Scale-IBS (GSRS-IBS). Effect sizes were calculated using Cohen's d in an intent to treat analysis. GSRS-IBS improved significantly from baseline to post-treatment (mean difference 6.48; 95% CI [2.37-10.58]) and to follow-up (mean difference 7.82; 95% CI [3.43-12.21]), corresponding to moderate effect sizes (within-group Cohen's d= 0.50; 95% CI [0.16-0.84] and d= 0.63; 95% CI [0.24-1.02], respectively). Treatment adherence was high with 22 of 29 (76%) adolescents completing the entire treatment period. High adherence indicates acceptability of format and content, while symptomatic improvement suggests potential efficacy for this ICBT intervention in adolescents with FGID. © 2014.
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  • Courteille, O., et al. (author)
  • Mixed Virtual Reality Simulation -Taking Endoscopic Simulation One Step Further
  • 2011
  • In: Medicine Meets Virtual Reality 18. - : IOS Press. - 9781607507062 - 9781607507055 ; 163, s. 144-6
  • Conference paper (peer-reviewed)abstract
    • This pilot study aimed to assess medical students' appraisals of a "mixed" virtual reality simulation for endoscopic surgery (with a virtual patient case in addition to a virtual colonoscopy) as well as the impact of this simulation set-up on students' performance. Findings indicate that virtual patients can enhance contextualization of simulated endoscopy and thus facilitate an authentic learning environment, which is important in order to increase motivation.
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  • Glass, Daniel, et al. (author)
  • Gene expression changes with age in skin, adipose tissue, blood and brain.
  • 2013
  • In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.RESULTS: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.CONCLUSIONS: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.
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  • Hedman, Christina A, et al. (author)
  • Intraperitoneal insulin delivery to patients with type 1 diabetes results in higher serum IGF-I bioactivity than continuous subcutaneous insulin infusion
  • 2014
  • In: Clinical Endocrinology. - : Wiley-Blackwell. - 0300-0664 .- 1365-2265. ; 81:1, s. 58-62
  • Journal article (peer-reviewed)abstract
    • ObjectiveType 1 diabetes (T1D) is associated with low IGF-I and altered levels of IGF-binding proteins (IGFBPs) in plasma. This may be of importance for insulin sensitivity and the risk of developing diabetic complications. We hypothesized that IGF-I bioactivity is affected by the route of insulin administration and that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced effect than continuous subcutaneous insulin infusion (CSII).Design and methodsWe compared 10 patients with T1D on CIPII with 20 age- and sex-matched patients on CSII. Blood sampling was carried out 7–9 am after an overnight fast. All patients were C-peptide negative. IGF-I bioactivity was measured in vitro using a specific IGF-I kinase receptor activation (KIRA) assay. IGF-I was also measured by immunoassay together with IGF-II, IGFBP-1 and IGFBP-2.ResultsWhen compared with subcutaneous insulin, intraperitoneal insulin resulted in (CIPII vs CSII) higher IGF-I bioactivity (1·83 ± 0·76 vs 1·16 ± 0·24 μg/l; P = 0·02), IGF-I (120 ± 35 vs 81 ± 19 μg/l; P = 0·01) and IGF-II (1050 ± 136 vs 879 ± 110 μg/l; P = 0·02). By contrast, log-transformed IGFBP-1 was reduced (P = 0·013), whereas log-transformed IGFBP-2 was not different (P = 0·12). There was a positive correlation between IGF bioactivity and IGF-I (r = 0·69; P < 0·001) and an inverse correlation between IGF-I bioactivity and log10 IGFBP-1 (r = −0·68, P < 0·001).ConclusionThe in vitro IGF-I bioactivity was higher in patients treated with CIPII compared with CSII supporting the theory that the route of insulin administration is of importance for the activity of the IGF system. Intraperitoneal insulin administration may therefore be beneficial by correcting the alterations of the IGF system in T1D.
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  • Herrmann, A., et al. (author)
  • Analysis of the Mushroom Nephrotoxin Orellanine and Its Glucosides
  • 2012
  • In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 75:10, s. 1690-1696
  • Journal article (peer-reviewed)abstract
    • Orellanine is a nephrotoxin found in various Cortinaceae mushroom species. Unintentional consumption after these species were confused with edible mushrooms such as Cantharellus tubaeformis has caused several casualties. In this work, a quantitative HPLC-ESI-MS/MS method for total orellanine in Cortinarius rubellus, spiked blood plasma, and a mushroom stew prepared from C. tubaeformis with the addition of a single specimen of C. rubellus is presented. The existence of mono- and diglucosylated orellanine in C. rubellus was also proven, although quantitative analysis could not be obtained for the glucosides due to rapid hydrolyzation to orellanine in the extract. Extraction with 3 M HCl or water mainly yielded orellanine, while MeOH or acidified MeOH mainly extracted mono- and diglucosylated orellanine. The highest recovery of total orellanine was obtained with 3 M HCl, which was subsequently used for quantitative analysis. A C-18 HPLC column and low pH in the eluents retained all these toxins. Orellanine could be detected at a 4.9 ng/mL level in all extracts, which is well below the threshold for acute toxic effects. Additionally, the fragmentation pattern of orellanine upon electrospray MS/MS was probed. The method described is useful for two important applications. First, it allows quantitative analysis of processed food products that may be contaminated by orellanine from Cortinaceae mushrooms. Second, orellanine is currently being evaluated as a potential cure of metastatic renal cancer, and this work provides a method for monitoring orellanine at low concentrations within the therapeutic interval in blood serum.
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  • Kjellin, A., et al. (author)
  • Hybrid simulation : bringing motivation to the art of teamwork training in the operating room
  • 2014
  • In: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 103:4, s. 232-236
  • Journal article (peer-reviewed)abstract
    • Background and Aims: Crew resource management-based operating room team training will be an evident part of future surgical training. Hybrid simulation in the operating room enables the opportunity for trainees to perform higher fidelity training of technical and non-technical skills in a realistic context. We focus on situational motivation and self-efficacy, two important factors for optimal learning in light of a prototype course for teams of residents in surgery and anesthesiology and nurses. Material and Methods: Authentic operating room teams consisting of residents in anesthesia (n = 2), anesthesia nurses (n = 3), residents in surgery (n = 2), and scrub nurses (n = 6) were, during a one-day course, exposed to four different scenarios. Their situational motivation was self-assessed (ranging from 1 = does not correspond at all to 7 = corresponds exactly) immediately after training, and their self-efficacy (graded from 1 to 7) before and after training. Training was performed in a mock-up operating theater equipped with a hybrid patient simulator (SimMan 3G; Laerdal) and a laparoscopic simulator (Lap Mentor Express; Simbionix). The functionality of the systematic hybrid procedure simulation scenario was evaluated by an exit questionnaire (graded from 1 = disagree entirely to 5 = agree completely). Results and Conclusions: The trainees were mostly intrinsically motivated, engaged for their own sake, and had a rather great degree of self-determination toward the training situation. Self-efficacy among the team members improved significantly from 4 to 6 (median). Overall evaluation showed very good result with a median grading of 5. We conclude that hybrid simulation is feasible and has the possibility to train an authentic operating team in order to improve individual motivation and confidence.
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  • Kooner, Jaspal S, et al. (author)
  • Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
  • 2011
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:10
  • Journal article (peer-reviewed)abstract
    • We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.
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  • Kroll, Thomas, et al. (author)
  • Resonant Inelastic X-ray Scattering on Ferrous and Ferric bis-imidazole Porphyrin and Cytochrome c : Nature and Role of the Axial Methionine-Fe Bond
  • 2014
  • In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 136:52, s. 18087-18099
  • Journal article (peer-reviewed)abstract
    • Axial Cu–S(Met) bonds in electron transfer (ET) active sites are generally found to lower their reduction potentials. An axial S(Met) bond is also present in cytochrome c (cyt c) and is generally thought to increase the reduction potential. The highly covalent nature of the porphyrin environment in heme proteins precludes using many spectroscopic approaches to directly study the Fe site to experimentally quantify this bond. Alternatively, L-edge X-ray absorption spectroscopy (XAS) enables one to directly focus on the 3d-orbitals in a highly covalent environment and has previously been successfully applied to porphyrin model complexes. However, this technique cannot be extended to metalloproteins in solution. Here, we use metal K-edge XAS to obtain L-edge like data through 1s2p resonance inelastic X-ray scattering (RIXS). It has been applied here to a bis-imidazole porphyrin model complex and cyt c. The RIXS data on the model complex are directly correlated to L-edge XAS data to develop the complementary nature of these two spectroscopic methods. Comparison between the bis-imidazole model complex and cyt c in ferrous and ferric oxidation states show quantitative differences that reflect differences in axial ligand covalency. The data reveal an increased covalency for the S(Met) relative to N(His) axial ligand and a higher degree of covalency for the ferric states relative to the ferrous states. These results are reproduced by DFT calculations, which are used to evaluate the thermodynamics of the Fe–S(Met) bond and its dependence on redox state. These results provide insight into a number of previous chemical and physical results on cyt c.
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  • Lindquist, David, et al. (author)
  • Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer
  • 2014
  • In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 110:7, s. 1793-1800
  • Journal article (peer-reviewed)abstract
    • Background:The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer has increased rapidly during the past decades. HPV is typically associated with a favourable outcome; however, a need exists for new and more effective prognostic and predictive markers for this disease. Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumour suppressor protein that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers, including cervical cancer, where HPV is a key aetiological agent.Methods:The prognostic value of LRIG1 and LRIG2 immunoreactivity was investigated in tumour specimens from a Swedish cohort of patients with tonsillar and base of tongue oropharyngeal cancers, including 278 patients.Results:LRIG1 immunoreactivity correlated with disease-free survival and overall survival in univariate and multivariate analyses. Notably, patients with HPV-positive tumours with high LRIG1 staining intensity or a high percentage of LRIG1-positive cells showed a very good prognosis. Furthermore, LRIG1 expression correlated with HPV status, whereas LRIG2 expression inversely correlated with HPV status.Conclusions:Taken together, the results suggest that LRIG1 immunoreactivity could be a clinically important prognostic marker in HPV-associated oropharyngeal cancer.
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  • Ljótsson, B., et al. (author)
  • Provoking symptoms to relieve symptoms : A randomized controlled dismantling study of exposure therapy in irritable bowel syndrome
  • 2014
  • In: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 55:1, s. 27-39
  • Journal article (peer-reviewed)abstract
    • An internet-delivered cognitive behavioral treatment (ICBT) based on systematic exposure exercises has previously shown beneficial effects for patients with irritable bowel syndrome (IBS). Exposure exercises may be perceived as difficult for patients to perform because of the elicited short-term distress and clinicians may be reluctant to use these interventions. The aim of this study was to compare ICBT with the same protocol without systematic exposure (ICBT-WE) to assess if exposure had any incremental value. This randomized controlled dismantling study included 309 participants diagnosed with IBS. The treatment interventions lasted for 10 weeks and included online therapist contact. ICBT-WE comprised mindfulness, work with life values, acceptance, and encouraged reduced avoidance behaviors, while ICBT also included systematic exposure to IBS symptoms and related situations. Severity of IBS symptoms was measured with the Gastrointestinal Symptom Rating Scale-IBS version (GSRS-IBS). The between-group Cohen's don GSRS-IBS was 0.47(95% CI: 0.23-0.70) at post-treatment and 0.48 (95% CI: 0.20-0.76) at 6-month follow-up, favoring ICBT. We conclude that the systematic exposure included in the ICBT protocol has incremental effects over the other components in the protocol. This study provides evidence for the utility of exposure exercises in psychological treatments for IBS.
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  • Lundberg, Marcus, et al. (author)
  • Metal-ligand Covalency of Iron Complexes from High-Resolution Resonant Inelastic X-ray Scattering
  • 2013
  • In: Journal of the American Chemical Society. - Washington : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:45, s. 17121-17134
  • Journal article (peer-reviewed)abstract
    • Data from Kα resonant inelastic X-ray scattering (RIXS) have been used to extract electronic structure information, i.e., the covalency of metal–ligand bonds, for four iron complexes using an experimentally based theoretical model. Kα RIXS involves resonant 1s→3d excitation and detection of the 2p→1s (Kα) emission. This two-photon process reaches similar final states as single-photon L-edge (2p→3d) X-ray absorption spectroscopy (XAS), but involves only hard X-rays and can therefore be used to get high-resolution L-edge-like spectra for metal proteins, solution catalysts and their intermediates. To analyze the information content of Kα RIXS spectra, data have been collected for four characteristic σ-donor and π-back-donation complexes: ferrous tacn [FeII(tacn)2]Br2, ferrocyanide [FeII(CN)6]K4, ferric tacn [FeIII(tacn)2]Br3 and ferricyanide [FeIII(CN)6]K3. From these spectra metal–ligand covalencies can be extracted using a charge-transfer multiplet model, without previous information from the L-edge XAS experiment. A direct comparison of L-edge XAS and Kα RIXS spectra show that the latter reaches additional final states, e.g., when exciting into the eg (σ*) orbitals, and the splitting between final states of different symmetry provides an extra dimension that makes Kα RIXS a more sensitive probe of σ-bonding. Another key difference between L-edge XAS and Kα RIXS is the π-back-bonding features in ferro- and ferricyanide that are significantly more intense in L-edge XAS compared to Kα RIXS. This shows that two methods are complementary in assigning electronic structure. The Kα RIXS approach can thus be used as a stand-alone method, in combination with L-edge XAS for strongly covalent systems that are difficult to probe by UV/vis spectroscopy, or as an extension to conventional absorption spectroscopy for a wide range of transition metal enzymes and catalysts.
