The Montreal Cognitive Assessment (MoCA) is a common cognitive screener for detecting mild cognitive impairment (MCI). However, previously suggested cutoff scores of 26/30 and above is often ...criticized and lacks racial diversity. The purpose of this study is to investigate the potential influence of race on MoCA classification cutoff score accuracy.
Data were obtained from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set and yielded 4,758 total participants. Participants were predominately White (82.8%) and female (61.7%) with a mean age of 69.3 years (SD = 10.3) and education level of 16.3 years (SD = 2.6). Based on NACC's classification, participants were either cognitively normal (n = 3,650) or MCI (n = 1,108).
Sensitivity and specificity analyses revealed that when using the cutoff score of ≤26/30, the MoCA correctly classified 73.2% of White cognitively normal participants and 83.1% of White MCI participants. In contrast, this criterion correctly classified 40.5% of Black cognitively normal participants and 90.8% of Black MCI participants. Our sample was highly educated; therefore, we did not observe significant differences in scores when accounting for education across race. Classification statistics are presented.
Black participants were misclassified at a higher rate than White participants when applying the ≤26/30 cutoff score. We suggest cutoff scores of ≤25/30 be applied to White persons and ≤22/30 for Black persons. These findings highlight the need for racially stratified population-based norms given the high misclassification of Black participants without such adjustment.
The objective of this study was to advance analytical methods for detecting oil sands process-affected water (OSPW) seepage from mining containments and discriminating any such seepage from the ...natural bitumen background in groundwaters influenced by the Alberta McMurray formation. Improved sampling methods and quantitative analyses of two groups of monoaromatic acids were employed to analyze OSPW and bitumen-affected natural background groundwaters for source discrimination. Both groups of monoaromatic acids showed significant enrichment in OSPW, while ratios of O2/O4 containing heteroatomic ion classes of acid extractable organics (AEOs) did not exhibit diagnostic differences. Evaluating the monoaromatic acids to track a known plume of OSPW-affected groundwater confirmed their diagnostic abilities. A secondary objective was to assess anthropogenically derived artificial sweeteners and per- and polyfluoroalkyl substances (PFAS) as potential tracers for OSPW. Despite the discovery of acesulfame and PFAS in most OSPW samples, trace levels in groundwaters influenced by general anthropogenic activities preclude them as individual robust tracers. However, their inclusion with the other metrics employed in this study served to augment the tiered, weight of evidence methodology developed. This methodology was then used to confirm earlier findings of OSPW migrations into groundwater reaching the Athabasca River system adjacent to the reclaimed pond at Tar Island Dyke.
IceAct is a proposed surface array of compact (50 cm diameter) and cost-effective Imaging Air Cherenkov Telescopes installed at the site of the IceCube Neutrino Observatory at the geographic South ...Pole. Since January 2019, two IceAct telescope demonstrators, featuring 61 silicon pho- tomultiplier (SiPM) pixels have been taking data in the center of the IceTop surface array during the austral winter. We present the first analysis of hybrid cosmic ray events detected by the IceAct imaging air-Cherenkov telescopes in coincidence with the IceCube Neutrino Observatory, includ- ing the IceTop surface array and the IceCube in-ice array. By featuring an energy threshold of about 10 TeV and a wide field-of-view, the IceAct telescopes show promising capabilities of im- proving current cosmic ray composition studies: measuring the Cherenkov light emissions in the atmosphere adds new information about the shower development not accessible with the current detectors, enabling significantly better primary particle type discrimination on a statistical basis. The hybrid measurement also allows for detailed feasibility studies of detector cross-calibration and of cosmic ray veto capabilities for neutrino analyses. We present the performance of the telescopes, the results from the analysis of two years of data, and an outlook of a hybrid simulation for a future telescope array.
We present moderately deep (125 ks) {\it XMM-Newton} observations of supernova remnant G330.2\(+\)1.0. This remnant is one of only a few known that fall into "synchrotron-dominated" category, with ...the emission almost entirely dominated by a nonthermal continuum. Previous X-ray observations could only characterize the spectra of a few regions. Here, we examine the spectra from fourteen regions surrounding the entire rim, finding that the spectral properties of the nonthermal emission do not vary significantly in any systematic way from one part of the forward shock to another, unlike several other remnants of this class. We confirm earlier findings that the power-law index, \(\Gamma\), ranges from about 2.1-2.5, while the absorbing column density is generally between 2.0-2.6 \(\times 10^{22}\) cm\(^{-2}\). Fits with the {\it srcut} model find values of the roll-off frequency in the range of 10\(^{17.1} - 10^{17.5}\) Hz, implying energies of accelerated electrons of \(\sim 100\) TeV. These values imply a high shock velocity of \(\sim 4600\) km s\(^{-1}\), favoring a young age of the remnant. Diffuse emission from the interior is nonthermal in origin as well, and fits to these regions yield similar values to those along the rim, also implying a young age. Thermal emission is present in the east, and the spectrum is consistent with a \(\sim 650\) km s\(^{-1}\) shock wave encountering interstellar or circumstellar material with a density of \(\sim 1\) cm\(^{-3}\).
