| 1. |
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| 2. |
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| 3. |
- van Doorn, Ljcv, et al.
(author)
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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
- 2017
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.
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| 4. |
- Amanullah, Rahman, et al.
(author)
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Spectra and Hubble Space Telescope Light Curves of Six Type Ia Supernovae at 0.511 < z < 1.12 and the Union2 Compilation
- 2010
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 716, s. 712-738
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Journal article (peer-reviewed)abstract
- We report on work to increase the number of well-measured Type Ia supernovae (SNe Ia) at high redshifts. Light curves, including high signal-to-noise Hubble Space Telescope data, and spectra of six SNe Ia that were discovered during 2001, are presented. Additionally, for the two SNe with z > 1, we present ground-based J-band photometry from Gemini and the Very Large Telescope. These are among the most distant SNe Ia for which ground-based near-IR observations have been obtained. We add these six SNe Ia together with other data sets that have recently become available in the literature to the Union compilation. We have made a number of refinements to the Union analysis chain, the most important ones being the refitting of all light curves with the SALT2 fitter and an improved handling of systematic errors. We call this new compilation, consisting of 557 SNe, the Union2 compilation. The flat concordance ΛCDM model remains an excellent fit to the Union2 data with the best-fit constant equation-of-state parameter w = -0.997+0.050 -0.054(stat)+0.077 -0.082(stat + sys together) for a flat universe, or w = -1.038+0.056 -0.059(stat)+0.093 -0.097(stat + sys together) with curvature. We also present improved constraints on w(z). While no significant change in w with redshift is detected, there is still considerable room for evolution in w. The strength of the constraints depends strongly on redshift. In particular, at z >~ 1, the existence and nature of dark energy are only weakly constrained by the data. Based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI). STScI is operated by the Association of Universities for Research in Astronomy (AURA), Inc. under the NASA contract NAS 5-26555. The observations are associated with programs HST-GO-08585 and HST-GO-09075. Based, in part, on observations obtained at the ESO La Silla Paranal Observatory (ESO programs 67.A-0361 and 169.A-0382). Based, in part, on observations obtained at the Cerro-Tololo Inter-American Observatory (CTIO), National Optical Astronomy Observatory (NOAO). Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT). Based, in part, on observations obtained at the Gemini Observatory (Gemini programs GN-2001A-SV-19 and GN-2002A-Q-31). Based, in part on observations obtained at the Subaru Telescope. Based, in part, on data that were obtained at the W. M. Keck Observatory.
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| 7. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 8. |
- Kruse, N., et al.
(author)
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Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study
- 2015
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 36:9, s. 2587-2596
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Journal article (peer-reviewed)abstract
- Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program -Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. (C) 2015 Elsevier Inc. All rights reserved.
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| 9. |
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| 13. |
- Frisoni, G. B., et al.
(author)
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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
- 2017
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In: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 16:8, s. 661-676
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Journal article (peer-reviewed)abstract
- The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
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| 14. |
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| 15. |
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| 16. |
- Nobili, Serena, et al.
(author)
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Constraining Dust and Color Variations of High-z SNe Using NICMOS on the Hubble Space Telescope
- 2009
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 700, s. 1415-1427
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Journal article (peer-reviewed)abstract
- We present data from the Supernova Cosmology Project for five high redshift Type Ia supernovae (SNe Ia) that were obtained using the NICMOS infrared camera on the Hubble Space Telescope. We add two SNe from this sample to a rest-frame I-band Hubble diagram, doubling the number of high redshift supernovae on this diagram. This I-band Hubble diagram is consistent with a flat universe (ΩM, ΩΛ) = (0.29, 0.71). A homogeneous distribution of large grain dust in the intergalactic medium (replenishing dust) is incompatible with the data and is excluded at the 5σ confidence level, if the SN host galaxy reddening is corrected assuming RV = 1.75. We use both optical and infrared observations to compare photometric properties of distant SNe Ia with those of nearby objects. We find generally good agreement with the expected color evolution for all SNe except the highest redshift SN in our sample (SN 1997ek at z = 0.863) which shows a peculiar color behavior. We also present spectra obtained from ground-based telescopes for type identification and determination of redshift. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute. STScI is operated by the association of Universities for Research in Astronomy, Inc. under the NASA contract NAS 5-26555. The observations are associated with program GO-07850.
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| 17. |
- Rubin, D., et al.
