| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 3. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 4. |
- Saxena, Richa, et al.
(författare)
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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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| 5. |
- Perez-Grijalba, V, et al.
(författare)
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Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
- 2019
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11:1, s. 96-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer’s disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. Both plasma Aβ42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers.MethodsWe included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification.ResultsEighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779–0.982). Discriminating performance of TP42/40 to detect Aβ-PET-positive subjects yielded sensitivity and specificity values at Youden’s cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aβ-PET scans by 64%. Combination of both FDG-PET scores and plasma Aβ biomarkers was found to be the most accurate Aβ-PET predictor, with an AUC of 0.965 (95% CI = 0.913–0.100).ConclusionsPlasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aβ positivity in preclinical and prodromal stages of Alzheimer’s disease.
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| 6. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 7. |
- Besson, H., et al.
(författare)
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A cross-sectional analysis of physical activity and obesity indicators in European participants of the EPIC-PANACEA study
- 2009
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 33:4, s. 497-506
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cross-sectional data suggest a strong association between low levels of physical activity and obesity. The EPIC-PANACEA ( European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project was designed to investigate the associations between physical activity and body mass index (BMI) and waist circumference based on individual data collected across nine European countries. Methods: In the European Prospective Investigation into Cancer and Nutrition ( EPIC), 519 931 volunteers were recruited between 1992 and 2000, of whom 405 819 had data on main variables of interest. Height, body weight and waist circumference were measured using standardized procedures. Physical activity was assessed using a validated four-category index reflecting a self-reported usual activity during work and leisure time. The associations between physical activity and BMI and waist circumference were estimated using multilevel mixed effects linear regression models, adjusted for age, total energy intake, smoking status, alcohol consumption and educational level. Results: A total of 125 629 men and 280 190 women with a mean age of 52.9 (s.d. 9.7) and 51.5 (s.d. 10.0) years, respectively were included. The mean BMI was 26.6 kg/m(2) (s.d. 3.6) in men and 25.0 kg/m(2) (s.d. 4.5) in women. Fifty percent of men and 30% of women were categorized as being active or moderately active. A one-category difference in the physical activity index was inversely associated with a difference of 0.18 kg/m(2) in the mean BMI (95% confidence interval, CI, 0.11, 0.24) and 1.04-cm (95% CI 0.82, 1.26) difference in waist circumference in men. The equivalent figures for women were 0.31 kg/m(2) (95% CI 0.23, 0.38) and 0.90 cm ( 95% CI 0.71, 1.08), respectively. Conclusions: Physical activity is inversely associated with both BMI and waist circumference across nine European countries. Although we cannot interpret the association causally, our results were observed in a large and diverse cohort independently from many potential confounders.
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| 8. |
- Perez-Grijalba, V, et al.
(författare)
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Plasma Aβ42/40 Ratio Detects Early Stages of Alzheimer's Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study
- 2019
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Ingår i: The journal of prevention of Alzheimer's disease. - : SERDI. - 2426-0266 .- 2274-5807. ; 6:1, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Background: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer’s disease (AD) in large population screening strategies. Objectives: This study evaluated the potential of plasma β-amyloid (Aβ) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. Design: Total plasma Aβ42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. Results: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). Conclusions: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.
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| 9. |
- Hasan, A, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
- 2012
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Ingår i: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
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Tidskriftsartikel (refereegranskat)abstract
- These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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| 10. |
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| 11. |
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| 12. |
- Munch, Marie W., et al.
(författare)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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| 13. |
- Andreasen, F M, et al.
(författare)
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Long-term survival of fragment bonding in the treatment of fractured crowns: a multicenter clinical study.
