Measurement of Complement Activation via Plasma-Soluble C5b-9 Comparison with Terminal Complement Complex Staining in a Series of Kidney Biopsies.

INTRODUCTION: With the emergence of therapeutic complement inhibitors, there is a need to identify patients with complement-driven inflammation. C5b-9 is the terminal product of the three complement pathways and therefore a marker of total complement activation. We present a pilot study which aims to assess whether plasma soluble C5b-9 (sC5b-9) correlates with terminal complement complex (TCC) staining in kidney tissue. The secondary aim was to assess the utility of plasma sC5b-9 as part of routine workup in kidney patients undergoing kidney biopsy. METHODS: Thirty-seven patients undergoing kidney biopsy had plasma sC5b-9 and TCC staining on kidney tissue performed. Additional blood markers including creatinine, haemoglobin, CRP, factor H, factor I, and midkine levels were also taken. These parameters were correlated with the histological diagnoses. Patients were divided into a diseased group (n = 31) and a control group (n = 6) consisting of transplanted kidneys with minor or no changes. Of the biopsies in the control group, 50% were performed as per protocol, and the other 50% were performed due to clinical need. RESULTS: There was no correlation found between plasma sC5b-9 and TCC kidney staining. Elevated sC5b-9 levels were found in a heterogeneous group of patients but were associated with higher CRP and lower haemoglobin levels. Overall, there was more TCC kidney staining in the diseased group compared with the control group, and a trend was observed of diabetic, primary membranous nephropathy, and amyloidosis patients having more intense glomerular and peritubular/interstitial staining. CONCLUSION: Plasma sC5b-9 as a marker of total complement activation does not correlate with TCC kidney staining. This discordance suggests that plasma sC5b-9 and TCC staining are distinct markers of disease. TCC staining reflects chronicity and tissue deposition of complement over time. Conversely, plasma sC5b-9 concentrations change rapidly and reflect systemic complement activation. Complement activation was present in a heterogeneous group of kidney disease, indicating the underlying role of complement in many disorders.

Impact of integrated care coordination on pediatric asthma hospital presentations.

Introduction: Frequent asthma attacks in children result in unscheduled hospital presentations. Patient centered care coordination can reduce asthma hospital presentations. In 2016, The Sydney Children's Hospitals Network launched the Asthma Follow up Integrated Care Initiative with the aim to reduce pediatric asthma emergency department (ED) presentations by 50% through developing and testing an integrated model of care led by care coordinators (CCs). Methods: The integrated model of care was developed by a multidisciplinary team at Sydney Children's Hospital Randwick (SCH,R) and implemented in two phases: Phase I and Phase II. Children aged 2-16 years who presented ≥4 times to the ED of the SCH,R in the preceding 12 months were enrolled in Phase I and those who had ≥4 ED presentations and ≥1 hospital admissions with asthma attack were enrolled in Phase II. Phase I included a suite of interventions delivered by CCs including encouraging parents/carers to schedule follow-up visits with GP post-discharge, ensuring parents/carers are provided with standard asthma resource pack, offering referrals to asthma education sessions, sending a letter to the child's GP advising of the child's recent hospital presentation and coordinating asthma education webinar for GPs. In addition, in Phase II CCs sent text messages to parents/carers reminding them to follow-up with the child's GP. We compared the change in ED visits and hospital admissions at baseline (6 months pre-enrolment) and at 6-and 12-months post-enrolment in the program. Results: During December 2016-January 2021, 160 children (99 in Phase I and 61 in Phase II) were enrolled. Compared to baseline at 6- and 12-months post-enrolment, the proportion of children requiring ≥1 asthma ED presentations reduced by 43 and 61% in Phase I and 41 and 66% in Phase II. Similarly, the proportion of children requiring ≥1 asthma hospital admissions at 6- and 12-months post-enrolment reduced by 40 and 47% in Phase I and 62 and 69% in Phase II. Conclusion: Our results support that care coordinator led integrated model of asthma care which enables integration of acute and primary care services and provides families with asthma resources and education can reduce asthma hospital presentations in children.

Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors.

FoundationOne®CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology to examine 324 cancer genes in solid tumors. F1CDx reports known and likely pathogenic short variants (SVs), copy number alterations (CNAs), and select rearrangements, as well as complex biomarkers including tumor mutational burden (TMB) and microsatellite instability (MSI), in addition to genomic loss of heterozygosity (gLOH) in ovarian cancer. CGP services can reduce the complexity of biomarker testing, enabling precision medicine to improve treatment decision-making and outcomes for cancer patients, but only if test results are reliable, accurate, and validated clinically and analytically to the highest standard available. The analyses presented herein demonstrate the extensive analytical and clinical validation supporting the F1CDx initial and subsequent FDA approvals to ensure high sensitivity, specificity, and reliability of the data reported. The analytical validation included several in-depth evaluations of F1CDx assay performance including limit of detection (LoD), limit of blank (LoB), precision, and orthogonal concordance for SVs (including base substitutions [SUBs] and insertions/deletions [INDELs]), CNAs (including amplifications and homozygous deletions), genomic rearrangements, and select complex biomarkers. The assay validation of >30,000 test results comprises a considerable and increasing body of evidence that supports the clinical utility of F1CDx to match patients with solid tumors to targeted therapies or immunotherapies based on their tumor's genomic alterations and biomarkers. F1CDx meets the clinical needs of providers and patients to receive guideline-based biomarker testing, helping them keep pace with a rapidly evolving field of medicine.

Driver Mutation Variant Allele Frequency in Circulating Tumor DNA and Association with Clinical Outcome in Patients with Non-Small Cell Lung Cancer and EGFR- and KRAS-Mutated Tumors.

Clinical implementation of mutational analysis for next-generation sequencing-based assays has largely been of a binary nature, with pathogenic mutations being reported as either positive or negative. Actionability on the continuous output of variant allele frequency (VAF) has not been well characterized in the clinical setting, thus limiting its use. In this study, analytical validity and performance of the short variant VAF based on a next-generation sequencing-based liquid biopsy assay, FoundationOne Liquid CDx, were evaluated through assessment of precision, analytical accuracy, limit of blank, and limit of detection. Analytical validation of VAF values measured by using FoundationOne Liquid CDx supports that these values are accurate, precise, robust, and linear with the true VAF value. The association of allele frequency of clinically relevant short variants in circulating-free DNA and the association with overall survival for patients using real-world data were also assessed. The results of the association analysis indicate that VAF of the predictive biomarker mutation negatively correlates with overall survival of patients with non-small cell lung cancer.

Development and validation of a risk score to identify children at risk of life-threatening asthma.

OBJECTIVE: To develop and validate a prediction risk score for identification of children at risk of developing life-threatening asthma (LTA). METHODS: Our study utilized existing medical records and retrospective analysis to develop and validate a risk score. The study population included children aged 2-17 years, admitted with a primary diagnosis of asthma, to Sydney Children's Hospital between 2011-2016. Children admitted in the intensive care unit with asthma at risk of LTA (cases) and those admitted into general ward (comparison group), were randomly divided into a derivation and a validation cohort. Candidate predictors from derivation cohort were selected through multivariable regression, which were used to estimate each child's risk of developing LTA in the validation cohort. Predictive performance of the risk score was evaluated by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test. RESULTS: The study population comprised of 1171 children; 586 in the derivation and 585 in the validation cohort. Four independent candidate variables from derivation cohort (age at admission, socioeconomic status, a family history of asthma/atopy and previous asthma hospitalizations) were retained in the predictive model (AUROC 0.759; 95% CI, 0.694-0.823), with a sensitivity of 78.5% and specificity of 46.6%. CONCLUSIONS: Our risk algorithm based on routinely collected clinical data may be used to develop a user-friendly risk score for early identification and monitoring of children at risk of developing LTA.

Nest survival of Seaside Sparrows (Ammospiza maritima) in the wake of the Deepwater Horizon oil spill.