The supernova remnant (SNR) G150.3+4.5 was recently discovered in the radio band; it exhibits a shell-like morphology with an angular size of \(\sim 3^{\circ}\), suggesting either an old or a nearby ...SNR. Extended \(\gamma\)-ray emission spatially coincident with the SNR was reported in the Fermi Galactic Extended Source Catalog, with a power-law spectral index of \(\Gamma\) = 1.91 \(\pm\) 0.09. Studying particle acceleration in SNRs through their \(\gamma\)-ray emission is of primary concern to assess the nature of accelerated particles and the maximum energy they can reach. Using more than ten years of Fermi-LAT data, we investigate the morphological and spectral properties of the SNR G150.3+4.5 from 300 MeV to 3 TeV. We use the latest releases of the Fermi-LAT catalog, the instrument response functions and the Galactic and isotropic diffuse emissions. We use ROSAT all-sky survey data to assess any thermal and nonthermal X-ray emission, and we derive minimum and maximum distance to G150.3+4.5. We describe the \(\gamma\)-ray emission of G150.3+4.5 by an extended component which is found to be spatially coincident with the radio SNR. The spectrum is hard and the detection of photons up to hundreds of GeV points towards an emission from a dynamically young SNR. The lack of X-ray emission gives a tight constraint on the ambient density \(n_0 \leq 3.6 \times 10^{-3}\) cm\(^{-3}\). Since G150.3+4.5 is not reported as a historical SNR, we impose a lower limit on its age of \(t\) = 1 kyr. We estimate its distance to be between 0.7 and 4.5 kpc. We find that G150.3+4.5 is spectrally similar to other dynamically young and shell-type SNRs, such as RX J1713.7\(-\)3946 or Vela Junior. The broadband nonthermal emission is explained with a leptonic scenario, implying a downstream magnetic field of \(B = 5\) \(\mu\)G and acceleration of particles up to few TeV energies.
The standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American ...College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene‐specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC and determined 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewing functional assays. The rules were piloted on 81 variants and led to a change in classification in 40% of those that were classified in ClinVar, with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.
The objective of this study was to identify chemical components that could distinguish chemical mixtures in oil sands process-affected water (OSPW) that had potentially migrated to groundwater in the ...oil sands development area of northern Alberta, Canada. In the first part of the study, OSPW samples from two different tailings ponds and a broad range of natural groundwater samples were assessed with historically employed techniques as Level-1 analyses, including geochemistry, total concentrations of naphthenic acids (NAs) and synchronous fluorescence spectroscopy (SFS). While these analyses did not allow for reliable source differentiation, they did identify samples containing significant concentrations of oil sands acid-extractable organics (AEOs). In applying Level-2 profiling analyses using electrospray ionization high resolution mass spectrometry (ESI-HRMS) and comprehensive multidimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOF/MS) to samples containing appreciable AEO concentrations, differentiation of natural from OSPW sources was apparent through measurements of O2:O4 ion class ratios (ESI-HRMS) and diagnostic ions for two families of suspected monoaromatic acids (GC × GC-TOF/MS). The resemblance between the AEO profiles from OSPW and from 6 groundwater samples adjacent to two tailings ponds implies a common source, supporting the use of these complimentary analyses for source identification. These samples included two of upward flowing groundwater collected <1 m beneath the Athabasca River, suggesting OSPW-affected groundwater is reaching the river system.
The Kaposi's sarcoma‐associated herpes virus gene product K3 (KK3) subverts the MHC class I antigen presentation pathway by downregulating MHC class I from the plasma membrane. We now show that KK3 ...associates with MHC class I molecules and promotes ubiquitylation of class I after export from the endoplasmic reticulum. Ubiquitylation requires the KK3 N‐terminal plant homeodomain and provides the signal for class I internalization at the plasma membrane. Once internalized, ubiquitylated MHC class I is targeted to the late endocytic pathway, where it is degraded. Depletion by small interfering RNA of TSG101, a ubiquitin enzyme 2 variant protein involved in late endosomal sorting, prevents class I degradation and preserves cell surface class I expression in KK3‐expressing cells. These results suggest a mechanism by which the KK3‐induced class I ubiquitylation provides a signal for both internalization and sorting to the late endosomal pathway for degradation. KK3 is the first viral gene product that subverts the trafficking of a host protein via the ubiquitin‐dependent endosomal sorting machinery.
Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the ...melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.
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