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"Watson, David William"
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Monitoring moisture movement within modified concretes
The current work presents the results of a study into moisture movement within the surface region of concrete containing supplementary cementiceous additions (modified concrete). Samples were subjected to cycles of drying and wetting to study the influence of binder type, curing regime, and water/binder ratio on drying mass loss, cumulative volume gain during infiltration, internal relative humidity and electrical conductivity profiles within the surface 100mm. Binder types included plain OPC and OPC partially replaced with PFA, GGBS, Microsilica, and Metakaolin at water/binder ratios of w/b=0.4 and w/b=0.6.A brief review of non-destructive, in-situ durability test methods developed for use with concrete is presented, and relevant moisture transport theory regarding drying and infiltration is discussed. The background to electrical testing is discussed and developed.A number of conclusions are drawn regarding the influence of test parameters on the sorptive properties of concrete, and results illustrate the useful insight discretised electrical measurements can provide into the distribution and movement of moisture within the cover region. Electrical profiles are used to monitor the depth of influence of infiltration cycles and zone of influence of drying action. Regarding the latter, data are found to compare favourably with relative humidity measurements. The electrode response during infiltration is examined and the influence of the wetting-front shape is discussed. The relationship between resistivity and degree of saturation was studied for both concrete and mortar. Results are presented which allow in-situ estimates of degree of saturation profiles during a 24 hour infiltration test.The testing methodology was then extended to study a surface treatment (silane). Monitoring electrical conductivity through the surface region allowed measurement of the depth of penetration of silane treatment, and showed that although infiltration is reduced, drying moisture profiles were not measurably influenced by silane application.
Dissertation
American Labor and the Cold War
The American labor movement seemed poised on the threshold of unparalleled success at the beginning of the post-World War II era. Fourteen million strong in 1946, unions represented thirty five percent of non-agricultural workers. Why then did the gains made between the 1930s and the end of the war produce so few results by the 1960s?
This collection addresses the history of labor in the postwar years by exploring the impact of the global contest between the United States and the Soviet Union on American workers and labor unions. The essays focus on the actual behavior of Americans in their diverse workplaces and communities during the Cold War. Where previous scholarship on labor and the Cold War has overemphasized the importance of the Communist Party, the automobile industry, and Hollywood, this book focuses on politically moderate, conservative workers and union leaders, the medium-sized cities that housed the majority of the population, and the Roman Catholic Church. These are all original essays that draw upon extensive archival research and some upon oral history sources.
eBook
Inference of cell type content from human brain transcriptomic datasets illuminates the effects of age, manner of death, dissection, and psychiatric diagnosis
Psychiatric illness is unlikely to arise from pathology occurring uniformly across all cell types in affected brain regions. Despite this, transcriptomic analyses of the human brain have typically been conducted using macro-dissected tissue due to the difficulty of performing single-cell type analyses with donated post-mortem brains. To address this issue statistically, we compiled a database of several thousand transcripts that were specifically-enriched in one of 10 primary cortical cell types in previous publications. Using this database, we predicted the relative cell type content for 833 human cortical samples using microarray or RNA-Seq data from the Pritzker Consortium (GSE92538) or publicly-available databases (GSE53987, GSE21935, GSE21138, CommonMind Consortium). These predictions were generated by averaging normalized expression levels across transcripts specific to each cell type using our R-package BrainInABlender (validated and publicly-released on github). Using this method, we found that the principal components of variation in the datasets strongly correlated with the predicted neuronal/glial content of the samples. This variability was not simply due to dissection-the relative balance of brain cell types appeared to be influenced by a variety of demographic, pre- and post-mortem variables. Prolonged hypoxia around the time of death predicted increased astrocytic and endothelial gene expression, illustrating vascular upregulation. Aging was associated with decreased neuronal gene expression. Red blood cell gene expression was reduced in individuals who died following systemic blood loss. Subjects with Major Depressive Disorder had decreased astrocytic gene expression, mirroring previous morphometric observations. Subjects with Schizophrenia had reduced red blood cell gene expression, resembling the hypofrontality detected in fMRI experiments. Finally, in datasets containing samples with especially variable cell content, we found that controlling for predicted sample cell content while evaluating differential expression improved the detection of previously-identified psychiatric effects. We conclude that accounting for cell type can greatly improve the interpretability of transcriptomic data.
Journal Article
Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Participants: A Multicenter Prospective Study
Abstract
Context
Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking.
Objective
To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor.
Design
Multicenter, prospective study.
Setting
Twelve centers within the T1D Exchange Clinic Network.
Patients or Participants
Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index.
Intervention
Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days.
Main Outcome Measures
CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability.
Results
A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d).
Conclusion
By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies.
This study provides normative sensor glucose data in a healthy, nondiabetic population of children and adults.
Journal Article
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder
A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses (“controls”) and 34 patients with MDD. Our dataset covered ∼12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1) , and BHLHE41(DEC2) . The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.
Journal Article
Comprehensive evidence implies a higher social cost of CO2
The social cost of carbon dioxide (SC-CO
2
) measures the monetized value of the damages to society caused by an incremental metric tonne of CO
2
emissions and is a key metric informing climate policy. Used by governments and other decision-makers in benefit–cost analysis for over a decade, SC-CO
2
estimates draw on climate science, economics, demography and other disciplines. However, a 2017 report by the US National Academies of Sciences, Engineering, and Medicine
1
(NASEM) highlighted that current SC-CO
2
estimates no longer reflect the latest research. The report provided a series of recommendations for improving the scientific basis, transparency and uncertainty characterization of SC-CO
2
estimates. Here we show that improved probabilistic socioeconomic projections, climate models, damage functions, and discounting methods that collectively reflect theoretically consistent valuation of risk, substantially increase estimates of the SC-CO
2
. Our preferred mean SC-CO
2
estimate is $185 per tonne of CO
2
($44–$413 per tCO
2
: 5%–95% range, 2020 US dollars) at a near-term risk-free discount rate of 2%, a value 3.6 times higher than the US government’s current value of $51 per tCO
2
. Our estimates incorporate updated scientific understanding throughout all components of SC-CO
2
estimation in the new open-source Greenhouse Gas Impact Value Estimator (GIVE) model, in a manner fully responsive to the near-term NASEM recommendations. Our higher SC-CO
2
values, compared with estimates currently used in policy evaluation, substantially increase the estimated benefits of greenhouse gas mitigation and thereby increase the expected net benefits of more stringent climate policies.
Coupling advances in socioeconomic projections, climate models, damage functions and discounting methods yields an estimate of the social cost of carbon of US$185 per tonne of CO
2
—triple the widely used value published by the US government.
Journal Article
Craniotomy: True Sham for Traumatic Brain Injury, or a Sham of a Sham?
Neurological dysfunction after traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use “sham” (craniotomy alone) animals as controls. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. To test this hypothesis, 38 adult female rats were assigned to one of three groups: control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. The rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses compared to trephine or naïve rats. Finally, of the seven tested cytokines, KC-GRO and IFN-γ showed significant increases in both craniotomy models compared to naïve rats. We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating “sham” procedures should distinguish among sham, experimentally injured, and healthy/naïve animals, to help reduce confounding factors.
Journal Article