- 1995
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Ingår i: Quintessence international (Berlin, Germany : 1985). - 0033-6572. ; 26:10, s. 669-81
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Tidskriftsartikel (refereegranskat)abstract
- In three Scandinavian dental facilities, a series of 334 permanent incisors with fractures of the crown or crown and root was treated by reattachment of the fragment with a resin composite. Two centers (Oslo and Stockholm) employed acid etching of enamel alone for fragment bonding (n = 146), while the third center (Copenhagen) used a combination of enamel etching and dentinal bonding (n = 188). Although the final retention rate of fragment bonding was similar in the two groups, it took the dentinal bonding group almost three times as long to drop to 50% fragment retention. This difference could be attributed to greater bonding strength in the dentinal bonding group, greater risk of second injury in the younger acid-etching group, or difficulty in maintaining a dry operative field in the younger age group. The good fragment retention, acceptable esthetics, and pulpal vitality observed in the present series indicate that reattachment of the coronal fragment is a realistic alternative to placement of conventional resin-composite restorations.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Gilbert, M. Thomas P., et al.
(författare)
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Paleo-Eskimo mtDNA genome reveals matrilineal discontinuity in Greenland
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 320:5884, s. 1787-1789
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Tidskriftsartikel (refereegranskat)abstract
- The Paleo- Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New World's northern extremes. However, their origin and genetic relationship to later cultures are unknown. We sequenced a mitochondrial genome from a Paleo- Eskimo human by using 3400- to 4500- year- old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo- Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This result suggests that the earliest migrants into the New World's northern extremes derived from populations in the Bering Sea area and were not directly related to Native Americans or the later Neo- Eskimos that replaced them.
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| 19. |
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| 20. |
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| 21. |
- Mondejar, M. E., et al.
(författare)
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A review of the use of organic Rankine cycle power systems for maritime applications
- 2018
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Ingår i: Renewable and Sustainable Energy Reviews. - : Elsevier BV. - 1879-0690 .- 1364-0321. ; 91, s. 126-151
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Forskningsöversikt (refereegranskat)abstract
- Diesel engines are by far the most common means of propulsion aboard ships. It is estimated that around half of their fuel energy consumption is dissipated as low-grade heat. The organic Rankine cycle technology is a well-established solution for the energy conversion of thermal power from biomass combustion, geothermal reservoirs, and waste heat from industrial processes. However, its economic feasibility has not yet been demonstrated for marine applications. This paper aims at evaluating the potential of using organic Rankine cycle systems for waste heat recovery aboard ships. The suitable vessels and engine heat sources are identified by estimating the total recoverable energy. Different cycle architectures, working fluids, components, and control strategies are analyzed. The economic feasibility and integration on board are also evaluated. A number of research and development areas are identified in order to tackle the challenges limiting a widespread use of this technology in currently operating vessels and new-buildings. The results indicate that organic Rankine cycle units recovering heat from the exhaust gases of engines using low-sulfur fuels could yield fuel savings between 10% and 15%.
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| 22. |
- Rasmussen, Morten, et al.
(författare)
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Ancient human genome sequence of an extinct Palaeo-Eskimo
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 463:7282, s. 757-762
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Tidskriftsartikel (refereegranskat)abstract
- We report here the genome sequence of an ancient human. Obtained from ∼4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
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| 23. |
- Robertson, Agneta, 1954, et al.
(författare)
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Incidence of pulp necrosis subsequent to pulp canal obliteration from trauma of permanent incisors.
- 1996
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Ingår i: Journal of endodontics. - 0099-2399. ; 22:10, s. 557-60
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Tidskriftsartikel (refereegranskat)abstract
- Little long-term data are available on the frequency by which pulp canal obliteration (PCO) subsequent to trauma leads to pulp necrosis (PN). In this study, 82 concussed, subluxated, extruded, laterally luxated, and intruded permanent incisors presenting with PCO were followed for a period of 7 to 22 yr (mean 16 yr). At final clinical examination, 51% of the observed teeth responded normally to electric pulp testing (EPT). An additional 40% of the teeth although not responding to EPT were clinically and radiographically within normal limits. Yellow discoloration was a frequent finding. During the observation period, periapical bone lesions suggesting PN developed in seven teeth (8.5%). Twenty-yr pulp survival rate was 84%, as determined from life-table calculations. There was no higher frequency of PN in obliterated teeth subjected to caries, new trauma, orthodontic treatment, or complete crown coverage than intact teeth. Although the incidence of PN in teeth displaying PCO seems to increase over the course of time, prophylactic endodontic intervention on a routine basis does not seem justified.
