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Abstract Plants adjust their allocation to different organs based on nutrient supply. In some plant species, symbioses with nitrogen‐fixing bacteria that live in root nodules provide an alternate pathway for nitrogen acquisition. Does access to nitrogen‐fixing bacteria modify plants' biomass allocation? We hypothesized that access to nitrogen‐fixing bacteria would have the same effect on allocation to aboveground versus belowground tissues as access to plentiful soil nitrogen. To test this hypothesis and related hypotheses about allocation to stems versus leaves and roots versus nodules, we conducted experiments with 15 species of nitrogen‐fixing plants in two separate greenhouses. In each, we grew seedlings with and without access to symbiotic bacteria across a wide gradient of soil nitrogen supply. As is common, uninoculated plants allocated relatively less biomass belowground when they had more soil nitrogen. As we hypothesized, nitrogen fixation had a similar effect as the highest level of fertilization on allocation aboveground versus belowground. Both nitrogen fixation and high fertilization led to ~10% less biomass allocated belowground (~10% more aboveground) than the uninoculated, lowest fertilization treatment. Fertilization reduced allocation to nodules relative to roots. The responses for allocation of aboveground tissues to leaves versus stems were not as consistent across greenhouses or species as the other allocation trends, though more nitrogen fixation consistently led to relatively more allocation to leaves when soil nitrogen supply was low. Synthesis: Our results suggest that symbiotic nitrogen fixation causes seedlings to allocate relatively less biomass belowground, with potential implications for competition and carbon storage in early forest development.

Background Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1‐point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown. Methods and Results Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010–2019) and followed up at a large, hybrid academic‐community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0–11). Adjusted Fine–Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2‐year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1‐point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06–1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12–1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08–1.19]). When considering AL as a time‐varying exposure, the peak associated MACE risk occurred with a 1‐point AL rise between 6 and 12 months post‐ breast cancer, lung cancer, and colorectal cancer diagnosis. Conclusions AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.

Abstract Background The Cancer Health Awareness through screeNinG and Education (CHANGE) initiative delivers cancer awareness education with an emphasis on modifiable risk factors and navigation to screening for prostate, breast, and colorectal cancers to residents of public housing communities who experience significant negative social determinants of health. Methods Residents of five communities participated. Community advisory board members were recruited and provided feedback to local environmental change projects, recruitment, and community engagement at each site. At each site, four education sessions were provided by trained facilitators on cancer risk factors and etiology, racial disparities, eligibility for cancer screening, and participation in clinical trials. Attendance, knowledge, attitudes and beliefs about cancer, and height, weight, and waist circumference were measured at baseline and 1‐week post‐CHANGE sessions. Results 90 residents (60% 65 and older years old, 33% male, 60% High School education, 93% AA) participated in the program. 95% completed post‐intervention evaluation. Participants were eligible for breast (n = 12), prostate (n = 15), and colorectal screening (n = 25) based on American Cancer Society guidelines, and 22 for tobacco cessation; 21 participants accepted navigation assistance for these services. At post‐test, participants significantly increased in knowledge and behaviors around obesity/overweight risk for cancer, nutrition, and physical activity. Colorectal, prostate, and breast cancer knowledge scores also increased, but were not significant. Conclusions CHANGE participants demonstrated improved health knowledge and intentions to improve their modifiable health behaviors. Participants reported being motivated and confident in seeking preventive care and satisfaction with community engagement efforts. Replication of this project in similar communities may improve knowledge and health equity among underserved populations.

Abstract Heterogeneous chemical cycles of pyrogenic nitrogen and halides influence tropospheric ozone and affect the stratosphere during extreme Pyrocumulonimbus (PyroCB) events. We report field‐derived N2O5 uptake coefficients, γ(N2O5), and ClNO2 yields, φ(ClNO2), from two aircraft campaigns observing fresh smoke in the lower and mid troposphere and processed/aged smoke in the upper troposphere and lower stratosphere (UTLS). Derived φ(ClNO2) varied across the full 0–1 range but was typically

Abstract Introduction The study's purpose was to examine 5‐year colorectal cancer (CRC) survival rates between White and Black patients. We also determined whether regional socioeconomic status (SES) is associated with CRC survival between White and Black patients in the Clayton, West Central, East Central, Southeast, and Northeast Georgia public health districts. Methods We performed a retrospective cohort analysis using data from the 1975 to 2016 Surveillance, Epidemiology, and End Results program. The 2015 United States Department of Agriculture Economic Research Services county typology codes were used to identify region‐level SES with persistent poverty, low employment, and low education. Kaplan–Meier method and Cox proportional hazard regression were performed. Results Among 10,876 CRC patients (31.1% Black patients), 5‐year CRC survival rates were lower among Black patients compared to White patients (65.4% vs. 69.9%; p

