On the Classification of Brane Tilings

We present a computationally efficient algorithm that can be used to generate all possible brane tilings. Brane tilings represent the largest class of superconformal theories with known AdS duals in 3+1 and also 2+1 dimensions and have proved useful for describing the physics of both D3 branes and also M2 branes probing Calabi-Yau singularities. This algorithm has been implemented and is used to generate all possible brane tilings with at most 6 superpotential terms, including consistent and inconsistent brane tilings. The collection of inconsistent tilings found in this work form the most comprehensive study of such objects to date.Comment: 33 pages, 12 figures, 15 table

Graft healing in anterior cruciate ligament reconstruction

Successful anterior cruciate ligament reconstruction with a tendon graft necessitates solid healing of the tendon graft in the bone tunnel. Improvement of graft healing to bone is crucial for facilitating an early and aggressive rehabilitation and ensuring rapid return to pre-injury levels activity. Tendon graft healing in a bone tunnel requires bone ingrowth into the tendon. Indirect Sharpey fiber formation and direct fibrocartilage fixation confer different anchorage strength and interface properties at the tendon-bone interface. For enhancing tendon graft-to-bone healing, we introduce a strategy that includes the use of periosteum, hydrogel supplemented with periosteal progenitor cells and bone morphogenetic protein-2, and a periosteal progenitor cell sheet. Future studies include the use of cytokines, gene therapy, stem cells, platelet-rich plasma, and mechanical stress for tendon-to-bone healing. These strategies are currently under investigation, and will be applied in the clinical setting in the near future

Recommendation of RILEM TC 243-SGM: Functional requirements for surface repair mortars for historic buildings

Surface repair mortars are used for the compensation, or repair, of lost portions of surface materials in historic masonry buildings. It is recommended that their design and application should be performed in a wider context of conservation values related decision making, to prioritise preservation of original fabric, authenticity of approach and maintenance of integrity, and not just on technical principles alone. However, a technical context for their design does exist, that requires understanding of the properties of the substrate that they will be applied onto, and adherence to minimum aesthetic (colour and texture) requirements. The principles of physical, mechanical and chemical compatibility of repair apply and the attributes of the repair mortar should be carefully matched to the substrate alongside a sacrificial behaviour (not more durable than the material being replaced). Guidance is given on the design, application and the functional requirements that must be met when using surface repair mortars.Accepted Author ManuscriptHeritage & Technolog

Longitudinal evaluation of whole blood miRNA expression in firefighters

Background: Dysregulated microRNA (miRNA) expression could provide a mechanism linking firefighter exposure to increased cancer risk. Objective: To determine if changes in longitudinal miRNA expression in firefighters are associated with occupational exposures. Methods: Whole blood MiRNA was evaluated in 52 new recruits prior to live-fire training and 20–37 months later. Linear mixed effects models adjusted for age, ethnicity, BMI, and batch effects were used to determine associations separately for all fires and structure fires only between employment duration, cumulative fire-hours and fire-runs, and time since most recent fire with (1) nine a priori and (2) the full array of 799 miRNAs. Results: For multivariable models including all fires, two a priori miRNAs were associated with employment duration and four with time since most recent fire. For multivariable models restricted to structure fires, three a priori miRNAs were associated with employment duration and one with fire-runs. Additional miRNAs from the full array were associated with employment duration for all fires and/or structure fires. In general, tumor suppressive miRNAs decreased and oncogenic miRNAs increased with exposure. Significance: Changes in miRNAs may serve as biomarkers of exposure effects and a mechanism for increased cancer risk in firefighters. © 2021, The Author(s).Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach

Abstract Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers

517 The firefighter multicenter cancer cohort study: framework development and testing

Introduction Recent epidemiologic studies in the United States have demonstrated excess mortality rates for cancer in firefighters compared with the general population. Firefighters are exposed to multiple carcinogens in the workplace through skin contamination and inhalation. However, we currently do not understand which individual exposures are responsible for cancer in firefighters, the mechanisms by which these exposures cause cancer, or effective means of reducing exposures. Development of a large multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Methods The study is harmonising existing firefighter cohort studies in Arizona and Florida, and expanding to include the Boston Fire Department and volunteer and combination fire departments. The study framework components include an Oversight and Planning Board (OPB), a Data Coordination Centre (DCC), an Exposure Assessment Centre (EAC) and a Biomarker Analysis Centre (BAC). Results The OPB is providing oversight of the study through collaboration with fire service organisations and government agencies. The DCC is developing standardised participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. The EAC is developing a carcinogen exposure matrix using self-reported and quantitative exposure measurements to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. The BAC is carrying out pilot studies of epigenetic markers of carcinogenic effect and cancer risk comparing firefighters with a range of cumulative exposures and non-firefighter controls. Conclusion A framework is being established for the subsequent development of a large multicenter cohort study of cancer in the fire service; advance our understanding of firefighter exposures to carcinogens; and help identify biomarkers of carcinogen effect and cancer risk

Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk

Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per- and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q-value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically

Occupational Years of Service and Leukocyte Epigenetic Aging

ObjectiveThe aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length.MethodsThe study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States.ResultsIncumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality.ConclusionsLong-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers

Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q  < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases