Summary Background TDP-43 is a major component of the ubiquitinated inclusions that characterise amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitin ...inclusions (FTLD-U). TDP-43 is an RNA-binding and DNA-binding protein that has many functions and is encoded by the TAR DNA-binding protein gene ( TARDBP ) on chromosome 1. Our aim was to investigate whether TARDBP is a candidate disease gene for familial ALS that is not associated with mutations in superoxide dismutase 1 ( SOD1 ). Methods TARDBP was sequenced in 259 patients with ALS, FTLD, or both. We used TaqMan-based SNP genotyping to screen for the identified variants in control groups matched to two kindreds of patients for age and ethnic origin. Additional clinical, genetic, and pathological assessments were made in these two families. Findings We identified two variants in TARDBP , which would encode Gly290Ala and Gly298Ser forms of TDP-43, in two kindreds with familial ALS. The variants seem to be pathogenic because they co-segregated with disease in both families, were absent in controls, and were associated with TDP-43 neuropathology in both members of one of these families for whom CNS tissue was available. Interpretation The Gly290Ala and Gly298Ser mutations are located in the glycine-rich domain of TDP-43, which regulates gene expression and mediates protein–protein interactions such as those with heterogeneous ribonucleoproteins. Owing to the varied and important cellular functions of TDP-43, these mutations might cause neurodegeneration through both gains and losses of function. The finding of pathogenic mutations in TARDBP implicates TDP-43 as an active mediator of neurodegeneration in TDP-43 proteinopathies, a class of disorder that includes ALS and FTLD-U. Funding National Institutes of Health (AG10124, AG17586, AG005136-22, PO1 AG14382), Department of Veterans Affairs, Friedrich-Baur Stiftung (0017/2007), US Public Health Service, ALS Association, and Fundació ‘la Caixa’.
To test the hypothesis that the atrophy rate measured from serial MRI studies is associated with time to subsequent clinical conversion to a more impaired state in both cognitively healthy elderly ...subjects and in subjects with amnestic mild cognitive impairment (MCI).
Ninety-one healthy elderly patients and 72 patients with amnestic MCI who met inclusion criteria were identified from the Mayo Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry. Atrophy rates of four different brain structures--hippocampus, entorhinal cortex, whole brain, and ventricle--were measured from a pair of MRI studies separated by 1 to 2 years. The time of the second scan marked the beginning of the clinical observation period.
During follow-up, 13 healthy patients converted to MCI or Alzheimer disease (AD), whereas 39 MCI subjects converted to AD. Among those healthy at baseline, only larger ventricular annual percent volume change (APC) was associated with a higher risk of conversion (hazard ratio for a 1-SD increase 1.9, p = 0.03). Among MCI subjects, both greater ventricular volume APC (hazard ratio for a 1-SD increase 1.7, p < 0.001) and greater whole brain APC (hazard ratio for a 1-SD increase 1.4, p = 0.007) increased the risk of conversion to AD. Both ventricular APC (hazard ratio for a 1-SD increase 1.59, p = 0.001) and whole brain APC (hazard ratio for a 1-SD increase 1.32, p = 0.009) provided additional predictive information to covariate-adjusted cross-sectional hippocampal volume at baseline about the risk of converting from MCI to AD.
Higher whole brain and ventricle atrophy rates 1 to 2 years before baseline are associated with an increased hazard of conversion to a more impaired state. Combining a measure of hippocampal volume at baseline with a measure of either whole brain or ventricle atrophy rates from serial MRI scans provides complimentary predictive information about the hazard of subsequent conversion from mild cognitive impairment to Alzheimer disease. However, overlap among those who did vs those who did not convert indicate that these measures are unlikely to provide absolute prognostic information for individual patients.
To correlate different methods of measuring rates of brain atrophy from serial MRI with corresponding clinical change in normal elderly subjects, patients with mild cognitive impairment (MCI), and ...patients with probable Alzheimer disease (AD).
One hundred sixty subjects were recruited from the Mayo Clinic Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry Studies. At baseline, 55 subjects were cognitively normal, 41 met criteria for MCI, and 64 met criteria for AD. Each subject underwent an MRI examination of the brain at the time of the baseline clinical assessment and then again at the time of a follow-up clinical assessment, 1 to 5 years later. The annualized changes in volume of four structures were measured from the serial MRI studies: hippocampus, entorhinal cortex, whole brain, and ventricle. Rates of change on several cognitive tests/rating scales were also assessed. Subjects who were classified as normal or MCI at baseline could either remain stable or convert to a lower-functioning group. AD subjects were dichotomized into slow vs fast progressors.
All four atrophy rates were greater among normal subjects who converted to MCI or AD than among those who remained stable, greater among MCI subjects who converted to AD than among those who remained stable, and greater among fast than slow AD progressors. In general, atrophy on MRI was detected more consistently than decline on specific cognitive tests/rating scales. With one exception, no differences were found among the four MRI rate measures in the strength of the correlation with clinical deterioration at different stages of the disease.