Abstract Background Maintaining a healthy lifestyle is an important factor in promoting positive outcomes for gynecologic cancer survivors. Methods We examined preventive behaviors among gynecologic cancer survivors (n = 1824) and persons without a history of cancer in a cross‐sectional analysis, using data from the 2020 Behavioral Risk Factor Surveillance System survey (BRFSS). BRFSS is a cross‐sectional telephone‐based survey of U.S. residents 18 years of age and older, which collects information about health‐related factors and use of preventive services. Results The prevalence rates of colorectal cancer screening were respectively 7.9 (95% CI: 4.0–11.9) and 15.0 (95% CI: 4.0–11.9) %‐points higher among gynecologic and other cancer survivors compared to that of 65.2% among those without any history of cancer. However, no differences were observed in breast cancer screening between gynecologic cancer survivors (78.5%) and respondents without any history of cancer (78.7%). Coverage of influenza vaccination among gynecologic cancer survivors were 4.0 (95% CI: 0.3–7.6) %‐points higher than that of the no cancer group, but 11.6 (95% CI: 7.6–15.6) %‐points lower than that of the other cancer group. Pneumonia vaccination rate among gynecologic cancer survivors, however, was not statistically different than that of other cancer survivors and respondents with no history of cancer. When examining modifiable risk behaviors, the prevalence of smoking among gynecologic cancer survivors was 12.8 (95% CI: 9.5–16.0) and 14.2 (95% CI: 10.8–17.7) %‐points higher than smoking prevalence among other cancer survivors and respondents without any history of cancer. The rate differentials were even higher in rural areas, 17.4 (95% CI: 7.2–27.6) and 18.4 (95% CI: 7.4–29.4) %‐points respectively. There were no differences in the prevalence of heavy drinking across the groups. Lastly, gynecologic and other cancer survivors were less likely to be physically active (Δ = −12.3, 95% CI: −15.8 to −8.8 and Δ = −6.9, 95% CI: −8.5 to −5.3, respectively) than those without any history of cancer. Conclusion Smoking prevalence among gynecologic cancer survivors is alarmingly high. Intervention studies are needed to identify effective ways to assist gynecologic cancer survivors to quit smoking and refrain from hazardous alcohol consumption. In addition, women with gynecologic malignancies should made aware of the importance of physical activity.

Abstract Purpose Investigating CRC screening rates and rurality at the county‐level may explain disparities in CRC survival in Georgia. Although a few studies examined the relationship of CRC screening rates, rurality, and/or CRC outcomes, they either used an ecological study design or focused on the larger population. Methods We conducted a retrospective analysis utilizing data from the 2004–2010 Surveillance, Epidemiology, and End Results Program. The 2013 United States Department of Agriculture rural–urban continuum codes and 2004–2010 National Cancer Institute small‐area estimates for screening behaviors were used to identify county‐level rurality and CRC screening rates. Kaplan–Meier method and Cox proportional hazard regression were performed. Results Among 22,160 CRC patients, 5‐year CRC survival rates were lower among CRC patients living in low screening areas in comparison with intermediate/high areas (69.1% vs. 71.6% /71.3%; p‐value = 0.030). Patients living in rural high‐screening areas also had lower survival rates compared to non‐rural areas (68.2% vs. 71.8%; p‐value = 0.009). Our multivariable analysis demonstrated that patients living in intermediate (HR, 0.91; 95% CI, 0.85–0.98) and high‐screening (HR, 0.92; 95% CI, 0.85–0.99) areas were at 8%–9% reduced risk of CRC death. Further, non‐rural CRC patients living in intermediate and high CRC screening areas were 9% (HR, 0.91; 95% CI, 0.83–0.99) and 10% (HR, 0.90; 95% CI, 0.82–0.99) less likely to die from CRC. Conclusions Lower 5‐year survival rates were observed in low screening and rural high‐screening areas. Living in intermediate/high CRC screening areas was negatively associated with the risk of CRC death. Particularly, non‐rural patients living in intermediate/high‐screening areas were 8%–9% less likely to die from CRC. Targeted CRC screening resources should be prioritized for low screening and rural communities.

Abstract The heterogeneous hydrolysis of dinitrogen pentoxide (N2O5) is an important pathway in nitrate formation; however, its formation rate and relative contribution to total particulate nitrate (pNO3‐) are highly variable. Here we report that nocturnal pNO3‐ formation via N2O5 hydrolysis is dependent on the regime defined by the ratio of NO2 to O3. Nocturnal pNO3‐ formation via N2O5 hydrolysis is suppressed in an O3‐limited regime but enhanced in a NO2‐limited regime. The results have crucial implications for effective control of nitrate pollution in the future. An exclusive decrease in NO2 will decrease nocturnal pNO3‐ formation in a NO2‐limited regime but may be less effective or even increase nocturnal pNO3‐ formation in an O3‐limited regime.