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  • Nilsson, Tore A., et al. (author)
  • Dental student skill retention eight months after simulator-supported training in oral radiology
  • 2011
  • In: Journal of dental education. - : American Dental Education Association. - 1930-7837. ; 75:5, s. 679-684
  • Journal article (peer-reviewed)abstract
    • The purpose of this project was to investigate the long-term effects on skill to interpret spatial information in radiographs after conventional and simulator-supported training. The study was a follow-up of a previously reported randomized experimental study. The original study population was comprised of fifty-seven dental students. Forty-five individuals agreed to participate in a follow-up study eight months after completion of the original study. During the time interval between completion of the previous study and the follow-up study, the participants underwent an examination in oral radiology and had theoretical and clinical training in other topics than oral radiology. Skill at interpreting spatial information in radiographs was assessed with a previously used test instrument. The test instrument was identical with the instrument used for baseline assessment in the original study. The results showed that the skill to interpret spatial relations in radiographs eight months after completion of simulator-supported training was significantly better (p=0.01) than before training. The conventional training showed almost the same pattern, but the difference was smaller and not statistically significant (p=0.11). It is concluded that simulator-supported training is a valuable adjunct to conventional educational methods in oral radiology.
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  • Parts, Leopold, et al. (author)
  • Extent, causes, and consequences of small RNA expression variation in human adipose tissue.
  • 2012
  • In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:5
  • Journal article (peer-reviewed)abstract
    • Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population.
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  • Schéle, Ingrid A., 1967-, et al. (author)
  • A model of psychosocial work environment, stress, and satisfaction among dental students in Sweden
  • 2012
  • In: Journal of Dental Education. - Washington : American dental education association. - 0022-0337 .- 1930-7837. ; 76:9, s. 1206-1217
  • Journal article (peer-reviewed)abstract
    • Dental students are often described as stressed. The stress has, among other things, been connected to stressors in their psychosocial environment and inconsistent feedback. The hypothesis of this study was that the psychosocial work environment in dental schools leads to stress and affects the satisfaction of dental students and that tolerance for ambiguity shields students from stress. A web-based survey was sent to the entire Swedish dental student population in clinical training (N=805); the response rate was 40 percent. Structural equation modeling used in the analyses contains four main constructs: psychosocial work environment, tolerance for ambiguity, perceived stress, and student satisfaction (χ2=267.437, d.f.=174, p<0.001, Normed χ2=1.537, RMSEA= 0.041, CFI=0.98). Psychosocial work environment influenced both perceived stress and satisfaction: it accounted for almost all of the explained variance in perceived stress for women, while about half of the variance for the men was explained by tolerance for ambiguity. This study concluded that about 40 percent of the total perceived stress of these female dental students was related to their psychosocial work environment. Tolerance for ambiguity shielded men but not women from stress. An improved psychosocial work environment in dental schools would decrease the stress of both male and female dental students.
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33.
  • Thompson, Patricia A., et al. (author)
  • Loss of LRIG1 Locus Increases Risk of Early and Late Relapse of Stage I/II Breast Cancer
  • 2014
  • In: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:11, s. 2928-2935
  • Journal article (peer-reviewed)abstract
    • Gains and losses at chromosome 3p12-21 are common in breast tumors and associated with patient outcomes. We hypothesized that the LRIG1 gene at 3p14.1, whose product functions in ErbB-family member degradation, is a critical tumor modifier at this locus. We analyzed 971 stage I/II breast tumors using Affymetrix Oncoscan molecular inversion probe arrays that include 12 probes located within LRIG1. Copy number results were validated against gene expression data available in the public database. By partitioning the LRIG1 probes nearest exon 12/13, we confirm a breakpoint in the gene and show that gains and losses in the subregions differ by tumor and patient characteristics including race/ethnicity. In analyses adjusted for known prognostic factors, loss of LRIG1 was independently associated with risk of any relapse (HR, 1.90; 95% CI, 1.32-2.73), relapse >= 5 years (HR, 2.39; 95% CI, 1.31-4.36), and death (HR, 1.55; 95% CI, 1.11-2.16). Analyses of copy number across chromosome 3, as well as expression data from pooled, publicly available datasets, corroborated the hypothesis of an elevated and persistent risk among cases with loss of or low LRIG1. We concluded that loss/low expression of LRIG1 is an independent risk factor for breast cancer metastasis and death in stage I/II patients. Increased hazard in patients with loss/low LRIG1 persists years after diagnosis, suggesting that LRIG1 is acting as a critical suppressor of tumor metastasis and is an early clinical indicator of risk for late recurrences in otherwise low-risk patients.
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