Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions

BACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. METHODS: Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. RESULTS: Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. CONCLUSIONS: Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions

Hans Urs Von Balthasar and Kenosis: The Pathway to Human Agency

The purpose of this dissertation is to examine the kenotic motif in the theology of Hans Urs von Balthasar, particularly in light of his concern to protect human agency. This dissertation argues that Balthasar views kenotic spiritual practice as the pathway to achieve true human agency. This kenotic pathway to agency is placed in contrast to Balthasar\u27s concept of original sin as an attempt by humanity to achieve agency on their own terms. The narrative of original sin results in two possible outcomes for Balthasar: a spiritual pathway toward the absorption of the self, which results in the annihilation of the self or, the autonomy of the self is emphasized to the degree that self-actualization becomes the goal of the spiritual journey and other humans are seen as obstacles to self-realization. This project explores the themes of kenosis within the doctrine of the Incarnation and Trinity as the solution to understanding human agency and as the answer to original sin in and through the Incarnation. The Christological and Trinitarian shape of sainthood and spirituality are explored in the final two chapters. Balthasar\u27s treatment of St. John of the Cross, St. Thérèse of Lisieux, and Elisabeth of the Trinity are examples of how the kenotic motif is revealed in the lives of the saints. The final chapter looks at Balthasar\u27s spirituality as thoroughly kenotic and that this kenotic activity cannot be systematized into a universal ethical or spiritual model; rather, it is enacted through discernment. This discernment is based on the norm of the gospel as hard sayings and as good news. Each individual human being is invited to take on a unique mission, which forms them into a theological person, those providing a deep and real sense of human agency. The dissertation ends with a speculative interaction of Balthasar\u27s kenotic thought with three other scholars, Edith Wyschogrod, Sarah Coakley, and Sallie McFague, in order to offer a glimpse into future discussions of kenosis in contemporary theology

Specification of Surface Roughness for Hydraulic Flow Test Plates

A study was performed to determine the surface roughness of the corrosion layer on aluminum clad booster fuel plates for the proposed Gas Test Loop (GTL) system to be incorporated into the Advanced Test Reactor (ATR) at the Idaho National Laboratory. A layer of boehmite (a crystalline, non-porous gamma-alumina hydrate) is typically pre-formed on the surface of the fuel cladding prior to exposure to reactor operation to prevent the uncontrolled buildup of corrosion product on the surface. A representative sample coupon autoclaved with the ATR driver fuel to produce the boehmite layer was analyzed using optical profilometry to determine the mean surface roughness, a parameter that can have significant impact on the coolant flow past the fuel plates. This information was used to specify the surface finish of mockup fuel plates for a hydraulic flow test model. The purpose of the flow test is to obtain loss coefficients describing the resistance of the coolant flow paths, which are necessary for accurate thermal hydraulic analyses of the water-cooled booster fuel assembly. It is recommended that the surface roughness of the boehmite layer on the fuel cladding be replicated for the flow test. While it is very important to know the order of magnitude of the surface roughness, this value does not need to be matched exactly. Maintaining a reasonable dimensional tolerance for the surface finish on each side of the 12 mockup fuel plates would ensure relative uniformity in the flow among the four coolant channels. Results obtained from thermal hydraulic analyses indicate that ±15% deviation from a surface finish (i.e., Ra) of 0.53 ìm would have a minimal effect on coolant temperature, coolant flow rate, and fuel temperature

Absence of Kaposi\u27s Sarcoma-Associated Herpesvirus DNA in Bacillary Angiomatosis-Peliosis Lesions

Bartonella henselae and B. quintana induce an unusual vascular proliferative tissue response known as bacillary angiomatosis (BA) and bacillary peliosis (BP) in some human hosts. The mechanisms of Bartonella-associated vascular proliferation remain unclear. Although host factors probably play a role, microbial coinfection has not been ruled out. Because of the vascular proliferative characteristics noted in both Kaposi\u27s sarcoma (KS) and BA and occasional colocalization of KS and BA, the possibility was explored that KS-associated herpes virus (KSHV) might be associated with BA lesions. Tissues with BA and positive and negative control tissues were tested for the presence of KSHV DNA by a sensitive polymerase chain reaction assay. Only 1 of 10 BA tissues, a splenic biopsy, was positive in this assay; this tissue was from a patient with concomitant KS of the skin. Thus, KSHV is probably not involved in the vascular proliferative response seen in BA-BP