Abstract Background While patient‐reported outcome measures (PROMs) have benefit in cancer clinical trials, real‐world applications are lacking. This study describes the method of implementation of a cancer enterprise‐wide PROMs platform. Methods After establishing a multispecialty stakeholder group within a large integrated health system, domain‐specific instruments were selected from the National Institutes of Health's Patient‐Reported Outcomes Measurement Information System (PROMIS) instruments (pain interference, fatigue, physical function, and depression) and were administered at varying frequencies throughout each patient's cancer journey. All cancer patients with an oncologic visit were eligible to complete the PROMs prior to the visit using a patient portal, or at the time of the visit using a tablet. PROMs were integrated into clinical workflow. Clinical partnerships were essential for successful implementation. Descriptive preliminary data were compared using multivariable logistic regression to determine the factors associated with method of PROMs completion. Results From September 16, 2020 to July 23, 2021, 23 of 38 clinical units (60.5%) implemented PROMs over 2392 encounters and 1666 patients. Approximately one third of patients (n = 629, 37.8%) used the patient portal. Black patients (aOR 0.70; 95% CI: 0.51–0.97) and patients residing in zip codes with higher percentage of unemployment (aOR: 0.07, 95% CI: 0.01–0.41) were among the least likely to complete PROMs using the patient portal. Conclusions Successful system‐wide implementation of PROMs among cancer patients requires engagement from multispecialty stakeholders and investment from clinical partners. Attention to the method of PROMs collection is required in order to reduce the potential for disparities, such as Black populations and those residing in areas with high levels of unemployment.

Abstract Macrosystem‐scale research is supported by many ecological networks of people, infrastructure, and data. However, no network is sufficient to address all macrosystems ecology research questions, and there is much to be gained by conducting research and sharing resources across multiple networks. Unfortunately, conducting macrosystem research across networks is challenging due to the diversity of expertise and skills required, as well as issues related to data discoverability, veracity, and interoperability. The ecological and environmental science community could substantially benefit from networking existing networks to leverage past research investments and spur new collaborations. Here, we describe the need for a “network of networks” (NoN) approach to macrosystems ecological research and articulate both the challenges and potential benefits associated with such an effort. We describe the challenges brought by rapid increases in the volume, velocity, and variety of “big data” ecology and highlight how a NoN could build on the successes and creativity within component networks, while also recognizing and improving upon past failures. We argue that a NoN approach requires careful planning to ensure that it is accessible and inclusive, incorporates multimodal communications and ways to interact, supports the creation, testing, and promulgation of community standards, and ensures individuals and groups receive appropriate credit for their contributions. Additionally, a NoN must recognize important trade‐offs in network architecture, including how the degree of centralization of people, infrastructure, and data influence network scalability and creativity. If implemented carefully and thoughtfully, a NoN has the potential to substantially advance our understanding of ecological processes, characteristics, and trajectories across broad spatial and temporal scales in an efficient, inclusive, and equitable manner.

Abstract Background Many cancer survivors face financial difficulties that prevent them from receiving appropriate health care. Racial/ethnic disparities in receipt of health care have been reported among cancer survivors, but recent data for important racial/ethnic subgroups of the US population are lacking. Methods To learn more about barriers to healthcare access faced by cancer survivors, we analyzed data from the NIH “All of Us” Research Program. Data were analyzed about demographic factors and other personal characteristics, personal medical history of cancer, healthcare utilization, and access to care. Results As of November 2020, a total of 5426 participants had a history of cancer (excluding skin cancer). About 88.2% were non‐Hispanic White; 3.9% were Black, African American, or African; 1.3% were Asian; 4.1% were Hispanic, Latino, or Spanish; and 1.2% reported more than one race. Just over one‐half had an annual income of $75,000 or greater. The majority of the participants (71.7%) were college graduates or had an advanced degree. About 47.0%% had private health insurance, 41.0% had Medicare, 6.0% had Medicaid, and the remainder had military, Veterans Affairs, other insurance, or no health insurance. Frequently cited reasons for delayed care in the past 12 months were “had to pay out of pocket for some or all of the procedures,” “deductible was too high/or could not afford the deductible,” “couldn't afford the copay,” “couldn't get time off work,” and “were nervous about seeing a health care provider.” Discussion A minority of cancer survivors who participated in the NIH “All of Us” Program had difficulty paying for health care in the past 12 months. Of particular concern are minorities such as African American and Hispanic cancer survivors along with those who are low income.

Abstract Objectives Novel coronavirus (COVID‐19) is a global pandemic currently spreading rapidly across the United States. We provide a comprehensive look at COVID‐19 epidemiology across the state of Georgia, which includes vast rural communities that may be disproportionately impacted by the spread of this infectious disease. Methods All 159 Georgia counties were included in this study. We examined the geographic variation of COVID‐19 in Georgia from March 3 through April 24, 2020 by extracting data on incidence and mortality from various national and state datasets. We contrasted county‐level mortality rates per 100,000 population (MRs) by county‐level factors. Results Metropolitan Atlanta had the overall highest number of confirmed cases; however, the southwestern rural parts of Georgia, surrounding the city of Albany, had the highest bi‐weekly increases in incidence rate. Among counties with >10 cases, MRs were highest in the rural counties of Randolph (233.2), Terrell (182.5), Early (136.3), and Dougherty (114.2). Counties with the highest MRs (22.5–2332 per 100,000) had a higher proportion of: non‐Hispanic Blacks residents, adults aged 60+, adults earning