These data support the use of rates of change from serial MRI studies in addition to standard clinical/psychometric measures as surrogate markers of disease progression in AD. Estimated sample sizes required to power a therapeutic trial in MCI were an order of magnitude less for MRI than for change measures based on cognitive tests/rating scales.
The authors assessed whether measures of hippocampal water diffusivity at baseline can predict future progression to Alzheimer disease (AD) in amnestic mild cognitive impairment (aMCI). Higher ...baseline hippocampal diffusivity was associated with a greater risk of progression to AD in aMCI (p = 0.002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy.
The purpose of this study was to use serial imaging to gain insight into the sequence of pathologic events in Alzheimer's disease, and the clinical features associated with this sequence. We measured ...change in amyloid deposition over time using serial 11C Pittsburgh compound B (PIB) positron emission tomography and progression of neurodegeneration using serial structural magnetic resonance imaging. We studied 21 healthy cognitively normal subjects, 32 with amnestic mild cognitive impairment and 8 with Alzheimer's disease. Subjects were drawn from two sources—ongoing longitudinal registries at Mayo Clinic, and the Alzheimer's disease Neuroimaging Initiative (ADNI). All subjects underwent clinical assessments, MRI and PIB studies at two time points, approximately one year apart. PIB retention was quantified in global cortical to cerebellar ratio units and brain atrophy in units of cm3 by measuring ventricular expansion. The annual change in global PIB retention did not differ by clinical group (P = 0.90), and although small (median 0.042 ratio units/year overall) was greater than zero among all subjects (P < 0.001). Ventricular expansion rates differed by clinical group (P < 0.001) and increased in the following order: cognitively normal (1.3 cm3/year) < amnestic mild cognitive impairment (2.5 cm3/year) < Alzheimer's disease (7.7 cm3/year). Among all subjects there was no correlation between PIB change and concurrent change on CDR-SB (r = −0.01, P = 0.97) but some evidence of a weak correlation with MMSE (r =−0.22, P = 0.09). In contrast, greater rates of ventricular expansion were clearly correlated with worsening concurrent change on CDR-SB (r = 0.42, P < 0.01) and MMSE (r =−0.52, P < 0.01). Our data are consistent with a model of typical late onset Alzheimer's disease that has two main features: (i) dissociation between the rate of amyloid deposition and the rate of neurodegeneration late in life, with amyloid deposition proceeding at a constant slow rate while neurodegeneration accelerates and (ii) clinical symptoms are coupled to neurodegeneration not amyloid deposition. Significant plaque deposition occurs prior to clinical decline. The presence of brain amyloidosis alone is not sufficient to produce cognitive decline, rather, the neurodegenerative component of Alzheimer's disease pathology is the direct substrate of cognitive impairment and the rate of cognitive decline is driven by the rate of neurodegeneration. Neurodegeneration (atrophy on MRI) both precedes and parallels cognitive decline. This model implies a complimentary role for MRI and PIB imaging in Alzheimer's disease, with each reflecting one of the major pathologies, amyloid dysmetabolism and neurodegeneration.
Most noise reduction methods involve nonlinear processes, and objective evaluation of image quality can be challenging, since image noise cannot be fully characterized on the sole basis of the noise ...level at computed tomography (CT). Noise spatial correlation (or noise texture) is closely related to the detection and characterization of low-contrast objects and may be quantified by analyzing the noise power spectrum. High-contrast spatial resolution can be measured using the modulation transfer function and section sensitivity profile and is generally unaffected by noise reduction. Detectability of low-contrast lesions can be evaluated subjectively at varying dose levels using phantoms containing low-contrast objects. Clinical applications with inherent high-contrast abnormalities (eg, CT for renal calculi, CT enterography) permit larger dose reductions with denoising techniques. In low-contrast tasks such as detection of metastases in solid organs, dose reduction is substantially more limited by loss of lesion conspicuity due to loss of low-contrast spatial resolution and coarsening of noise texture. Existing noise reduction strategies for dose reduction have a substantial impact on lowering the radiation dose at CT. To preserve the diagnostic benefit of CT examination, thoughtful utilization of these strategies must be based on the inherent lesion-to-background contrast and the anatomy of interest. The authors provide an overview of existing noise reduction strategies for low-dose abdominopelvic CT, including analytic reconstruction, image and projection space denoising, and iterative reconstruction; review qualitative and quantitative tools for evaluating these strategies; and discuss the strengths and limitations of individual noise reduction methods.
