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In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aβ1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.

This article uses Daniel José Older's Shadowshaper as the core of a unit challenging students and teachers to confront and dismantle systems of oppression.

Bariatric surgery is associated with weight loss attributed to reduced caloric intake, mechanical changes, and alterations in gut hormones. However, some studies have suggested a heightened incidence of colorectal cancer (CRC) has been associated with bariatric surgery, emphasizing the importance of identifying mechanisms of risk. The objective of this study was to determine if bariatric surgery is associated with decreases in fecal short-chain fatty acids (SCFA), a group of bacterial metabolites of fiber. Fecal samples (n = 22) were collected pre- (~6 weeks) and post-bariatric surgery (~4 months) in patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy. SCFA levels were quantified using liquid chromatography/mass spectrometry. Dietary intake was quantified using 24-h dietary recalls. Using an aggregate variable, straight SCFAs significantly decreased by 27% from pre- to post-surgery, specifically acetate, propionate, butyrate, and valerate. Pre-surgery weight was inversely associated with butyrate, with no association remaining post-surgery. Multiple food groups were positively (sugars, milk, and red and orange vegetables) and inversely (animal protein) associated with SCFA levels. Our results suggest a potential mechanism linking dietary intake and SCFA levels with CRC risk post-bariatric surgery with implications for interventions to increase SCFA levels.

How neural representations preserve information about multiple stimuli is mysterious. Because tuning of individual neurons is coarse (e.g., visual receptive field diameters can exceed perceptual resolution), the populations of neurons potentially responsive to each individual stimulus can overlap, raising the question of how information about each item might be segregated and preserved in the population. We recently reported evidence for a potential solution to this problem: when two stimuli were present, some neurons in the macaque visual cortical areas V1 and V4 exhibited fluctuating firing patterns, as if they responded to only one individual stimulus at a time (Jun et al., 2022). However, whether such an information encoding strategy is ubiquitous in the visual pathway and thus could constitute a general phenomenon remains unknown. Here, we provide new evidence that such fluctuating activity is also evoked by multiple stimuli in visual areas responsible for processing visual motion (middle temporal visual area, MT), and faces (middle fundus and anterolateral face patches in inferotemporal cortex - areas MF and AL), thus extending the scope of circumstances in which fluctuating activity is observed. Furthermore, consistent with our previous results in the early visual area V1, MT exhibits fluctuations between the representations of two stimuli when these form distinguishable objects but not when they fuse into one perceived object, suggesting that fluctuating activity patterns may underlie visual object formation. Taken together, these findings point toward an updated model of how the brain preserves sensory information about multiple stimuli for subsequent processing and behavioral action. [ABSTRACT FROM AUTHOR]

Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes.

Abstract Introduction Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature. Methods Community‐dwelling Mexican Americans and non‐Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository. Results Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non‐Hispanic Whites. Discussion The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations.

Abstract Background The current project sought to evaluate the impact that white matter hyperintensities (WMH) have on executive function in cognitively normal Mexican Americans, an underserved population with onset and more rapid progression of dementia. Methods Data from 515 participants (360 female) enrolled in the Health and Aging Brain Study: Health Disparities project were analyzed. Participants underwent clinical evaluation, cognitive testing, and a brain MRI. Linear regression was used to predict the effect of total WMH volume on cognitive test scores. Age, sex, and education were entered as covariates. Results Regression analysis showed that WMH volume significantly predicted executive function. WMH also predicted global cognition and attention scores, although not significantly after adjusting for age. Conclusion In this sample of cognitively normal Mexican Americans, we found that WMH volume was associated with lower scores in a measure of executive function, after accounting for age, sex, and education.

OBJECTIVES/GOALS: To determine the utility of any standard, one must first evaluate whether or not the standard meets the needs of the use case it is meant to support. We aim to quantify data availability of the HL7 FHIR standard to support data collection for three state-based registries in a rural state and measure the potential effects on data quality and collection time. METHODS/STUDY POPULATION: FHIR mapping will be performed to assess the level of HL7 FHIR standard completeness (or data element coverage) in supporting data collection for the three registries. A systematic approach, previously developed and used by Garza and Zozus, will be used to map registry data elements to corresponding HL7 FHIR standard resources. FHIR coverage will be calculated as a percentage (total data elements “Available in FHIR” vs. total data elements overall) and will be observed across different domain areas (i.e., demographics vs. medications vs. vital signs, etc.) in order to identify the domains with the least and most coverage. RESULTS/ANTICIPATED RESULTS: Although there have been informatics solutions that relied on data exchange standards to improve data collection, none have actually evaluated the coverage of the standard for supporting the needs of clinical data registries. To address this gap, we aim to evaluate the availability of the HL7 FHIR standard to support data collection for three state-based registries. These results will provide insight into the generalizability of a FHIR-based solution to support data acquisition and processing across multiple registries and demonstrate the potential for seamless exchange of that data for secondary use in clinical and translational research. Quantifying the coverage will also be used to further advance its development in order to meet the data collection needs of state and national clinical data registries. DISCUSSION/SIGNIFICANCE: Registries often rely on manual abstraction of EHR data. These manual approaches have had a negative impact on data quality and cost, often due to the complexities associated with collection and mapping of the data to fit the registry model. HL7 FHIR has the potential to address these issues by automating part or all of the data collection process.