Abstract Cover cropping is a soil conservation practice widely investigated in agronomic crops, but less is known about cover crop implications in specialty cropping systems, particularly in a high disturbance system like potato (Solanum tuberosum L.). Brassica cover crops are popular in eastern Washington potato production, but brassica seed crop production in western Washington presents issues with use of brassica cover crops in the region's fresh‐market potato systems. To identify winter cover crops compatible with regional restrictions and climatic challenges in western Washington potato systems, trials including a no‐cover control, eight single species (including brassicas, grasses, and legumes), and a grass–legume mixture were conducted in Mount Vernon, WA, in 2018–2019 and 2019–2020. We examined cover crop and weed biomass production, potato yield and quality, and short‐term soil health impacts by measuring permanganate oxidizable carbon (POXC) and inorganic nitrogen before cover crop incorporation and at midseason. Cover crop biomass and weed suppression varied by year, with annual ryegrass (Lolium multiflorum Lam.) producing the most biomass in both years despite poorer weather conditions and reduced cover crop biomass in other treatments in 2020, making it a good cover crop candidate for western Washington. Both POXC and inorganic nitrogen were greater at midseason but did not vary among cover crop treatments, suggesting that temporal variation influences POXC and inorganic nitrogen more than a single winter of cover crops. Potato yield and tuber wireworm damage varied by year, but not across cover crop treatments, and tuber symptoms resembling black scurf did not vary by year nor treatment.

Abstract It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.

Abstract Durumwheat [Triticum turgidum L. ssp. durum (Desf.)] production is constrained by fungal diseases including stripe rust caused by Puccinia striiformis Westend. f. sp. tritici Erikss. (Pst). Continuous mining of germplasm for the discovery and deployment of stripe rust resistance (Yr) genes is needed to counter the impact of this disease. In this study, we evaluated a worldwide collection of 432 durum wheat accessions to seven U.S. Pst races that carry diverse virulence and avirulence combinations on wheat Yr genes. We found that 47–82% of the durum wheat accessions were susceptible to each of the tested Pst races. A total of 32 accessions were resistant to all seven races. Genome‐wide association studies (GWAS) using over 97,000 single‐nucleotide polymorphism markers generated from genotyping‐by‐sequencing of 364 accessions identified 56 quantitative trait loci (QTL) associated with all‐stage stripe rust resistance located on all 14 durum wheat chromosomes. Six of these QTL were associated with resistance to 2–4 Pst races, and none were associated with resistance to all seven races. The remaining 50 QTL were race specific. Eighteen of the 56 identified QTL had relatively large effects against at least one of the races. A map‐based comparison of the discovered QTL in this study with previously published Yr genes and QTL showed that 29 were previously identified, whereas the remaining 27 QTL appeared to be novel. This study reports effective sources of stripe rust resistance to contemporary races in the United States and shows that this durum wheat collection is abundant in novel resistance loci that can be transferred into adapted durum cultivars.

Abstract Spaceflight associated neuro‐ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. We exposed healthy subjects (n = 24) to strict 6° head‐down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and we monitored for ocular changes similar to findings that develop in SANS. Two‐thirds of the subjects received a daily 30‐min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short‐arm centrifugation to investigate whether this intervention would attenuate headward fluid shift‐induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9–51.9 µm, p

Abstract Fibrotic processes in the liver of non‐alcoholic steatohepatitis (NASH) patients cause microcirculatory dysfunction in the organ which increases blood vessel resistance and causes portal hypertension. Assessing blood vessel function in the liver is challenging, necessitating the development of novel methods in normal and fibrotic tissue that allow for drug screening and translation toward pre‐clinical settings. Cultures of precision cut liver slices (PCLS) from normal and fibrotic rat livers were used for blood vessel function analysis. Live recording of vessel diameter was used to assess the response to endothelin‐1, serotonin and soluble guanylate cyclase (sGC) activation. A cascade of contraction and relaxation events in response to serotonin, endothelin‐1, Ketanserin and sGC activity could be established using vessel diameter analysis of rat PCLS. Both the sGC activator BI 703704 and the sGC stimulator Riociguat prevented serotonin‐induced contraction in PCLS from naive rats. By contrast, PCLS cultures from the rat CCl4 NASH model were only responsive to the sGC activator, thus establishing that the sGC enzyme is rendered non‐responsive to nitric oxide under oxidative stress found in fibrotic livers. The role of the sGC pathway for vessel relaxation of fibrotic liver tissue was identified in our model. The obtained data shows that the inhibitory capacities on vessel contraction of sGC compounds can be translated to published preclinical data. Altogether, this novel ex vivo PCLS method allows for the differentiation of drug candidates and the translation of therapeutic approaches towards the clinical use.

