Associations of Binge Drinking With Vascular Brain Injury and Atrophy in Older American Indians: The Strong Heart Study

Objectives: American Indians (AIs) generally consume less alcohol than the US general population; however, the prevalence of alcohol use disorder is higher. This is the first large cohort study to examine binge drinking as a risk factor for vascular brain injury (VBI). Methods: We used linear and Poisson regression to examine the association of self-reported binge drinking with VBI, measured via magnetic resonance imaging (MRI), in 817 older AIs who participated in the Strong Heart and Cerebrovascular Disease and Its Consequences in American Indians studies. Results: Any binge drinking at multiple time-points was associated with increased sulcal (β = 0.360, 95% CI [0.079, 0.641]) and ventricle dilatation (β = 0.512, 95% CI [0.174, 0.850]) compared to no binge drinking. Discussion: These observed associations are consistent with previous findings. Identifying how binge drinking may contribute to VBI in older AIs may suggest modifiable health behaviors for neurological risk reduction and disease prevention.

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Multiple Sclerosis: MRI and Other Imaging Approaches in MS

10.1093/med/9780199937837.003.0082 ◽

2017 ◽

Author(s):

Martina Absinta ◽

Daniel S. Reich

Keyword(s):

Multiple Sclerosis ◽

Current Knowledge ◽

Imaging Techniques ◽

Future Research ◽

Multiple Time ◽

Resonance Imaging ◽

Lesion Development ◽

Diagnostic Role ◽

Magnetic Resonance Imaging Mri ◽

Multiple Time Points

Aside from its paramount diagnostic role, imaging techniques, particularly magnetic resonance imaging (MRI), provide unparalleled insights into multiple sclerosis (MS) by assessing the spatiotemporal dynamics of the associated inflammation and neurodegeneration. This dynamical view, predicated on interrogation of individuals with MS at multiple time points, is impossible with pathology. The chapter approaches MRI in MS from this perspective, describing features related to lesion development and location, as well as assessment of global and regional damage. It summarizes current knowledge, addresses the limitations of that knowledge, and suggests ways in which imaging can advance future research.

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Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study

Neuroepidemiology ◽

10.1159/000459624 ◽

2017 ◽

Vol 48 (1-2) ◽

pp. 39-47 ◽

Cited By ~ 4

Author(s):

Astrid M. Suchy-Dicey ◽

Dean K. Shibata ◽

Tara M. Madhyastha ◽

Thomas J. Grabowski ◽

W.T. Longstreth Jr. ◽

...

Keyword(s):

Brain Injury ◽

American Indians ◽

Hippocampal Volume ◽

Cortical Atrophy ◽

Total Brain Volume ◽

Strong Heart Study ◽

Technical Errors ◽

Heart Study ◽

Total Brain ◽

Cranial Mri

Background: The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians. Methods: Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0- to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing. Results: The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy. Conclusions: Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population.

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Estimating the effect of a scanner upgrade on measures of grey matter structure for longitudinal designs

10.1101/2020.08.28.271296 ◽

2020 ◽

Author(s):

Evelyn Medawar ◽

Ronja Thieleking ◽

Iryna Manuilova ◽

Maria Paerisch ◽

Arno Villringer ◽

...

Keyword(s):

Grey Matter ◽

Correction Method ◽

Multiple Time ◽

Imaging Data ◽

Brain Images ◽

The Difference ◽

Longitudinal Imaging ◽

Magnetic Resonance Imaging Mri ◽

Multiple Time Points

1AbstractLongitudinal imaging studies are crucial for advancing the understanding of brain development over the lifespan. Thus, more and more studies acquire imaging data at multiple time points or with long follow-up intervals. In these studies changes to magnetic resonance imaging (MRI) scanners often become inevitable which may decrease the reliability of the MRI assessments and introduce biases.We therefore investigated the difference between MRI scanners with subsequent versions (3 Tesla Siemens Verio vs. Skyra fit) on the cortical and subcortical measures of grey matter in 116 healthy, young adults using the well-established longitudinal FreeSurfer stream for T1-weighted brain images. We found excellent between-scanner reliability for cortical and subcortical measures of grey matter structure (intra-class correlation coefficient > 0.8). Yet, paired t-tests revealed statistically significant differences in at least 75% of the regions, with percent differences up to 5%, depending on the outcome measure. Offline correction for gradient distortions only slightly reduced these biases. Further, T1-imaging based quality measures systematically differed between scanners.We conclude that scanner upgrades during a longitudinal study introduce bias in measures of cortical and subcortical grey matter structure. Therefore, before upgrading a MRI scanner during an ongoing study, researchers should prepare to implement an appropriate correction method for these effects.

