| 1. |
- Alosco, Michael L, et al.
(författare)
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Cerebrospinal fluid tau, Aβ, and sTREM2 in Former National Football League Players: Modeling the relationship between repetitive head impacts, microglial activation, and neurodegeneration.
- 2018
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:9, s. 1159-1170
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) protein analysis may facilitate detection and elucidate mechanisms of neurological consequences from repetitive head impacts (RHI), such as chronic traumatic encephalopathy. We examined CSF concentrations of total tau (t-tau), phosphorylated tau, and amyloid β1-42 and their association with RHI in former National Football League (NFL) players. The role of microglial activation (using sTREM2) was examined as a pathogenic mechanism of chronic traumatic encephalopathy.Sixty-eight former NFL players and 21 controls underwent lumbar puncture to quantify t-tau, p-tau181, amyloid β1-42, and sTREM2 in the CSF using immunoassays. The cumulative head impact index estimated RHI.No between-group differences for CSF analytes emerged. In the former NFL players, the cumulative head impact index predicted higher t-tau concentrations (P=.041), and higher sTREM2 levels were associated with higher t-tau concentrations (P=.009).In this sample of former NFL players, greater RHI and increased microglial activation were associated with higher CSF t-tau concentrations.
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| 2. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 3. |
- Brodtkorb, Thor-Henrik, 1976-
(författare)
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Cost-effectiveness analysis of health technologies when evidence is scarce
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Given the increasing pressures on health care budgets, economic evaluation is used in many countries to assist decision-making regarding the optimal use of competing health care technologies. Although the standard methods of estimating cost-effectiveness underpinning these decisions have gained widespread acceptance, concerns have been raised that many technologies would not be considered for funding, due to scarcity of evidence. However, as long as the amount and quality of evidence used for the analysis are properly characterized, scarce evidence per se should not be seen as a hindrance to perform cost-effectiveness analyses. Characterizing uncertainty appropriately, though, may pose a challenge even when there is a large body of evidence available, and even more so when evidence is scarce. The aims of this thesis are to apply a methodological framework of cost-effectiveness analysis and explore methods for characterising uncertainty when evidence is scarce. Three case studies associated with limited evidence provide economic evaluations on current decision problems, investigate the feasibility of using the framework, and explore methods for characterizing uncertainty when evidence is scarce.The results of the case studies showed that, given current information, providing transfemoral amputees with C-Leg and Airsonett Airshower to patients with perennial allergic asthma could be considered cost-effective whereas screening for hyperthrophic cardiomyopathy among young athletes is unlikely to be cost-effective. In the cases of C-Leg and Airsonett Airshower conducting further research is likely to be cost-effective. The case studies indicate that it is feasible to apply methods of cost-effectiveness in health care for technologies not commonly evaluated due to lack of evidence. The analysis showed that failing to account for individual experts’ might have a substantial effect on the interpretation of the results of cost-effectiveness analysis. Formal expert elicitation is a promising method of characterizing uncertainty when evidence is missing, and thus enable cost-effectiveness and value of further research to be appropriately estimated in such situations.In conclusion, this thesis shows that scarcity of evidence should not preclude the use of cost-effectiveness analysis. On the contrary, in such cases it is probably more important than ever to use a framework that enable us to define key parameters for a decision problem and identify available evidence in order to determine cost-effectiveness given current information and provide guidance on further data collection.
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| 4. |
- Crary, John F., et al.
(författare)
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Primary age-related tauopathy (PART) : a common pathology associated with human aging
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 755-766
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Tidskriftsartikel (refereegranskat)abstract
- We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A beta) plaques. For these "NFT+/A beta-aEuroe brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A beta accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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| 5. |
- Dewan, Ramita, et al.
(författare)
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Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
- 2021
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Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 109:3
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Tidskriftsartikel (refereegranskat)abstract
- We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
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| 6. |
- Frank, Brandon, et al.
(författare)
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Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.
- 2022
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:8, s. 1523-1536
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Tidskriftsartikel (refereegranskat)abstract
- We examined the ability of plasma hyperphosphorylated tau (p-tau)181 to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables.Plasma p-tau181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM.These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.
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| 7. |
- Klevjer, Thor A., et al.
(författare)
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In situ behaviour and acoustic properties of the deep living jellyfish Periphylla periphylla
- 2009
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Ingår i: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 31:8, s. 793-803
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Tidskriftsartikel (refereegranskat)abstract
- The importance of jellyfish in marine systems is increasingly being recognized, and in some ecosystems, jellyfish may now be considered the top predator. We studied the behaviour of individuals of the deep-water schypozoan Periphylla periphylla in one such location, the Lurefjord, Norway. The study was performed using a combination of submersible acoustics (38 kHz), video and net methods, and the focus was on variation in behaviour and vertical distribution in relation to the diel cycle. A proportion of the population underwent synchronous vertical migrations, but P. periphylla were still recorded throughout the water column both day and night. The majority of individuals were swimming (vertically) at speeds < 2 cm s(-1) irrespective of the time of day. However, occasional vertical swimming events with speeds exceeding 10 cm s(-1) were recorded. Such events of elevated vertical speeds were of short duration, followed by subsequent periods of no vertical movements. Different size fractions appeared to have different patterns of vertical swimming activity, with smaller jellyfish swimming more continuously than the larger Periphylla. The echo strengths of the individual returns (target strength, TS) peaked at approximately -62 dB, and variability in TS for individuals was high, with the strongest echoes seen in deep water. The results show the feasibility of acoustic methods for studying the in situ behaviour and acoustic properties of these jellyfish, but also that acoustically weak jellyfish are only recorded close to the transducer or the acoustic axis, which will bias acoustic data on vertical size distribution and acoustic abundance estimates.
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| 8. |
- Montoliu-Gaya, Laia, et al.
(författare)
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Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
- 2024
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Ingår i: Acta neuropathologica. - 1432-0533. ; 147:1
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Tidskriftsartikel (refereegranskat)abstract
- Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD=69, non-AD=54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC=89.8), p-tau231 (AUC=83.4), and p-tau205 (AUC=81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR<1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217=15.29, ORp-tau205=5.05 and ORp-tau231=3.86) and Braak staging (ORp-tau217=14.29, ORp-tau205=5.27 and ORp-tau231=4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.
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| 9. |
- Utne-Palm, Anne C., et al.
(författare)
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Trophic Structure and Community Stability in an Overfished Ecosystem
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5989, s. 333-336
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Tidskriftsartikel (refereegranskat)abstract
- Since the collapse of the pelagic fisheries off southwest Africa in the late 1960s, jellyfish biomass has increased and the structure of the Benguelan fish community has shifted, making the bearded goby (Sufflogobius bibarbatus) the new predominant prey species. Despite increased predation pressure and a harsh environment, the gobies are thriving. Here we show that physiological adaptations and antipredator and foraging behaviors underpin the success of these fish. In particular, body-tissue isotope signatures reveal that gobies consume jellyfish and sulphidic diatomaceous mud, transferring ""dead-end"" resources back into the food chain.
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| 10. |
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