Human induced pluripotent stem cells (hiPSCs) generated from patients and the derivative retinal cells enable the investigation of pathological and novel variants in relevant cell populations. Biallelic pathogenic variants in RPE65 cause early-onset severe retinal dystrophy (EOSRD) or Leber congenital amaurosis (LCA). Increasingly, regulatory-approved in vivo RPE65 retinal gene replacement therapy is available for patients with these clinical features, but only if they have biallelic pathological variants and sufficient viable retinal cells. In our cohort of patients, we identified siblings with early-onset severe retinal degeneration where genomic studies revealed compound heterozygous variants in RPE65, one a known pathogenic missense variant and the other a novel synonymous variant of uncertain significance. The synonymous variant was suspected to affect RNA splicing. Since RPE65 is very poorly expressed in all tissues except the retinal pigment epithelium (RPE), we generated hiPSC-derived RPE cells from the parental carrier of the synonymous variant. Sequencing of RNA obtained from hiPSC-RPE cells demonstrated heterozygous skipping of RPE65 exon 2 and the introduction of a premature stop codon in the mRNA. Minigene studies confirmed the splicing aberration. Results from this study led to reclassification of the synonymous variant to a pathogenic variant, providing the affected patients with access to RPE65 gene replacement therapy.

Purpose. To report a case of bilateral ampiginous choroiditis following presumed SARS-CoV-2 infection. Case Description. A 25-year-old woman presented with metamorphopsia and a paracentral scotoma in her left eye. She endorsed night sweats, headache, and new-onset anosmia beginning 1 week before her visual symptoms. She also had multiple confirmed ill COVID-19 contacts at her workplace before the onset of her symptoms. Funduscopic examination and multimodal imaging revealed placoid lesions in the macula and midperiphery of both eyes consistent with ampiginous choroiditis. COVID-19 antibody testing returned positive for IgG, and an extensive systemic evaluation was otherwise unremarkable. She was treated with oral prednisone and azathioprine with stabilization of the retinal lesions and no progression of her symptoms. Conclusions. Ampiginous choroiditis is an inflammatory chorioretinopathy with an unknown pathogenic mechanism that often necessitates early immunomodulatory therapy. This report suggests that SARS-CoV-2 infection may trigger chorioretinal inflammation in susceptible hosts.

Background. Diabetic retinopathy and kidney disease share underlying mechanisms of microvascular damage and are often comorbid in people with diabetes. We evaluated whether there is a relationship between retinal capillary perfusion as measured by swept-source optical coherence tomography angiography and estimated glomerular filtration rate (eGFR) and albuminuria in patients with diabetes and chronic kidney disease (CKD). Method. A cross-sectional pilot study was conducted at the University of Washington among a subset of participants with diabetes and CKD participating in a larger cohort study. Participants were excluded if they were known to have kidney disease from conditions other than diabetes. Ten participants (11 eyes) were included. Retinal nonperfusion (RNP) and vessel density (VD) were measured by swept-source optical coherence tomography angiography in 30° and 60° field of view (FOV) regions centered at the fovea. Correlations of RNP and VD with eGFR and albuminuria were analyzed. Results. Participants had a mean age of 72 years, hemoglobin A1c of 8.1%, eGFR of 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio of 162 mg/g. Mean (SD) RNP was 6.6% (4.2%) and 16.9% (7.7%) in 30° and 60° FOV regions, respectively. eGFR was negatively correlated to RNP in both the 30° and 60° FOV regions (R = −0.69, p=0.004, and R = −0.46, p=0.057, respectively), and correlations were stronger among a subset of 7 participants with evidence of diabetic retinopathy on exam and fundus photos. The estimated GFR was not significantly correlated with vessel density. Urine albumin-to-creatinine ratio was not significantly correlated with RNP or VD. Conclusions. Our proof-of-concept study showed that lower eGFR was significantly correlated with retinal nonperfusion in participants with diabetes and CKD. Advanced retinal imaging may enhance the noninvasive evaluation of kidney function in diabetes.

Abstract Pacific salmon acquire most of their biomass in the ocean before returning to spawn and die in coastal streams and lakes, thus providing subsidies of marine‐derived nitrogen (MDN) to freshwater and terrestrial ecosystems. Recent declines in salmon abundance have raised questions of whether managers should mitigate for losses of salmon MDN subsidies. To test the long‐term importance of salmon subsidies to riparian ecosystems, we measured soil nitrogen cycling in response to a 20‐yr manipulation where salmon carcasses were systematically removed from one bank and deposited on the opposite bank along a 2‐km stream in southwestern Alaska. Soil samples were taken at different distances from the stream bank along nine paired transects and measured for organic and inorganic nitrogen concentrations, and nitrogen transformation rates. Marine‐derived nitrogen was measured using 15N/14N for bulk soils, and NH4+ and NO3− soil pools. Stable isotope analyses confirmed 15N/14N was elevated on the salmon‐enhanced bank compared to the salmon‐depleted bank. However, 15N/14N values of plant‐available inorganic nitrogen exceeded the 15N/14N of salmon inputs, highlighting nitrogen isotope fractionation in soils that raises significant methodological issues with standard MDN assessments in riparian systems. Surprisingly, despite 20 yr of salmon supplementation, the presence of MDN did not cause a long‐term increase in soil nitrogen availability. This finding indicates the importance of MDN to ecosystem nitrogen biogeochemistry, and riparian vegetation may be overestimated for some systems. Given that essential nutrients can also be pollutants, we urge more critical analyses of the role of MDN to inform compensatory mitigation programs targeting salmon nutrient enhancement.

Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

BackgroundThe structural elements of the vascular wall, namely, extracellular matrix and smooth muscle cells (SMCs), contribute to the overall stiffness of the vessel. In this study, we examined the crosslinking‐dependent and crosslinking‐independent roles of tissue transglutaminase (TG2) in vascular function and stiffness. Methods and ResultsSMCs were isolated from the aortae of TG2−/− and wild‐type (WT) mice. Cell adhesion was examined by using electrical cell–substrate impedance sensing and PicoGreen assay. Cell motility was examined using a Boyden chamber assay. Cell proliferation was examined by electrical cell–substrate impedance sensing and EdU incorporation assays. Cell micromechanics were studied using magnetic torsion cytometry and spontaneous nanobead tracer motions. Aortic mechanics were examined by tensile testing. Vasoreactivity was studied by wire myography. SMCs from TG2−/− mice had delayed adhesion, reduced motility, and accelerated de‐adhesion and proliferation rates compared with those from WT. TG2−/− SMCs were stiffer and displayed fewer cytoskeletal remodeling events than WT. Collagen assembly was delayed in TG2−/− SMCs and recovered with adenoviral transduction of TG2. Aortic rings from TG2−/− mice were less stiff than those from WT; stiffness was partly recovered by incubation with guinea pig liver TG2 independent of crosslinking function. TG2−/− rings showed augmented response to phenylephrine‐mediated vasoconstriction when compared with WT. In human coronary arteries, vascular media and plaque, high abundance of fibronectin expression, and colocalization with TG2 were observed. ConclusionsTG2 modulates vascular function/tone by altering SMC contractility independent of its crosslinking function and contributes to vascular stiffness by regulating SMC proliferation and matrix remodeling.

Leaf rust (caused by Erikss. []) is increasingly impacting durum wheat ( L. var. ) production with the recent appearance of races with virulence to widely grown cultivars in many durum producing areas worldwide. A highly virulent race on durum wheat was recently detected in Kansas. This race may spread to the northern Great Plains, where most of the US durum wheat is produced. The objective of this study was to identify sources of resistance to several races from the United States and Mexico at seedling stage in the greenhouse and at adult stage in field experiments. Genome-wide association study (GWAS) was used to identify single-nucleotide polymorphism (SNP) markers associated with leaf rust response in a worldwide durum wheat collection of 496 accessions. Thirteen accessions were resistant across all experiments. Association mapping revealed 88 significant SNPs associated with leaf rust response. Of these, 33 SNPs were located on chromosomes 2A and 2B, and 55 SNPs were distributed across all other chromosomes except for 1B and 7B. Twenty markers were associated with leaf rust response at seedling stage, while 68 markers were associated with leaf rust response at adult plant stage. The current study identified a total of 14 previously uncharacterized loci associated with leaf rust response in durum wheat. The discovery of these loci through association mapping (AM) is a significant step in identifying useful sources of resistance that can be used to broaden the relatively narrow leaf rust resistance spectrum in durum wheat germplasm.

Perineuronal nets (PNNs) are extracellular molecules that form around neurons near the end of critical periods during development. They surround neuronal cell bodies and proximal dendrites. PNNs inhibit the formation of new connections and may concentrate around rapidly firing inhibitory interneurons. Previous work characterized the important role of perineuronal nets in plasticity in the visual system, amygdala, and spinal cord of rats. In this study, we use immunohistochemistry to survey the distribution of perineuronal nets in representative areas of the primate brain. We also document changes in PNN prevalence in these areas in animals of different ages. We found that PNNs are most prevalent in the cerebellar nuclei, surrounding >90% of the neurons there. They are much less prevalent in cerebral cortex, surrounding less than 10% of neurons in every area that we examined. The incidence of perineuronal nets around parvalbumin-positive neurons (putative fast-spiking interneurons) varies considerably between different areas in the brain. Our survey indicates that the presence of PNNs may not have a simple relationship with neural plasticity and may serve multiple functions in the central nervous system.