Detection and location of the source of acoustic emission in a thin aluminum panel is demonstrated using a multichannel fiber laser sensor system. Acoustic emission generated by a crack in an aluminum panel used as a test coupon in an accelerated fatigue experiment is detected and the location of the crack identified. Acoustic emission is detected over a bandwidth of around 0.5 MHz from a serially multiplexed array of four laser sensors and compared with measurements taken from four piezo-electric sensors co-located with the fiber laser sensors. The location of the crack is determined by first estimating time difference of arrival of signals at each sensor using a novel algorithm based on the cumulative distribution transform method with hyperbolic positioning. The fiber laser sensor is shown to match the signal-to-noise ratio of the industry standard (Mistras S9225) piezo-electric acoustic emission sensor.

White matter hyperintensities (WMHs) are brain white matter lesions that are hyperintense on fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans. Larger WMH volumes have been associated with Alzheimer’s disease (AD) and with cognitive decline. However, the relationship between WMH volumes and cross-sectional cognitive measures has been inconsistent. We hypothesize that this inconsistency may arise from 1) the presence of AD-specific neuropathology that may obscure any WMH effects on cognition, and 2) varying criteria for creating a WMH segmentation. Manual and automated programs are typically used to determine segmentation boundaries, but criteria for those boundaries can differ. It remains unclear whether WMH volumes are associated with cognitive deficits, and which segmentation criteria influence the relationships between WMH volumes and clinical outcomes.In a sample of 260 non-demented participants (ages 55–90, 141 males, 119 females) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we compared the performance of five WMH segmentation methods, by relating the WMH volumes derived using each method to both clinical diagnosis and composite measures of executive function and memory. To separate WMH effects on cognition from effects related to AD-specific processes, we performed analyses separately in people with and without abnormal cerebrospinal fluid amyloid levels.WMH volume estimates that excluded more diffuse, lower-intensity lesions were more strongly correlated with clinical diagnosis and cognitive performance, and only in those without abnormal amyloid levels. These findings may inform best practices for WMH segmentation, and suggest that AD neuropathology may mask WMH effects on clinical diagnosis and cognition.

Minicollagens from cnidarian nematocysts are attractive potential building blocks for the creation of strong, lightweight and tough polymeric materials with the potential for dynamic and reconfigurable crosslinking to modulate functionality. In this study, the Hydra magnipapillata minicollagen-1 isoform was recombinantly expressed in bacteria, and a high throughput purification protocol was developed to generate milligram levels of pure protein without column chromatography. The resulting minicollagen-1 preparation demonstrated spectral properties similar to those observed with collagen and polyproline sequences as well as the ability to self-assemble into oriented fibers and bundles. Photo-crosslinking with Ru(II)(bpy)32+ was used to create robust hydrogels that were analyzed by mechanical testing. Interestingly, the minicollagen-1 hydrogels could be dissolved with reducing agents, indicating that ruthenium-mediated photo-crosslinking was able to induce disulfide metathesis to create the hydrogels. Together, this work is an important first step in creating minicollagen-based materials whose properties can be manipulated through static and reconfigurable post-translational modifications.

Abstract Introduction T1‐ and T2‐weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1‐weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM‐hyper) volume from FLAIR and white matter hypointensity (WM‐hypo) volume from T1‐weighted images and compared their associations with age and cerebrospinal fluid (CSF) β‐amyloid and tau. Methods A total of 56 nondemented participants (68–94 years) were recruited and gave informed consent. All participants went through MR imaging on a GE 1.5T scanner and of these 47 underwent lumbar puncture for CSF analysis. WM‐hypo was calculated using FreeSurfer analysis of T1 FSPGR 3D, and WM‐hyper was calculated with the Lesion Segmentation Toolbox in the SPM software package using T2‐FLAIR. Results WM‐hyper and WM‐hypo were strongly correlated (r = .81; parameter estimate (p.e.): 1.53 ± 0.15; p

Eating behavior may be affected by dopamine synthesis capacity. In this study, 6-[(18)F]-fluoro-L-m-tyrosine (FMT) positron emission tomography (PET) uptake in striatal subregions was correlated with BMI (kg/m(2)) and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen (P = .05). These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

