Assessing dissolved organic carbon export from Kopuatai bog, New Zealand

Peatlands sequester carbon (C) through CO₂ uptake and, ultimately, storage as peat. Carbon is lost from peatlands though gaseous pathways (as CO₂ and CH₄) and water pathways as dissolved organic C (DOC), dissolved inorganic C (DIC), particulate organic C (POC) or dissolved CO₂ and CH₄. Many studies have shown that the loss of C through DOC export is an important component of the annual C budget, but there are very few published studies where atmospheric fluxes of CO₂ and CH₄ and waterborne fluxes of DOC are measured at the same time. Also, little is known about the spatial variations in DOC concentration within peatlands and the processes leading to the delivery of DOC into rivers. The research described in this thesis focuses on understanding the ways in which vegetation, temperature, peat quality and hydrology interact to determine variability in DOC concentrations and export, both seasonally and spatially, at Kopuatai bog. DOC concentrations were measured at 14 sites across the bog for a year. At each site peat pore water was sampled from three different depths and represented three different vegetation types dominated by Empodisma robustum (jointed wire rush), Leptospermum scoparium (manuka) and Sporadanthus ferrugineus. There were no strong seasonal trends in DOC concentration, possibly due to the small seasonal range in temperatures. DOC concentrations varied spatially, with highest concentrations found under L. scoparium vegetation, likely due to differing chemical properties of plant materials leading to higher decomposition rates. DOC concentration did not vary significantly with depth. DOC export was estimated using a water balance based approach where evaporation (E), precipitation (P) and change in storage were measured to determine water discharge (Q) from the eddy covariance (EC) footprint. Discharge was then multiplied by average DOC concentrations within the EC footprint to derive DOC export. This method had not been directly applied in the literature. It was estimated that 11.7 ± 0.82 g C m⁻² of DOC was exported from the EC footprint from the year 1 February 2012 to 1 February 2013, which is at the lower end of the range when compared to literature values. DOC export had strong seasonal variation with highest export during the winter due to high rainfall and lowest in summer due to low rainfall. A simple method to estimate DOC export was proposed using the strong correlations between DOC export and monthly P and P–E. When annual DOC export was compared to annual net ecosystem exchange (NEE) at Kopuatai, DOC export was equivalent to only 6% of CO₂ sequestered in a year. This is in contrast to the literature where, on average, DOC export is often equal to around 25% of NEE. Preliminary analyses shows that NEE values are significantly higher at Kopuatai than NEE published for Northern Hemisphere peatlands and this is likely an effect of the dominance by vascular plants and the year-round growing conditions at Kopuatai

White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

Background Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55–59, 60–64, 65–69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2’ deoxycytidine [5-mdC] to 2’-deoxyguanine [dG], assuming [dG] = [5-mdC] + [2’-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6–1.3), 0.88 (95% CI, 0.6–1.3), and 0.84 (95% CI, 0.6–1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend = .39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Rural-Urban Differences in Hospital and Patient-Reported Outcomes Following Total Hip Arthroplasty

BACKGROUND: Rural patients have unique health-care factors influencing outcomes of arthroplasty, hypothetically putting these patients at increased risk for complications following total joint arthroplasty. The aim of this study is to better understand differences in patient outcomes and satisfaction between rural and urban patients receiving care in an urban setting and to provide more equitable care. METHODS: A retrospective chart review was performed on patients undergoing primary total hip arthroplasty at a single large academic center between January 2013 and August 2020. Demographic, operative, and hospital outcomes were obtained from the institutional electronic medical record. Rurality was determined by rural-urban code (RUC) classifications by zip code with RUC codes 1-3 defined as urban and RUC 4-10 defined as rural. RESULTS: Patients from urban areas were more likely to visit the emergency department within 30 days postoperatively ( = .006) and be readmitted within 90 days ( \u3c .001). However, unplanned ( \u3c .001) admissions were higher in the rural group. There was no statistical difference in postoperative complications ( = .4). At 6 months, rural patients had higher patient-reported outcome measures (PROMs) including Hip Disability and Osteoarthritis Outcome Score total ( = .05), Hip Disability and Osteoarthritis Outcome Score interval ( = .05), self-reported functional improvement ( \u3c .05), improvements in pain ( \u3c .05), and that the surgery met expectations ( \u3c .05). However, these values did not reach minimal clinically important difference. CONCLUSIONS: There may be differences in emergency department visits, readmissions, and PROMs in rural vs urban populations undergoing total hip arthroplasty in an urban setting. Patient access to care and attitudes of rural patients toward health care may underlie these findings. Understanding differences in PROMs, satisfaction, and hospital-based outcomes based on rurality is essential to provide equitable arthroplasty care

Detection of promoter methylation of tumor suppressor genes in serum DNA of breast cancer cases and benign breast disease controls