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| 24. |
- Robertson, Agneta, 1954, et al.
(författare)
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Long-term prognosis of crown-fractured permanent incisors. The effect of stage of root development and associated luxation injury.
- 2000
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Ingår i: International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children. - 0960-7439. ; 10:3, s. 191-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the present study was to investigate pulp healing responses following crown fracture with and without pulp exposure as well as with and without associated luxation injury and in relation to stage of root development. PATIENT MATERIAL AND METHODS: The long-term prognosis was examined for 455 permanent teeth with crown fractures, 352 (246 with associated luxation injury) without pulpal involvement and 103 (69 with associated luxation injury) with pulp exposures. Initial treatment for all patients was provided by on-call oral surgeons at the emergency service, University Hospital (Rigshospitalet), Copenhagen. In fractures without pulpal involvement, dentin was covered by a hard-setting calcium hydroxide cement (Dycal), marginal enamel acid-etched (phosphoric acid gel), then covered with a temporary crown and bridge material. In the case of pulp exposure, pulp capping or partial pulpotomy was performed. Thereafter treatment was identical to the first group. Patients were then referred to their own dentist for resin composite restoration. RESULTS: Patients were monitored for normal pulp healing or healing complications for up to 17 years after injury (x = 2.3 years, range 0.2-17.0 years, SD + 2.7). Pulp healing was registered and classified into pulp survival with no radiographic change (PS), pulp canal obliteration (PCO) and pulp necrosis (PN). Healing was related to the following clinical factors: stage of root development at the time of injury, associated damage to the periodontium at time of injury (luxation) and time interval from injury until initial treatment. Crown fractures with or without pulp exposure and no concomitant luxation injury showed PS in 99%, PCO in 1% and PN in 0%. Crown fractures with concomitant luxation showed PS in 70%, PCO in 5% and PN in 25%. An associated damage to the periodontal ligament significantly increased the likelihood of pulp necrosis from 0% to 28% (P < 0.001) in teeth with only enamel and dentin exposure and from 0% to 14% (P < 0.001) in teeth with pulp exposure. CONCLUSIONS: In the case of concomitant luxation injuries, the stage of root development played an important role in the risk of pulp necrosis after crown fracture. However, the primary factor related to pulp healing events after crown fracture appears to be compromised pulp circulation due to concomitant luxation injuries.
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| 25. |
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| 26. |
- Andreasen, J. G., et al.
(författare)
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Multi-objective optimization of organic Rankine ycle power plants using pure and mixed working fluids
- 2015
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Ingår i: Proceedings of ASME ORC 2015. ; , s. 11-
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Konferensbidrag (refereegranskat)abstract
- For zeotropic mixtures, the temperature varies during phase change, which is opposed to the isothermalphase change of pure fluids. The use of such mixtures as working fluids in organic Rankine cyclepower plants enables a minimization of the mean temperature difference of the heat exchangers whenthe minimum pinch point temperature difference is kept fixed. A low mean temperature differencemeans low heat transfer irreversibilities, which is beneficial for cycle performance, but it also results inlarger heat transfer surface areas. Moreover, the two-phase heat transfer coefficients for zeotropic mixturesare usually degraded compared to an ideal mixture heat transfer coefficient linearly interpolatedbetween the pure fluid values. This entails a need for larger and more expensive heat exchangers. Previousstudies primarily focus on the thermodynamic benefits of zeotropic mixtures by employing firstand second law analyses. In order to assess the feasibility of using zeotropic mixtures, it is, however,important to consider the additional costs of the heat exchangers. In this study, we aim at evaluatingthe economic feasibility of zeotropic mixtures compared to pure fluids. We carry out a multi-objectiveoptimization of the net power output and the component costs for organic Rankine cycle power plantsusing low-temperature heat at 90 ◦C to produce electrical power at around 500 kW. The primary outcomesof the study are Pareto fronts, illustrating the power/cost relations for R32, R134a and R32/R134a(0.65/0.35mole). The results indicate that R32/134a is the best of these fluids, with 3.4 % higher net powerthan R32 at the same total cost of 1200 k$.