High energy electron precipitation from the Earth's radiation belts is important for loss from the radiation belts and atmospheric chemistry. We follow up investigations presented in Reidy et al. (2021, https://doi.org/10.1029/2020ja028410) where precipitating flux is calculated inside the field of view of the POES T0 detector using quasi‐linear theory and pitch angle diffusion coefficients (Dαα) from the British Antarctic Survey (BAS). These results showed good agreements at >30 keV for L* >5 on the dawnside but the flux were too low at higher energies. We have investigated the effect of changing parameters in the calculation of the precipitating flux to improve the results for the higher energies using comparisons of in situ flux and cold plasma measurements from GOES‐15 and RBSP. We find that the strength of the diffusion coefficients rather than the shape of the source spectrum has the biggest effect on the calculated precipitation. In particular we find decreasing the cold plasma density used in the calculation of Dαα increases the diffusion and hence the precipitation at the loss cone for the higher energies, improving our results. The method of calculating Dαα is also examined, comparing co‐located rather than averaged RBSP measurements. We find that the method itself has minimal effect but using RBSP derived Dαα improved our results over using Dαα calculated using the entire BAS wave data base; this is potentially due to better measurements of the cold plasma density from RBSP than the other spacecraft included in the BAS wave data base (e.g., THEMIS). Plain Language Summary: High energy particles trapped in the Earth's radiation belt can enter the atmosphere, known as particle precipitation, and collide with atmospheric particles, which can change the atmospheric chemistry. This input into our atmosphere is key to understanding the effects of space weather on our climate system variability but is difficult to quantify. Reidy et al. (2021, https://doi.org/10.1029/2020ja028410) calculated the precipitation that would be measured by a low‐Earth orbiting satellite using wave‐particle theory and diffusion coefficients from a radiation belt model. Diffusion coefficients describe the amount of diffusion of the trapped radiation belt particle population driven by different sources (e.g., chorus waves). Reidy et al. (2021, https://doi.org/10.1029/2020ja028410) found good agreement between the calculated and measured precipitation for lower energy particles but found there was something missing for the higher energies. This paper investigates the impact of changing certain parameters within the calculations, finding the cold plasma density to be key in improving the results at higher energies. Key Points: Decreasing the cold plasma density increases calculated electron precipitation at the higher energiesCalculated precipitation for a low Earth orbiting detector is weakly dependent on the source spectrumRBSP derived diffusion coefficients provide more diffusion for precipitating particles than those derived from a larger wave database [ABSTRACT FROM AUTHOR]

We calculate the amplitude-to-phase (AM-to-PM) noise conversion in a modified unitraveling carrier photodetector. We obtained two nulls as measured in the experiments, and we explain their origin. The nulls appear due to the transit time variation when the average photocurrent varies, and the transit time variation is due to the change of electron velocity when the average photocurrent varies. We also show that the AM-to-PM conversion coefficient depends only on the pulse energy and is independent of the pulse duration when the duration is less than 500 fs. When the pulse duration is larger than 500 fs, the nulls of the AM-to-PM conversion coefficient shift to larger average photocurrents. This shift occurs because the increase in that pulse duration leads to a decrease in the peak photocurrent. The AM-to-PM noise conversion coefficient changes as the repetition rate varies. However, the repetition rate does not change the AM-to-PM conversion coefficient as a function of input optical pulse energy. The repetition rate changes the average photocurrent. We propose a design that would in theory improve the performance of the device.

The purpose of this study was to determine whether white matter microstructure measured by diffusion magnetic resonance imaging (dMRI) provides independent information about baseline level or change in executive function (EF) or memory (MEM) in older adults with and without cognitive impairment. Longitudinal data was acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study from phases GO and 2 (2009–2015). ADNI participants included were diagnosed as cognitively normal (n = 46), early mild cognitive impairment (MCI) (n = 48), late MCI (n = 29), and dementia (n = 39) at baseline. We modeled the association between dMRI-based global white matter mean diffusivity (MD) and baseline level and change in EF and MEM composite scores, in models controlling for baseline bilateral hippocampal volume, regional cerebral FDG PET metabolism and global cerebral AV45 PET uptake. EF and MEM composite scores were measured at baseline, 6, 12, 24 and 36 months. In the baseline late MCI and dementia groups, greater global MD was associated with lesser baseline EF, but not EF change nor MEM baseline or change. As expected, lesser hippocampal volume and lesser FDG PET metabolism was associated with greater rates of EF and MEM decline. In ADNI-GO/2 participants, white matter integrity provided independent information about current executive function, but was not sensitive to future cognitive change. Since individuals experiencing executive function declines progress to dementia more rapidly than those with only memory impairment, better biomarkers of future executive function decline are needed.