Tumors are capable of shedding DNA into the blood stream. This shed DNA may be recovered from serum or plasma. The objective of this study was to evaluate whether pyrosequencing promoter DNA in a panel of 12 breast cancer-related genes (APC, BRCA1, CCND2, CDH1, ESR1, GSTP1, HIN1, P16, RARβ, RASSF1, SFRP1 and TWIST) to measure the degree of methylation would lead to a useful serum-based marker of breast cancer. Serum was obtained from women who were about to undergo a breast biopsy or mastectomy at three hospitals from 1977 to 1987 in Grand Rapids, Michigan. We compared the methylation status of 12 genes in serum DNA obtained from three groups of postmenopausal women (mean age at blood collection: 63.0 y; SD 9.9; range 35–91): breast cancer cases with lymph node-positive disease (n = 241); breast cancer cases with lymph node-negative disease (n = 63); and benign breast disease control subjects (n = 234). Overall, median levels of promoter methylation were low, typically below 5%, for all genes in all study groups. For all genes, median levels of methylation were higher (by 3.3 to 47.6%) in lymph node-positive breast cancer cases than in the controls. Comparing mean methylation level between lymph-node positive cases and controls, the most statistically significant findings, after adjustment of the false-positive rate (q-value), were for TWIST (p = 0.04), SFRP1 (p = 0.16), ESR1 (p = 0.17), P16 (p = 0.19) and APC (p = 0.19). For two of these four genes (TWIST, P16), the median methylation level was also highest in lymph-node positive cases, intermediate in lymph node-negative cases and lowest in the controls. The percent of study subjects with mean methylation scores ≥ 5% was higher among lymph node-positive cases than controls for ten genes, and significantly higher for HIN1 and TWIST (22.0 vs. 12.2%, p = 0.04 and 37.9 vs. 24.5%, p = 0.004, respectively). Despite relatively consistent variation in methylation patterns among groups, these modest differences did not provide sufficient ability to distinguish between cases and controls in a clinical setting

From What We Wear to What We Eat: Upgrading in Global Value Chains

In recent academic debates, upgrading has emerged as a key way for developing countries to meet the competitive challenges of globalisation and trade liberalisation. This article draws on global commodity chains literature to comparatively explore the conditions within which upgrading occurs in two sectors: export horticulture in Kenya and textile/apparel in Tamil Nadu, India. In both sectors upgrading into new products, functions or markets has generated increased employment and sustained incomes. However, firms in horticulture and textile/apparel are governed by a small number of global buyers with demanding requirements. Firms without the linkages to these buyers or the capabilities to meet their requirements can be locked out of international markets. The article concludes that insertion into global value chains creates varying outcomes for developing country firms, both providing and circumscribing opportunities for broad‐based development

Rural-Urban Differences in Hospital and Patient-Reported Outcomes Following Total Hip Arthroplasty

Background: Rural patients have unique health-care factors influencing outcomes of arthroplasty, hypothetically putting these patients at increased risk for complications following total joint arthroplasty. The aim of this study is to better understand differences in patient outcomes and satisfaction between rural and urban patients receiving care in an urban setting and to provide more equitable care. Methods: A retrospective chart review was performed on patients undergoing primary total hip arthroplasty at a single large academic center between January 2013 and August 2020. Demographic, operative, and hospital outcomes were obtained from the institutional electronic medical record. Rurality was determined by rural-urban code (RUC) classifications by zip code with RUC codes 1-3 defined as urban and RUC 4-10 defined as rural. Results: Patients from urban areas were more likely to visit the emergency department within 30 days postoperatively (P = .006) and be readmitted within 90 days (P < .001). However, unplanned (P < .001) admissions were higher in the rural group. There was no statistical difference in postoperative complications (P = .4). At 6 months, rural patients had higher patient-reported outcome measures (PROMs) including Hip Disability and Osteoarthritis Outcome Score total (P = .05), Hip Disability and Osteoarthritis Outcome Score interval (P = .05), self-reported functional improvement (P < .05), improvements in pain (P < .05), and that the surgery met expectations (P < .05). However, these values did not reach minimal clinically important difference. Conclusions: There may be differences in emergency department visits, readmissions, and PROMs in rural vs urban populations undergoing total hip arthroplasty in an urban setting. Patient access to care and attitudes of rural patients toward health care may underlie these findings. Understanding differences in PROMs, satisfaction, and hospital-based outcomes based on rurality is essential to provide equitable arthroplasty care

White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

Background Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55–59, 60–64, 65–69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2’ deoxycytidine [5-mdC] to 2’-deoxyguanine [dG], assuming [dG] = [5-mdC] + [2’-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6–1.3), 0.88 (95% CI, 0.6–1.3), and 0.84 (95% CI, 0.6–1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend = .39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.This article is published as Sturgeon, Susan R., J. Richard Pilsner, Kathleen F. Arcaro, Kaoru Ikuma, Haotian Wu, Soon-Mi Kim, Nayha Chopra-Tandon et al. "White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)." Breast Cancer Research 19, no. 1 (2017): 1-11. doi: https://doi.org/10.1186/s13058-017-0886-6. © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/