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Comparing Vascular Brain Injury and Stroke by Cranial Magnetic Resonance Imaging, Physician-Adjudication, and Self-Report: Data from the Strong Heart Study

Neuroepidemiology ◽

10.1159/000517804 ◽

2021 ◽

pp. 1-9

Author(s):

Astrid Suchy-Dicey ◽

Clemma Muller ◽

Dean Shibata ◽

Barbara V. Howard ◽

Shelley A. Cole ◽

...

Keyword(s):

Brain Injury ◽

American Indians ◽

Health Care Access ◽

Performance Metrics ◽

Cognitive Testing ◽

Self Report ◽

Stroke Event ◽

Vascular Events ◽

Strong Heart Study ◽

Heart Study

Background: Epidemiologic studies often use self-report as proxy for clinical history. However, whether self-report correctly identifies prevalence in minority populations with health disparities and poor health-care access is unknown. Furthermore, overlap of clinical vascular events with covert vascular brain injury (VBI), detected by imaging, is largely unexamined. Methods: The Strong Heart Study recruited American Indians from 3 regions, with surveillance and adjudication of stroke events from 1989 to 2013. In 2010–2013, all 817 survivors, aged 65–95 years, underwent brain imaging, neurological history interview, and cognitive testing. VBI was defined as imaged infarct or hemorrhage. Results: Adjudicated stroke was prevalent in 4% of participants and separately collected, self-reported stroke in 8%. Imaging-defined VBI was detected in 51% and not associated with any stroke event in 47%. Compared with adjudication, self-report had 76% sensitivity and 95% specificity. Participants with adjudicated or self-reported stroke had the poorest performance on cognitive testing; those with imaging-only (covert) VBI had intermediate performance. Conclusion: In this community-based cohort, self-report for prior stroke had good performance metrics. A majority of participants with VBI did not have overt, clinically recognized events but did have neurological or cognitive symptoms. Data collection methodology for studies in a resource-limited setting must balance practical limitations in costs, accuracy, feasibility, and research goals.

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Estimating the effect of a scanner upgrade on measures of grey matter structure for longitudinal designs

PLoS ONE ◽

10.1371/journal.pone.0239021 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0239021

Author(s):

Evelyn Medawar ◽

Ronja Thieleking ◽

Iryna Manuilova ◽

Maria Paerisch ◽

Arno Villringer ◽

...

Keyword(s):

Grey Matter ◽

Correction Method ◽

Multiple Time ◽

Imaging Data ◽

Brain Images ◽

The Difference ◽

Longitudinal Imaging ◽

Magnetic Resonance Imaging Mri ◽

Multiple Time Points

Longitudinal imaging studies are crucial for advancing the understanding of brain development over the lifespan. Thus, more and more studies acquire imaging data at multiple time points or with long follow-up intervals. In these studies changes to magnetic resonance imaging (MRI) scanners often become inevitable which may decrease the reliability of the MRI assessments and introduce biases. We therefore investigated the difference between MRI scanners with subsequent versions (3 Tesla Siemens Verio vs. Skyra) on the cortical and subcortical measures of grey matter in 116 healthy, young adults using the well-established longitudinal FreeSurfer stream for T1-weighted brain images. We found excellent between-scanner reliability for cortical and subcortical measures of grey matter structure (intra-class correlation coefficient > 0.8). Yet, paired t-tests revealed statistically significant differences in at least 67% of the regions, with percent differences around 2 to 4%, depending on the outcome measure. Offline correction for gradient distortions only slightly reduced these biases. Further, T1-imaging based quality measures reflecting gray-white matter contrast systematically differed between scanners. We conclude that scanner upgrades during a longitudinal study introduce bias in measures of cortical and subcortical grey matter structure. Therefore, before upgrading a MRI scanner during an ongoing study, researchers should prepare to implement an appropriate correction method for these effects.

