612 research outputs found
High-Temperature, Low-Cycle Fatigue Behavior of Tantalum
High temperature, low cycle fatigue tests of tantalum in inert argon atmospher
Early anterior cingulate involvement is seen in presymptomatic MAPT P301L mutation carriers
BACKGROUND: PET imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic FTD but has not been explored in MAPT P301L mutation carriers. This study aimed to explore the patterns of presymptomatic hypometabolism and atrophy in MAPT P301L mutation carriers. METHODS: Eighteen asymptomatic members from five families with a P301L MAPT mutation were recruited to the study, six mutation carriers, and twelve mutation-negative controls. All participants underwent standard behavioural and cognitive assessment as well as [18F]FDG-PET and 3D T1-weighted MRI brain scans. Regional standardised uptake value ratios (SUVR) for the PET scan and volumes calculated from an automated segmentation for the MRI were obtained and compared between the mutation carrier and control groups. RESULTS: The mean (standard deviation) estimated years from symptom onset was 12.5 (3.6) in the mutation carrier group with a range of 7 to 18 years. No differences in cognition were seen between the groups, and all mutation carriers had a global CDR plus NACC FTLD of 0. Significant reduction in [18F] FDG uptake in the anterior cingulate was seen in mutation carriers (mean 1.25 [standard deviation 0.07]) compared to controls (1.36 [0.09]). A similar significant reduction was also seen in grey matter volume in the anterior cingulate in mutation carriers (0.60% [0.06%]) compared to controls (0.68% [0.08%]). No other group differences were seen in other regions. CONCLUSIONS: Anterior cingulate hypometabolism and atrophy are both apparent presymptomatically in a cohort of P301L MAPT mutation carriers. Such a specific marker may prove to be helpful in stratification of presymptomatic mutation carriers in future trials
Stepping into the Same River Twice: Field Evidence for the Repeatability of a CO2 Injection Test
A single well characterisation test was conducted at the CO2CRC Otway storage site in Victoria, Australia, in 2011 and repeated in 2014. The near-well permeability was found to have declined nearly 60% since the 2011 test, while the residual saturation inferred from a variety of techniques was lower in 2014. There was a significant change in water chemistry, suggesting an alteration of near-well reservoir properties. Possible reasons for these changes are explored, and the implications for other field tests are discussed
Comorbid amyloid-β pathology affects clinical and imaging features in VCD
INTRODUCTION: To date, the clinical relevance of comorbid amyloid-β (Aβ) pathology in patients with vascular cognitive disorders (VCD) is largely unknown. METHODS: We included 218 VCD patients with available cerebrospinal fluid Aβ42 levels. Patients were divided into Aβ+ mild-VCD (n = 84), Aβ- mild-VCD (n = 68), Aβ+ major-VCD (n = 31), and Aβ- major-VCD (n = 35). We measured depression with the Geriatric Depression Scale, cognition with a neuropsychological test battery and derived white matter hyperintensities (WMH) and gray matter atrophy from MRI. RESULTS: Aβ- patients showed more depressive symptoms than Aβ+. In the major-VCD group, Aβ- patients performed worse on attention (P = .02) and executive functioning (P = .008) than Aβ+. We found no cognitive differences in patients with mild VCD. In the mild-VCD group, Aβ- patients had more WMH than Aβ+ patients, whereas conversely, in the major-VCD group, Aβ+ patients had more WMH. Atrophy patterns did not differ between Aβ+ and Aβ- VCD group. DISCUSSION: Comorbid Aβ pathology affects the manifestation of VCD, but effects differ by severity of VCD
Mental State Inferences Abilities Contribution to Verbal Irony Comprehension in Older Adults with Mild Cognitive Impairment
Objective. The present study examined mentalizing capacities as well as the relative implication of mentalizing in the comprehension of ironic and sincere assertions among 30 older adults with mild cognitive impairment (MCI) and 30 healthy control (HC) subjects. Method. Subjects were administered a task evaluating mentalizing by means of short stories. A verbal irony comprehension task, in which participants had to identify ironic or sincere statements within short stories, was also administered; the design of the task allowed uniform implication of mentalizing across the conditions. Results. Findings indicated that participants with MCI have second-order mentalizing difficulties compared to HC subjects. Moreover, MCI participants were impaired compared to the HC group in identifying ironic or sincere stories, both requiring mental inference capacities. Conclusion. This study suggests that, in individuals with MCI, difficulties in the comprehension of ironic and sincere assertions are closely related to second-order mentalizing deficits. These findings support previous data suggesting a strong relationship between irony comprehension and mentalizing
Performance of Small Cluster Surveys and the Clustered LQAS Design to estimate Local-level Vaccination Coverage in Mali
<p>Abstract</p> <p>Background</p> <p>Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required.</p> <p>Methods</p> <p>We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A.</p> <p>Results</p> <p>VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans.</p> <p>Conclusions</p> <p>Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.</p
Determining residual CO(2) saturation through a dissolution test - Results from the CO2CRC Otway Project
Residual CO2 trapping (Sgr-CO2) is a key mechanism for geological CO2 storage. The CO2CRC undertook a sequence of field tests with the aim of comparing different ways of determining Sgr-CO2 including a dissolution test. Dissolution test results show an unexpectedly early breakthrough and low maximum CO2 concentrations in the back- produced water making the data inconclusive when using traditional data interpretation. Here, we consider two conditions to explain the observations: Firstly, residual CO2 is vertically unevenly distributed and, secondly, the fluid and residual CO2 are not in equilibrium. Furthermore, we postulate localised flow channels have formed during the 3- month test period caused by advective flow of CO2-saturated, low pH water leading to transport-controlled mineral dissolution.R.R. Haese, T. LaForce, C. Boreham, J. Ennis-King, B.M. Freifeld, L. Paterson, U. Schach
Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study
OBJECTIVE: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. METHODS: GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age. RESULTS: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98). CONCLUSIONS: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD
A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
Background
A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers.
Methods
A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest.
Results
When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN).
Conclusion
In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD
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