Parastagonospora (syn. , , ) (Berk.) Quaedvleig, Verkley & Crous is a necrotrophic fungal pathogen that causes the disease Septoria nodorum blotch (SNB) on wheat ( L. subsp. ). The fungus produces necrotrophic effectors (NEs) that cause cell death when recognized by corresponding host genes, which ultimately leads to disease. To date, eight host gene–NE interactions have been described in the wheat– system. Here, we report the identification and partial characterization of a ninth interaction involving a -produced NE designated SnTox7 and a wheat gene designated . SnTox7 is a small protein with an estimated size less than 30 kDa and largely resistant to heat and chemical treatment. The gene governs sensitivity to SnTox7 and was delineated to a 2.7-cM interval on the long arm of wheat chromosome 2D. The –SnTox7 interaction explained 33% of the variation in disease among a segregating population, indicating that the interaction plays a prominent role in the development of SNB. The sensitivity allele was identified in the hexaploid wheat cultivar Timstein, but evaluation of a set of 52 hexaploid lines of diverse origin indicated that few genotypes harbored a functional allele, thus indicating that is relatively rare. The identification of the –SnTox7 interaction adds to our knowledge of the wheat– pathosystem, which has become a model for necrotrophic specialist fungal pathogens and their interactions with plants leading to necrotrophic effector-triggered susceptibility.

A previously healthy 22-year-old African American woman presented with bilateral vision loss associated with headache. Her ocular examination was significant for bilateral retinal arterial “boxcarring,” retinal whitening, retinal hemorrhages, and cherry red spots. She was diagnosed with bilateral central retinal artery occlusions and was hospitalized due to concomitant diagnosis of stroke and hypercoagulable state. She was also found to be in heart failure and kidney failure. Rheumatology was consulted and she was diagnosed with catastrophic antiphospholipid syndrome in association with systemic lupus erythematosus. Approximately 7 months after presentation, the patient’s vision improved and remained stable at 20/200 and 20/80.

Posttraumatic iris implantation cysts are rare ocular findings that are often associated with poor visual outcomes. Iris implantation cysts can present clinicians with diagnostic and therapeutic challenges given their variable presentations and frequently destructive nature. In this paper, we provide descriptions of two unusual cases of posttraumatic iris implantation cysts. The first case is of a recurrent keratin-filled iris implantation cyst that developed after open globe injury and intraocular implantation of cilia and was treated with cyst debulking procedures, injections of 5-Fluorouracil, and iridocyclectomy. The second case is of recurrent posttraumatic serous iris implantation cysts that were treated with laser, cyst aspiration, and injections of 5-Fluorouracil. We use these cases as a platform to discuss the different manifestations of implantation cysts, the roles of anterior segment optical coherence tomography, ultrasound biomicroscopy, and histopathology in facilitating timely and accurate diagnosis and review the range of available therapeutic modalities. We discuss conservative treatment approaches, including the novel use of 5-Fluorouracil therapy as an adjunct therapy, as well as more aggressive surgical excision requiring ocular reconstruction. Through a discussion of these cases and review of the literature, we provide recommendations to assist clinicians in managing this uncommon but vision-threatening condition and minimizing complications.

Objective: The genital mycoplasmas, Ureaplasma urealyticum and Mycoplasma hominis, are commonly identified in the vagina of healthy pregnant women. However, these microorganisms are the most common isolates from the amniotic fluids of women in preterm labor. The mechanisms responsible for vaginal colonization and ascent to the uterus remain undetermined. We evaluated the association between U. urealyticum and M. hominis vaginal colonization and the presence of pro-inflammatory and anti-inflammatory interleukin-1 system components in asymptomatic pregnant women of different ethnicities.

Objective: To investigate whether clinical criteria could differentiate between women with vulvovaginitis who were culture positive or negative for vaginal Candida species.

Objectives: Recurrent vulvovaginitis remains difficult to diagnose accurately and to treat. The present investigation evaluated the utility of testing vaginal specimens from women with symptomatic recurrent vulvovaginitis for Candida species by polymerase chain reaction (PCR) and for cytokine responses.

Sympathetic denervation in a 20‐year‐old, gray, Thorough‐bred‐Percheron gelding was manifested by cutaneous hyperthermia and sweating over the right side of the body, demarcated by a line from the withers to the elbow and extending cranially. There was cutaneous hyperthermia over the right side of the head, but other signs of Horner's syndrome (sweating, ptosis, miosis, enophthalmos) were not present. The pattern of cutaneous hyperthermia and sweating was consistent with sympathetic denervation localized to the cervicothoracic ganglion, and thoracic radiographs revealed increased density in the craniodorsal thorax. Cytologic evaluation of a sample of pleural effusion revealed mesothelial cells containing melanin and cells suggestive of melanocytes or melanoblasts. Treatment with oral cimetidine and intrapleural cisplatin was not successful. A necropsy was not performed, but the clinical findings supported a diagnosis of thoracic melanoma involving the cervicothoracic ganglion.

Objective: This study aims to determine the pathophysiology of vulvar vestibulitis and to evaluate currently used treatment options.