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Physical activity levels among ovarian cancer survivors: a prospective longitudinal cohort study

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-002107 ◽

2021 ◽

pp. ijgc-2020-002107

Author(s):

Tamara Jones ◽

Carolina Sandler ◽

Dimitrios Vagenas ◽

Monika Janda ◽

Andreas Obermair ◽

...

Keyword(s):

Physical Activity ◽

Ovarian Cancer ◽

Stage Iv ◽

Multiple Time ◽

Activity Levels ◽

Prospective Longitudinal Study ◽

Physical Activity Advice ◽

Physical Activity Levels ◽

Multiple Time Points ◽

Prospective Longitudinal

ObjectivePhysical activity following cancer diagnosis is associated with improved outcomes, including potential survival benefits, yet physical activity levels among common cancer types tend to decrease following diagnosis and remain low. Physical activity levels following diagnosis of less common cancers, such as ovarian cancer, are less known. The objectives of this study were to describe physical activity levels and to explore characteristics associated with physical activity levels in women with ovarian cancer from pre-diagnosis to 2 years post-diagnosis.MethodsAs part of a prospective longitudinal study, physical activity levels of women with ovarian cancer were assessed at multiple time points between pre-diagnosis and 2 years post-diagnosis. Physical activity levels and change in physical activity were described using metabolic equivalent task hours and minutes per week, and categorically (sedentary, insufficiently, or sufficiently active). Generalized Estimating Equations were used to explore whether participant characteristics were related to physical activity levels.ResultsA total of 110 women with ovarian cancer with a median age of 62 years (range 33–88) at diagnosis were included. 53–57% of the women were sufficiently active post-diagnosis, although average physical activity levels for the cohort were below recommended levels throughout the 2-year follow-up period (120–142.5min/week). A decrease or no change in post-diagnosis physical activity was reported by 44–60% of women compared with pre-diagnosis physical activity levels. Women diagnosed with stage IV disease, those earning a lower income, those receiving chemotherapy, and those currently smoking or working were more likely to report lower physical activity levels and had increased odds of being insufficiently active or sedentary.ConclusionsInterventions providing patients with appropriate physical activity advice and support for behavior change could potentially improve physical activity levels and health outcomes.

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The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma

Nature Communications ◽

10.1038/s41467-020-20524-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Eileen M. Boyle ◽

Shayu Deshpande ◽

Ruslana Tytarenko ◽

Cody Ashby ◽

Yan Wang ◽

...

Keyword(s):

Tumour Suppressor Genes ◽

Multiple Time ◽

Clonal Structure ◽

Time To Progression ◽

Novel Mutations ◽

Evolutionary Patterns ◽

Risk Of Progression ◽

Multiple Time Points ◽

Smoldering Myeloma ◽

Copy Number Changes

AbstractSmoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5–8.1), p = 0.001). In an analysis of change in clonal structure over time we studied 53 samples from nine patients at multiple time points. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are key mechanisms underlying the transition to MM, which can precede progression and be used to guide early intervention strategies.

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Statistical Estimation of Accelerated Biological Brain Aging After Mild Traumatic Brain Injury in Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.3282 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 890-890

Author(s):