Differences in White Matter Microstructure and Connectivity in Nontreatment‐Seeking Individuals with Alcohol Use Disorder

Background Diffusion‐weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol‐dependent populations. In addition, information on WM deficits in currently drinking, nontreatment‐seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD). Methods Thirty‐eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in‐house preprocessing of the DWI data, FA images were analyzed with tract‐based spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption. Results Smoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, family‐wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (ρ = −0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions. Conclusions NTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with self‐reported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcohol‐dependent individuals, after controlling for the key variable of cigarette smoking

Structural Integrity Program for INTEC Calcined Solids Storage Facilities

This report documents the activities of the structural integrity program at the Idaho Nuclear Technology and Engineering Center relevant to the high-level waste Calcined Solids Storage Facilities and associated equipment, as required by DOE M 435.1-1, “Radioactive Waste Management Manual.” Based on the evaluation documented in this report, the Calcined Solids Storage Facilities are not leaking and are structurally sound for continued service. Recommendations are provided for continued monitoring of the Calcined Solids Storage Facilities

Phylogenetic Signal Variation in the Genomes of Medicago (Fabaceae)

Genome-scale data offer the opportunity to clarify phylogenetic relationships that are difficult to resolve with few loci, but they can also identify genomic regions with evolutionary history distinct from that of the species history. We collected whole-genome sequence data from 29 taxa in the legume genus Medicago, then aligned these sequences to the Medicago truncatula reference genome to confidently identify 87 596 variable homologous sites. We used this data set to estimate phylogenetic relationships among Medicago species, to investigate the number of sites needed to provide robust phylogenetic estimates and to identify specific genomic regions supporting topologies in conflict with the genome-wide phylogeny. Our full genomic data set resolves relationships within the genus that were previously intractable. Subsampling the data reveals considerable variation in phylogenetic signal and power in smaller subsets of the data. Even when sampling 5000 sites, no random sample of the data supports a topology identical to that of the genome-wide phylogeny. Phylogenetic relationships estimated from 500-site sliding windows revealed genome regions supporting several alternative species relationships among recently diverged taxa, consistent with the expected effects of deep coalescence or introgression in the recent history of Medicago. [Medicago; phylogenomics; whole-genome resequencing.

Large-scale 3-dimensional quantitative imaging of tissues: state-of-the-art and translational implications

Recent developments in automated optical sectioning microscope systems have enabled researchers to conduct high resolution, three-dimensional (3D) microscopy at the scale of millimeters in various types of tissues. This powerful technology allows the exploration of tissues at an unprecedented level of detail, while preserving the spatial context. By doing so, such technology will also enable researchers to explore cellular and molecular signatures within tissue and correlate with disease course. This will allow an improved understanding of pathophysiology and facilitate a precision medicine approach to assess the response to treatment. The ability to perform large-scale imaging in 3D cannot be realized without the widespread availability of accessible quantitative analysis. In this review, we will outline recent advances in large-scale 3D imaging and discuss the available methodologies to perform meaningful analysis and potential applications in translational research

Inferences Drawn from a Risk Assessment Compared Directly with a Randomized Trial of a Home Drinking Water Intervention

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk = −365 cases/year, sham minus active; 95% confidence interval (CI), −2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches

Allele-specific demethylation at an imprinted mammalian promoter

A screen for imprinted genes on mouse Chromosome 7 recently identified Inpp5f_v2, a paternally expressed retrogene lying within an intron of Inpp5f. Here, we identify a novel paternally expressed variant of the Inpp5f gene (Inpp5f_v3) that shows a number of unusual features. Inpp5f_v3 initiates from a CpG-rich repeat region adjoining two B1 elements, despite previous reports that SINEs are generally excluded from imprinted promoters. Accordingly, we find that the Inpp5f_v3 promoter acquires methylation around the time of implantation, when many repeat families undergo de novo epigenetic silencing. Methylation is then lost specifically on the paternally derived allele during the latter stages of embryonic development, resulting in imprinted transcriptional activation on the demethylated allele. Methylation analyses in embryos lacking maternal methylation imprints suggest that the primary imprinting mark resides within an intronic CpG island ∼1 kb downstream of the Inpp5f_v3 transcriptional start site. These data support the hypothesis that SINEs can influence gene expression by attracting de novo methylation during development, a property likely to explain their exclusion from other imprinted promoters