(author)
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Looking Beyond Lambda with the Union Supernova Compilation
- 2009
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 695, s. 391-403
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Journal article (peer-reviewed)abstract
- The recent robust and homogeneous analysis of the world's supernova distance-redshift data, together with cosmic microwave background and baryon acoustic oscillation data—provides a powerful tool for constraining cosmological models. Here we examine particular classes of scalar field, modified gravity, and phenomenological models to assess whether they are consistent with observations even when their behavior deviates from the cosmological constant Λ. Some models have tension with the data, while others survive only by approaching the cosmological constant, and a couple are statistically favored over Λ cold dark matter. Dark energy described by two equation-of-state parameters has considerable phase space to avoid Λ and next-generation data will be required to constrain such physics, with the level of complementarity between probes varying with cosmology.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Chetelat, G., et al.
(author)
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Amyloid-PET and 18-F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias
- 2020
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In: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:11, s. 951-962
-
Research review (peer-reviewed)abstract
- Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-18-fluorodeoxyglucose (F-18-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and F-18-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.
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| 26. |
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| 27. |
- Dongiovanni, P., et al.
(author)
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Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease
- 2015
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In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 61:2, s. 506-514
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Journal article (peer-reviewed)abstract
- Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P<0.05), had more-severe steatosis, necroinflammation, ballooning, and fibrosis (P<0.05), and were more likely to have NASH (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.23-2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20-3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25-0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P<0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39-0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver. (Hepatology 2015;61:506-514)
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| 28. |
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| 29. |
- Fischer-Posovszky, P, et al.
(author)
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Functional Significance and Predictive Value of MicroRNAs in Pediatric Obesity: Tiny Molecules with Huge Impact?
- 2016
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In: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 86:1, s. 3-10
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Journal article (peer-reviewed)abstract
- Obesity is a major health concern. While some children develop comorbidities such as insulin resistance and low-grade systemic inflammation upon weight gain, others stay metabolically healthy. There is an urgent need for clinically relevant markers with prognostic value related to disease development and intervention success. MicroRNAs (miRNAs) are established biomarkers for several disease states. Herein, we give a brief overview of miRNA biogenesis and function and the potential role of circulating miRNA in the context of pediatric obesity.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Inzaghi, E, et al.
(author)
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Insulin-Like Growth Factors and Metabolic Syndrome in Obese Children
- 2017
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In: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 87:6, s. 400-404
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Journal article (peer-reviewed)abstract
- <b><i>Background/Aims:</i></b> Insulin-like growth factor (IGF)-I is related to cardiometabolic risk in adults, whereas the metabolic role of IGF-II is unclear. The aim of this study was to assess IGFs in obese children and correlate them with metabolic syndrome (MetS) components. <b><i>Methods:</i></b> This is a retrospective study including 574 obese children (11.34 ± 3.16 years). All subjects underwent complete anthropometry and biochemical assessment. In a subgroup of 136 subjects, body composition was evaluated. IGF-I was measured in 300 obese subjects and IGF-II in 77 obese and 15 lean children. 177 subjects were divided according to the presence of 1 or more MetS criteria: group 1, subjects with 1 MetS criterion; group 2, subjects with 2 components; and group 3, subjects with MetS diagnosis. <b><i>Results:</i></b> IGF-I, IGF-II, and IGF-I/insulin-like growth factor-binding protein-3 ratio were not different among subjects with an increasing number of MetS criteria and were not associated with single components of MetS as well as with body composition parameters. In children younger than 10 years, IGF-I directly correlated with high-density lipoprotein cholesterol (<i>p</i> < 0.005) even after controlling for confounders. IGF-II was significantly higher in obese children and correlated with parameters of insulin sensitivity (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> IGFs were neither related to MetS nor to body composition parameters in obese children. Further studies are needed to clarify the mechanisms underlying the relationship between IGF-II and insulin sensitivity.
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| 35. |
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| 36. |
- Jacobs, Heidi I. L., et al.
(author)
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The association between white matter hyperintensities and executive decline in mild cognitive impairment is network dependent
- 2012
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In: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 33:1, s. 1-201
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Journal article (peer-reviewed)abstract
- White matter hyperintensities (WMH) in Mild Cognitive Impairment (MCI) have been associated with impaired executive functioning, although contradictory findings have been reported. The aim of this study was to examine whether WMH location influenced the relation between WMH and executive functioning in MCI participants (55-90 years) in the European multicenter memory-clinic-based DESCRIPA study, who underwent MRI scanning at baseline (N = 337). Linear mixed model analysis was performed to test the association between WMH damage in three networks (frontal-parietal, frontal-subcortical and frontal-parietal-subcortical network) and change in executive functioning over a 3-year period. WMH in the frontal-parietal and in the frontal-parietal-subcortical network were associated with decline in executive functioning. However, the frontal-subcortical network was not associated with change in executive functioning. Our results suggest that parietal WMH are a significant contributor to executive decline in MCI and that investigation of WMH in the cerebral networks supporting cognitive functions provide a new way to differentiate stable from cognitive declining MCI individuals. (C) 2012 Elsevier Inc. All rights reserved.