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| 27. |
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| 28. |
- Baldasso, Enrico, et al.
(författare)
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Technical and economic feasibility of organic Rankine cycle-based waste heat recovery systems on feeder ships: Impact of nitrogen oxides emission abatement technologies
- 2019
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Ingår i: Energy Conversion and Management. - : Elsevier BV. - 0196-8904. ; 183, s. 577-589
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Tidskriftsartikel (refereegranskat)abstract
- The International Maritime Organization recently revised the regulations concerning nitrogen and sulphur oxides emissions from commercial ships. In this context, it is important to investigate how emission abatement technologies capable of meeting the updated regulation on nitrogen oxides emissions affect the performance of waste heat recovery units to be installed on board new vessels. The objective of this paper is to assess the potential fuel savings of installing an organic Rankine cycle unit on board a hypothetical liquefied natural gas-fuelled feeder ship operating inside emission control areas. The vessel complies with the updated legislation on sulphur oxides emissions by using a dual fuel engine. Compliance with the nitrogen oxides emission regulation is reached by employing either a high or low-pressure selective catalytic reactor, or an exhaust gas recirculation unit. A multi-objective optimization was carried out where the objective functions were the organic Rankine cycle unit annual electricity production, the volume of the heat exchangers, and the net present value of the investment. The results indicate that the prospects for attaining a cost-effective installation of an organic Rankine unit are larger if the vessel is equipped with a low-pressure selective catalytic reactor or an exhaust gas recirculation unit. Moreover, the results suggest that the cost-effectiveness of the organic Rankine cycle units is highly affected by fuel price and the waste heat recovery boiler design constraints.
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| 30. |
- Faure, B., et al.
(författare)
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2D to 3D crossover of the magnetic properties in ordered arrays of iron oxide nanocrystals
- 2013
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 5:3, s. 953-960
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic 2D to 3D crossover behavior of well-ordered arrays of monodomain γ-Fe2O3 spherical nanoparticles with different thicknesses has been investigated by magnetometry and Monte Carlo (MC) simulations. Using the structural information of the arrays obtained from grazing incidence small-angle X-ray scattering and scanning electron microscopy together with the experimentally determined values for the saturation magnetization and magnetic anisotropy of the nanoparticles, we show that MC simulations can reproduce the thickness-dependent magnetic behavior. The magnetic dipolar particle interactions induce a ferromagnetic coupling that increases in strength with decreasing thickness of the array. The 2D to 3D transition in the magnetic properties is mainly driven by a change in the orientation of the magnetic vortex states with increasing thickness, becoming more isotropic as the thickness of the array increases. Magnetic anisotropy prevents long-range ferromagnetic order from being established at low temperature and the nanoparticle magnetic moments instead freeze along directions defined by the distribution of easy magnetization directions.
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| 31. |
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| 32. |
- Landen, Jaren W., et al.
(författare)
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Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study
- 2017
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Ingår i: Alzheimer's and Dementia: Translational Research and Clinical Interventions. - : Wiley. - 2352-8737. ; 3:3, s. 393-401
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected. Conclusions Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.
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| 33. |
- Schneider, L. S., et al.
(författare)
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Clinical trials and late-stage drug development for Alzheimer's disease : an appraisal from 1984 to 2014
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:3, s. 251-283
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Tidskriftsartikel (refereegranskat)abstract
- The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early-stage Alzheimer's disease trial samples using biomarkers and phase-specific outcomes. In conclusion, validated drug targets for Alzheimer's disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late-phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods.
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