This paper proposes the design of a 360° map establishment and real-time simultaneous localization and mapping (SLAM) algorithm based on equirectangular projection. All equirectangular projection ...images with an aspect ratio of 2:1 are supported for input image types of the proposed system, allowing an unlimited number and arrangement of cameras. Firstly, the proposed system uses dual back-to-back fisheye cameras to capture 360° images, followed by the adoption of the perspective transformation with any yaw degree given to shrink the feature extraction area in order to reduce the computational time, as well as retain the 360° field of view. Secondly, the oriented fast and rotated brief (ORB) feature points extracted from perspective images with a GPU acceleration are used for tracking, mapping, and camera pose estimation in the system. The 360° binary map supports the functions of saving, loading, and online updating to enhance the flexibility, convenience, and stability of the 360° system. The proposed system is also implemented on an nVidia Jetson TX2 embedded platform with 1% accumulated RMS error of 250 m. The average performance of the proposed system achieves 20 frames per second (FPS) in the case with a single-fisheye camera of resolution 1024 × 768, and the system performs panoramic stitching and blending under 1416 × 708 resolution from a dual-fisheye camera at the same time.
Hydrogen (H2) is pivotal to phasing out fossil fuel-based energy systems. It can be produced from different sources and using different technologies. Very few studies comprehensively discuss all ...available state-of-the-art technologies for H2 production, the challenges facing each process, and their economic feasibility and sustainability. The current study thus addresses these gaps to effectively direct future research towards improving H2 production techniques. Many conventional methods contribute to large greenhouse gas footprints, with high production costs and low efficiency. Steam methane reforming and coal gasification dominate the supply side of H2, due to their low production costs (<$3.50/kg). Water-splitting offers one of the most environmentally benign production methods when integrated with renewable energy sources. However, it is considerably expensive and ridden with the flaw of production of harmful by-products that affect efficiency. Fossil fuel processing technologies remain one of the most efficient forms of H2 production sources, with yields exceeding 80% and reaching up to 100%, with the lowest cost despite their high reliance on expensive catalysts. Whereas solar-driven power systems cost slightly less than $10 kg−1, coal gasification and steam reforming cost below $3.05 kg−1. Future research thus needs to be directed towards cost reduction of renewable energy-based H2 production systems, as well as in their decarbonization and designing more robust H2 storage systems that are compatible with long-distance distribution networks with adequate fuelling stations.
•H2 production technologies, their economic feasibility and sustainability are reviewed.•Low-cost steam methane reforming and coal gasification dominate the supply side of H2.•Water-splitting coupled with renewable sources offers one of the most eco-friendly methods.•Future research should focus on decarbonizing and lowering renewable H2 production cost.
We tested if rates of brain atrophy accelerate in individuals with amnestic mild cognitive impairment (aMCI) as they progress to typical late onset Alzheimer disease (AD). We included comparisons to ...subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN).
We studied 46 subjects with aMCI who progressed to AD (labeled aMCI-P), 46 CN, and 23 aMCI-S. All subjects must have had three or more serial MRI scans. Rates of brain shrinkage and ventricular expansion were measured across all available serial MRI scans in each subject. Change in volumes relative to the point at which subjects progressed to a clinical diagnosis of AD (the index date) was modeled in aMCI-P. Change in volumes relative to age was modeled in all three clinical groups.
In aMCI-P the change in pre to post index rate (i.e., acceleration) of ventricular expansion was 1.7 cm(3)/year, and acceleration in brain shrinkage was 5.3 cm(3)/year. Brain volume declined and ventricular volume increased in all three groups with age. Volume changes decelerated with increasing age in aMCI-P, and to a lesser extent in aMCI-S, but were linear in the matched CN. Among all subjects with aMCI, rates of atrophy were greater in apolipoprotein E epsilon 4 carriers than noncarriers.
Rates of atrophy accelerate as individuals progress from amnestic mild cognitive impairment (aMCI) to typical late onset Alzheimer disease (AD). Rates of atrophy are greater in younger than older subjects with aMCI who progressed to AD and subjects with aMCI who did not progress. We did not find that atrophy rates varied with age in 70- to 90-year-old cognitively normal subjects.
The excessive release of heavy metals into the environment is a major concern worldwide. Adsorption process is among the most effective techniques for heavy metals removal from waste streams and ...activated carbon has been widely used as an adsorbent. Therefore, this study was carried out to examine the potential and effectiveness of granular activated carbon (GAC) to remove heavy metals, particularly cadmium (Cd) and lead (Pb) through adsorption from the prepared solutions respectively. A fixed bed column test was conducted to simulate the actual condition of adsorption in a continuous manner in a filtration process. Different flow rates were used to evaluate their effects on the column performance where different breakthrough curves were obtained. The Adam-Bohart breakthrough curve equation was used to predict the breakthrough curve and to obtain the adsorption capacity of cadmium and lead on GAC. The results showed that the Adam-Bohart equation fitted the experimental data well and cadmium and lead can be successfully removed by granular activated carbon (GAC) through the column test.
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