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| 37. |
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| 38. |
- Mazzali, P. A., et al.
(author)
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High-Velocity Features : A Ubiquitous Property of Type Ia Supernovae
- 2005
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 623, s. L37-L40
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Journal article (peer-reviewed)abstract
- Evidence of high-velocity features (HVFs) such as those seen in the near-maximum spectra of some Type Ia supernovae (SNe Ia; e.g., SN 2000cx) has been searched for in the available SN Ia spectra observed earlier than 1 week before B maximum. Recent observational efforts have doubled the number of SNe Ia with very early spectra. Remarkably, all SNe Ia with early data (seven in our Research Training Network sample and 10 from other programs) show signs of such features, to a greater or lesser degree, in Ca II IR and some also in the Si II λ6355 line. HVFs may be interpreted as abundance or density enhancements. Abundance enhancements would imply an outer region dominated by Si and Ca. Density enhancements may result from the sweeping up of circumstellar material (CSM) by the highest velocity SN ejecta. In this scenario, the high incidence of HVFs suggests that a thick disk and/or a high-density companion wind surrounds the exploding white dwarf, as may be the case in single degenerate systems. Large-scale angular fluctuations in the radial density and abundance distribution may also be responsible: this could originate in the explosion and would suggest a deflagration as the more likely explosion mechanism. CSM interaction and surface fluctuations may coexist, possibly leaving different signatures on the spectrum. In some SNe, the HVFs are narrowly confined in velocity, suggesting the ejection of blobs of burned material.
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| 39. |
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| 40. |
- Nobili, F, et al.
(author)
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Clinical utility and research frontiers of neuroimaging in movement disorders
- 2017
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In: The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... - 1827-1936. ; 61:4, s. 372-385
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Journal article (peer-reviewed)
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| 41. |
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| 42. |
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| 43. |
- Pagano, G., et al.
(author)
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Fanconi anaemia proteins : Major roles in cell protection against oxidative damage
- 2003
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In: Bioessays. - : Wiley. - 0265-9247 .- 1521-1878. ; 25:6, s. 589-595
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Research review (peer-reviewed)abstract
- Fanconi anaemia (FA) is a cancer-prone genetic disorder that is characterised by cytogenetic instability and redox abnormalities. Although rare subtypes of FA (B, D1 and D2) have been implicated in DNA repair through links with BRCA1 and BRCA2, such a role has yet to be demonstrated for gene products of the common subtypes. Instead, these products have been strongly implicated in xenobiotic metabolism and redox homeostasis through interactions of FANCC with cytochrome P-450 reductase and with glutathione S-transferase, and of FANCG with cytochrome P-450 2E1, as well as redox-dependent signalling through an interaction between FANCA and Akt kinase. We hypothesise that FA proteins act directly (via FANCC and FANCG) and indirectly (via FANCA, BRCA2 and FANCD2) with the machinery of cellular defence to modulate oxidative stress. The latter interactions may co-ordinate the link between the response to DNA damage and oxidative stress parameters (3, 6-12). © 2003 Wiley Periodicals, Inc.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Pelusi, S, et al.
(author)
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Prevalence and Risk Factors of Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Without Steatohepatitis.
