delta C-13 signatures of organic aerosols:Measurement method evaluation and application in a source study

Analysis of the stable carbon isotope 13C in organic carbon (OC) can give insight into sources and atmospheric processing of carbonaceous aerosols, provided the 13C source signatures are known. However, only few data on 13C signatures of OC emitted by common sources of carbonaceous aerosol are available in Europe. We present and evaluate an improved version of a measurement method to obtain δ13C signatures on organic aerosols desorbed from filter samples at three different desorption temperatures (200 °C, 350 °C and 650 °C) and apply it in a source study. With our calibration approach, the reproducibility of a L-Valine reference material desorbed at a single temperature step of 650 °C shows a standard deviation of 0.19‰ over a period of more than one year. The average δ13C value for this reference material over 248 measurements is −24.10‰, which shows only a slight bias to the nominal value of −24.03‰. Repeated analysis of ambient filter samples desorbed at three temperature steps show typical standard deviations of about 0.3‰ for all temperature steps (200 °C, 350 °C and 650 °C). Isotopic fractionation due to partial thermal desorption during the individual temperature steps was tested on single compound reference materials. It showed significant isotopic fractionation only at temperature steps, in which a very minor fraction of the compound was desorbed. Possible isotope effects caused by charring of organic material were investigated and found to be not significant. The thermal desorption method was applied to various source filter samples from the region of Naples, Italy. We analyzed two different biomass burning sources, exhaust from a city bus and traffic emissions collected in a tunnel and compared these to ambient filter samples from the same region. δ13C signatures of the total OC show values in a narrow range of about −28‰ to −26‰ for all sources, which does not allow a source apportionment only based on 13C. Nevertheless, the results add information to a source inventory of δ13C, where information of 13C in organic aerosol from specific emission sources are rare. City bus emissions show little variation of δ13C over the temperature steps, whereas biomass burning aerosol is enriched in 13C for OC desorbed at 650 °C. For PM10 samples in the urban tunnel an enrichment in δ13C at the 650 °C temperature steps was observed, which is likely caused by the contribution of carbonate carbon to the carbonaceous material desorbed at this temperature step

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis

Aims/hypothesis Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. Methods Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. Results In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (beta +/- SE 0.014 +/- 0.004 [mmol/l], p = 1.5 x 10(-3)) and higher fasting insulin (0.030 +/- 0.005 [log(e) pmol/l], p = 2.0 x 10(-10)). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the beta-Klotho (KLB) locus on fasting insulin (0.030 +/- 0.011 log(e) pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. Conclusions/interpretation In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis.Peer reviewe

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.Peer reviewe

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Food Insecurity in the United States of America: A Comparison 2 between the Great Recession and the COVID-19 Pandemic

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19, altered everyday life in the United States of America and around the world. In 2020, 20,727,942 people residing in the United States of America were infected, with 356,666 succumbing to the virus.” Social distancing measures discouraged in-person interaction which led to many businesses, schools, and food services having to operate at reduced capacity or to close completely. Soon after, revenues declined, employees were dismissed, and numerous businesses were forced to file bankruptcy. Consequently, the number of people in the United States of America who struggle to put food on the table has increased. Newspaper and media outlets showed long lines of people seeking assistance from food banks across the USA . This chapter discusses the economic ramification of spread mitigations strategies, a severe economic crisis, and a rapid increase in food insecurity

VARIATION IN GROWTH RATES OF EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) IN AN INVASIVE-DOMINATED HABITAT IN NORTH GEORGIA**

Habitat destruction, fragmentation, and degradation often leads to an increase in invasive, non-native plant species which can compete with native species for limiting resources, often reducing native biodiversity. Chinese privet (Ligustrom sinense) was introduced to the United States from China as an ornamental in the 19th century and is now a common invasive plant from Florida to Virginia and as far west as Texas and Oklahoma. Uncontrolled, Chinese privet (privet) can form dense understory stands that frequently shade out native plants and tree seedlings. The resulting monoculture may alter many ecological factors including hydrology, soil composition, vegetative food resources, and invertebrate community composition. Eastern box turtles (Terrapene carolina carolina), native to the eastern United States, are in decline throughout much of their range. Evidence shows that habitat loss and degradation are major contributing factors in the diminishing populations of Eastern Box Turtles (EBT). Habitat alterations have occurred in areas where Chinese privet and EBT ranges overlap; however, little data has been published regarding the impacts of privet on EBT ecology and physiology. Using morphological measurements collected on 37 EBT (19M, 18 F) radiotracked in northeastern Georgia between 2013-2022, we examined growth differences by sex and age class of individuals using habitats with varying amounts of privet coverage. Understanding how invasive habitats affect box turtle growth may be used to guide future conservation efforts and management decisions

AQUATIC HABITAT RESOURCE USE OF EASTERN BOX TURTLES IN NORTHEASTERN GEORGIA**

Abstract: Anthropogenic habitat loss, fragmentation, and degradation lead to decreases in resources, biodiversity, and ecosystem services; thus, understanding how species use specific resources is vital to conservation and restoration efforts. Eastern Box Turtles (Terrapene carolina carolina) are a primarily terrestrial species native to the eastern United States that has experienced population declines throughout its native range largely due to habitat loss and alterations. Although the species is considered primarily terrestrial, phylogenetic studies indicate Eastern Box Turtles (EBT) evolved from an aquatic turtle species, suggesting that aquatic habitats may represent an important resource for the species when considering conservation efforts. To investigate this use in northeastern Georgia, we analyzed habitat use of 50 individual EBT (29 M, 21 F) located using radiotelemetry 1-2 times per month for periods of 9-110 months between 2013-2022. Aquatic habitats at our study site included freshwater forested/shrub wetlands created by beaver activity along a permanent creek in addition to multiple, unconnected seepage wetland areas dominated by either Chinese Privet (Ligustrum sinense) or native woody and herbaceous vegetation. About a quarter of all radiolocations were recorded in wetland or seepage habitats; however individual use of these aquatic resources varied, with about 20% of the turtles having no locations recorded in a wetland or seepage area. The high percentage of EBT using aquatic habitats supports the need for consideration of aquatic habitat in conservation efforts