Andrei Irimia ◽

Jun Kim ◽

Shania Wang ◽

Hyung Jun Lee ◽

Van Ngo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Brain Aging ◽

Rate Of Change ◽

Time Period ◽

Weighted Magnetic Resonance Imaging ◽

Neurological Conditions ◽

Magnetic Resonance Imaging Mri ◽

Brain Age

Abstract Estimating biological brain age (BA) has the potential of identifying individuals at relatively high risk for accelerated neurodegeneration. This study compares the brain’s chronological age (CA) to its BA and reveals the BA rate of change after mild traumatic brain injury (mTBI) in an aging cohort. Using T1-weighted magnetic resonance imaging (MRI) volumes and cortical thickness, volume, surface area, and Gaussian curvature obtained using FreeSurfer software; we formulated a multivariate linear regression to determine the rate of BA increase associated with mTBI. 95 TBI patients (age in years (y): μ = 41 y, σ = 17 y; range = 18 to 83) were compared to 462 healthy controls (HCs) (age: μ = 69 y, σ = 18 y; range = 25 to 95) over a 6-month time period following mTBI. Across the initial ~6 months following injury, patients’ BAs increased by ~3.0 ± 1.2 years due to their mTBIs alone, i.e., above and beyond typical brain aging. The superior temporal and parahippocampal gyri, two structures involved in memory formation and retrieval, exhibited the fastest rates of TBI-related BA. In both hemispheres, the volume of the hippocampus decreased (left: μ=0.28%, σ=4.40%; right: μ=0.12%, σ=4.84%). These findings illustrate BA estimation techniques’ potential to identify TBI patients with accelerated neurodegeneration, whose rate is strongly associated with the risk for dementia and other aging-related neurological conditions.

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Use of TanDEM-X and SRTM-C Data for Detection of Deforestation Caused by Bark Beetle in Central European Mountains

Remote Sensing ◽

10.3390/rs13153042 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3042

Author(s):

Kateřina Gdulová ◽

Jana Marešová ◽

Vojtěch Barták ◽

Marta Szostak ◽

Jaroslav Červenka ◽

...

Keyword(s):

Bark Beetle ◽

Synergistic Effects ◽

Canopy Height ◽

Surface Model ◽

Multiple Time ◽

Central European ◽

Time Points ◽

Bohemian Forest ◽

Multiple Time Points ◽

Surrounding Areas

The availability of global digital elevation models (DEMs) from multiple time points allows their combination for analysing vegetation changes. The combination of models (e.g., SRTM and TanDEM-X) can contain errors, which can, due to their synergistic effects, yield incorrect results. We used a high-resolution LiDAR-derived digital surface model (DSM) to evaluate the accuracy of canopy height estimates of the aforementioned global DEMs. In addition, we subtracted SRTM and TanDEM-X data at 90 and 30 m resolutions, respectively, to detect deforestation caused by bark beetle disturbance and evaluated the associations of their difference with terrain characteristics. The study areas covered three Central European mountain ranges and their surrounding areas: Bohemian Forest, Erzgebirge, and Giant Mountains. We found that vertical bias of SRTM and TanDEM-X, relative to the canopy height, is similar with negative values of up to −2.5 m and LE90s below 7.8 m in non-forest areas. In forests, the vertical bias of SRTM and TanDEM-X ranged from −0.5 to 4.1 m and LE90s from 7.2 to 11.0 m, respectively. The height differences between SRTM and TanDEM-X show moderate dependence on the slope and its orientation. LE90s for TDX-SRTM differences tended to be smaller for east-facing than for west-facing slopes, and varied, with aspect, by up to 1.5 m in non-forest areas and 3 m in forests, respectively. Finally, subtracting SRTM and NASA DEMs from TanDEM-X and Copernicus DEMs, respectively, successfully identified large areas of deforestation caused by hurricane Kyril in 2007 and a subsequent bark beetle disturbance in the Bohemian Forest. However, local errors in TanDEM-X, associated mainly with forest-covered west-facing slopes, resulted in erroneous identification of deforestation. Therefore, caution is needed when combining SRTM and TanDEM-X data in multitemporal studies in a mountain environment. Still, we can conclude that SRTM and TanDEM-X data represent suitable near global sources for the identification of deforestation in the period between the time points of their acquisition.

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Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data

BMC Genomics ◽

10.1186/s12864-021-07373-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Henriette Miko ◽

Yunjiang Qiu ◽

Bjoern Gaertner ◽

Maike Sander ◽

Uwe Ohler

Keyword(s):

Time Series ◽

Histone Modifications ◽

Gene Activation ◽

Expectation Maximization Algorithm ◽

Chromatin State ◽

Open Chromatin ◽

Multiple Time ◽

Enhancer Activity ◽

Chromatin States ◽

Multiple Time Points

Abstract Background Co-localized combinations of histone modifications (“chromatin states”) have been shown to correlate with promoter and enhancer activity. Changes in chromatin states over multiple time points (“chromatin state trajectories”) have previously been analyzed at promoter and enhancers separately. With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. Results We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. While the promoter side remains accessible across the time series, the enhancer side becomes dynamically more open towards the gene activation time point. Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. The code of the framework is available at https://github.com/henriettemiko/TimelessFlex. Conclusions TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time.

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