- 2019
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In: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 17:11
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Journal article (peer-reviewed)abstract
- In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis.We analyzed data from 1738 subjects (44.9% with severe obesity) in a cross-sectional liver biopsy cohort enrolled at referral centers in Italy and Finland. Biopsy specimens were analyzed histologically by a blinded pathologist at each center, and a diagnosis of NASH was made based on steatosis (≥5% of hepatocytes), hepatocellular ballooning, and lobular inflammation. We also collected data on demographic features, metabolic comorbidities, and genetic factors, and performed logistic regression analyses. Findings were validated using data from 118 consecutive patients with NAFLD who underwent sequential liver biopsies at tertiary referral centers in Italy.In the cross-sectional cohort, 132 of 389 patients (33.9%) with significant fibrosis had no NASH and 39 patients (10.0%) had no inflammation. The dissociation between NASH and fibrosis was significantly greater in patients with severe obesity (P < .005). Steatosis, ballooning, and lobular inflammation each were associated independently with significant fibrosis (P < .001); age, adiposity, fasting hyperglycemia, and the PNPLA3 I148M variant also were associated with fibrosis. In patients without, but not in those with, NASH, significant fibrosis was associated with steatosis grade and the PNPLA3 I148M variant. In patients without NASH, age, fasting hyperglycemia, ballooning, and inflammation were associated with fibrosis. In the validation cohort, 16 of 47 patients (34.0%) with clinically significant fibrosis did not have NASH at baseline. In patients with fibrosis without baseline NASH, worsening of fibrosis (based on later biopsies) was associated with fasting hyperglycemia and more severe steatosis (P= .016).In an analysis of biopsy specimens collected from patients with NAFLD at a single time point, one third of patients with significant fibrosis did not have NASH. We validated this finding in a separate cohort. In patients without NASH, fasting hyperglycemia, severe steatosis, mild inflammation or ballooning, and the PNPLA3 I148M variant identified those at risk of significant fibrosis.
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| 48. |
- Ramenghi, U., et al.
(author)
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Diamond-Blackfan anaemia in the Italian population
- 1999
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 104:4, s. 841-8
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Journal article (peer-reviewed)abstract
- Diamond-Blackfan anaemia (DBA) is a congenital disease characterized by defective erythroid progenitor maturation: 30% of patients have congenital malformations. The link between these malformations and defective erythropoiesis is unclear: a defect in a molecule acting both on embryo development and haemopoiesis has been proposed. Inheritance is autosomal dominant in most familial cases, but recessive families have also been reported. Many cases are sporadic. A DBA locus has been mapped on chromosome 19q13.2 (Gustavsson et al, 1997), but several families unlinked to this locus have also been reported (Gustavsson et al, 1998). This paper presents clinical, epidemiological and molecular data for DBA in the Italian population. Segregation analysis of 19q markers in patients with DBA showed exclusion of this locus in 5/12 families with inherited DBA. There was evidently locus heterogeneity for DBA in this population. A new microdeletion was identified in one patient. Other families, in which DBA segregates concordantly with the 19q critical region, suggest incomplete penetrance and expressivity of the DBA gene.
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| 49. |
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| 50. |
- Stanishev, Vallery, et al.
(author)
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SN 2003du: 480 days in the life of a normal type Ia supernova
- 2007
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 469:2, s. 645-661
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Journal article (peer-reviewed)abstract
- Aims.We present a study of the optical and near-infrared (NIR) properties of the Type Ia Supernova (SN Ia) 2003du.Methods: An extensive set of optical and NIR photometry and low-resolution long-slit spectra was obtained using a number of facilities. The observations started 13 days before B-band maximum light and continued for 480 days with exceptionally good time sampling. The optical photometry was calibrated through the S-correction technique.Results: The {UBVRIJHK} light curves and the color indices of SN 2003du closely resemble those of normal SNe Ia. SN 2003du reached a B-band maximum of 13.49 ± 0.02 mag on JD2 452 766.38 ± 0.5. We derive a B-band stretch parameter of 0.988 ±0.003, which corresponds to Δ m15=1.02 ±0.05, indicative of a SN Ia of standard luminosity. The reddening in the host galaxy was estimated by three methods, and was consistently found to be negligible. Using an updated calibration of the V and {JHK} absolute magnitudes of SNe Ia, we find a distance modulus μ=32.79±0.15 mag to the host galaxy, UGC 9391. We measure a peak {uvoir} bolometric luminosity of 1.35(±0.20)×1043 erg s-1 and Arnett's rule implies that M56Ni≃0.68 ±0.14 Mȯ of 56Ni was synthesized during the explosion. Modeling of the {uvoir} bolometric light curve also indicates M56Ni in the range 0.6-0.8 Mȯ. The spectral evolution of SN 2003du at both optical and NIR wavelengths also closely resembles normal SNe Ia. In particular, the Si II ratio at maximum R(Si II) = 0.22 ±0.02 and the time evolution of the blueshift velocities of the absorption line minima are typical. The pre-maximum spectra of SN 2003du showed conspicuous high-velocity features in the Ca II H&K doublet and infrared triplet, and possibly in Si II λ6355, lines. We compare the time evolution of the profiles of these lines with other well-observed SNe Ia and we suggest that the peculiar pre-maximum evolution of Si II λ6355 line in many SNe Ia is due to the presence of two blended absorption components.
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