The 60kD heat shock protein (hsp60) is a highly conserved protein and a dominant antigen of most pathogenic bacteria. In some women, chronic or repeated upper genital tract infections with Chlamydia trachomatis, and possibly with other microorganisms, induces immune sensitization to epitopes of hsp60 that are present in both the microbial and human hsp60. Once a woman becomes sensitized to these conserved epitpes, any subsequent induction of human or bacterial hsp60 expression will reactivate hsp60-sensitized lymphocytes and initiate a pro-inflammatory immune response. Hsp60 is expressed during the early stages of pregnancy, by both the embryo and the maternal decidua. We examined, therefore, whether women who were sensitized to hsp60 experienced less successful pregnancy outcomes compared to women who were not sensitized to this antigen. In women undergoing in vitro fertilization (IVF), the presence of cervical IgA antibodies reactive with the C. trachomatis hsp60 correlated with implantation failure after embryo transfer. Further analysis revealed that an immunodominant epitope for these IgA antibodies was an hsp60 epitope shared between C. trachomatis and man. In subsequent studies of women not undergoing IVF, cervical IgA antibodies to the human hsp60 were identified in 13 of 91 reproductive age women. This antibody was most prevalent in those women with a history of primary infertility (p = 0.003). In addition, cervical anti-hsp60 IgA correlated with the detection of the pro-inflammatory cytokines interferon-γ (p = 0.001) and tumor necrosis factor-α (p = 0.02) in the cervix. Conversely, women with proven fertility had the highest prevalence of the anti-inflammatory cytokine, interleukin 10, in their cervices (p = 0.001). In an analysis of serum samples in a third study, women with a history of two or more consecutive first trimester spontaneous abortions had a higher prevalence (p = 0.01) of IgG antibodies to the human hsp60 (36.8%) than did age matched fertile women (11.1%) or women with primary infertility (11.8%). Immune sensitization to epitopes expressed by the human hsp60 may reduce the probability of a successful pregnancy outcome due to reactivation of hsp60-reactive lymphocytes, induction of a pro-inflammatory cytokine response and interference with early embryo development and/or implantation.

Chlamydia trachomatis (CT) infections of the female genital tract, although frequently asymptomatic, are a major cause of fallopian-tube occlusion and infertility. Early stage pregnancy loss may also be due to an unsuspected and undetected CT infection. In vitro and in vivo studies have demonstrated that this organism can persist in the female genital tract in a form undetectable by culture. The mechanism of tubal damage as well as the rejection of an embryo may involve an initial immune sensitization to the CT 60 kD heat shock protein (HSP), followed by a reactivation of HSP-sensitized lymphocytes in response to the human HSP and the subsequent release of inflammatory cytokines. The periodic induction of human HSP expression by various microorganisms or by noninfectious mechanisms in the fallopian tubes of women sensitized to the CT HSP may eventually result in tubal scarring and occlusion. Similarly, an immune response to human HSP expression during the early stages of pregnancy may interfere with the immune regulatory mechanisms required for the maintenance of a semiallogeneic embryo.

To determine whether a previous pelvic infection has an effect on the outcome of a subsequent pregnancy, we identified women with a diagnosis of pelvic inflammatory disease (PID), amnionitis, and postpartum or postabortal endometritis-salpingitis by a retrospective chart review of all patients admitted to the Department of Obstetrics and Gynecology at The New York Hospital-Cornell Medical Center between 1975 and 1977 and between 1985 and 1988. Antimicrobial regimens effective against Chlamydia trachomatis were initiated in 1985. Controls were randomly selected patients presenting during the same time period for routine examinations who had normal Pap smears and no infections. Both groups were comparable for age, race, gravity, and parity. Differences were evaluated by chi square analysis, using the Yates correction factor. We identified 183 women with a history of the above infections who subsequently conceived, and 82 controls. There were no differences in outcome between the two index groups. Term vaginal deliveries occurred in 14.2% of the women with a prior pelvic infection and in 56% of the controls (P < 0.001). Among the 97 women who had had PID, 21 (21.6%) had a spontaneous abortion in the subsequent pregnancy, as opposed to 6 (7.3%) of the controls (P = 0.013). In addition, eight of the women with PID (but no controls) went into preterm labor (P = 0.021). An increased incidence of preterm labor (P = 0.001) was also observed in women with a history of amnionitis. A history of endometritis was not associated with an increased prevalence of abnormal outcome in subsequent pregnancies. PID and amnionitis may adversely affect the outcome of subsequent pregnancies.

Yersinia enterocolitica septicemia is described in a patient with transfusional iron overload and a myelodysplastic syndrome. The organism was biotype 1 serotype 0:5,27 and carried a virulence-encoding plasmid. It was calcium-dependent, autoagglutinating and virulent to orally challenged mice, but not resistant to the bacteriocidal activity of serum. The patient had depressed neutrophil chemotaxis and bactericidal activity. In this case, both host and microbial factors were present to select out this particular bacteremic disease. Patients with iron overload states should be recognized as compromised hosts and potentially susceptible to spontaneous sepsis due to Y enterocolitica.