In 2010, the Deepwater Horizon oil spill released an estimated 4.9 million barrels of oil into the Gulf of Mexico, damaging coastal ecosystems. Seaside Sparrows (Ammospiza maritima)-a year-round resident of Gulf Coast salt marshes-were exposed to oil, as shown by published isotopic and molecular analyses, but fitness consequences have not been clarified. We monitored nests around two bays in Plaquemines Parish, Louisiana, USA from 2012-2017 to assess possible impacts on the nesting biology of Seaside Sparrows. A majority of nests failed (76% of known-fate nests, N = 252 nests, 3521 exposure-days) during our study, and predation was the main cause of nest failure (~91% of failed nests). Logistic exposure analysis revealed that daily nest survival rate: (1) was greater at nests with denser vegetation at nest height, (2) was higher in the more sheltered bay we studied, (3) decreased over the course of the breeding season in each year, and (4) was not correlated with either sediment polycyclic aromatic hydrocarbon concentrations or estimated predator abundance during the years for which we had those data. Although the Deepwater Horizon spill impacted other aspects of Seaside Sparrow ecology, we found no definitive effect of initial oiling or oiled sediment on nest survival during 2012-2017. Because predation was the overwhelming cause of nest failure in our study, additional work on these communities is needed to fully understand demographic and ecological impacts of storms, oil spills, other pollutants, and sea-level rise on Seaside Sparrows and their predators.

Assessment of Variation in Care Following Hospital Discharge for Children with Acute Asthma.

PURPOSE: To evaluate potential variation in care management pathways following hospital discharge for children with asthma in New South Wales, Australia. METHODS: A cross-sectional web-based survey was conducted in emergency departments (EDs) and paediatric units of public hospitals with more than five paediatric beds within New South Wales, Australia, between July 2018 and March 2019. Nursing and medical staff in EDs and paediatric units who had cared for children aged under 18 years with asthma in the preceding 12 months were invited to participate in this study. Outcome measures included use of clinical practice guidelines and asthma action plan (AAP); advice on post-hospitalization follow-up; provision of asthma education for parents/carers; availability of community-based asthma services; communication with schools/childcare services. RESULTS: A total of 502 participants (236 nursing and 266 medical staff, response rate=22%) from 37 hospitals were included. Overall, the use of AAP was not universal (median=90%; IQR=81-96%) with significant difference across local health districts (LHDs) (88.6%, 95% CI=85.4-91.3) and between EDs and paediatric wards (p=9.4×10-9); and a range of asthma clinical practice guidelines were used. Post-hospitalization follow-up within 2-3 days was recommended by 70% of the respondents, but only 8% reported that hospitals had a system in place to ensure follow-up compliance. Formal asthma education sessions (27% respondents) were seldom provided to parents/carers during hospital stays, especially in EDs (14% respondents). Less than 50% of the respondents were aware of any asthma community services for children and only 4% reported that schools/childcare services were notified about the child's hospital admission for an asthma flare up. CONCLUSION: There are marked variations in the post-hospitalization asthma care and community management for children in NSW. An integrated standardized model of care may improve health outcomes in children with asthma.

A Randomized Trial to Improve Adherence to Follow-up Eye Examinations Among People With Glaucoma.

INTRODUCTION: Appointment nonadherence is common among people with glaucoma, making it difficult for eye care providers to monitor glaucoma progression. Our objective was to determine whether the use of patient navigators, in conjunction with social worker support, could increase adherence to recommended follow-up eye appointments. METHODS: A randomized, controlled trial evaluated the effectiveness of an intervention that used patient navigators and social workers to improve patient adherence to follow-up eye care compared with usual care. Participants with glaucoma and other eye diseases (N = 344) were identified at primary care clinics in community settings through telemedicine screening of imaging and then randomized to enhanced intervention (EI) or usual care (UC). Data on participants' visits with local ophthalmologists were collected for up to 3 years from randomization. Groups were compared for timely attendance at the first visit with the local ophthalmologist and adherence to recommended follow-up visits. RESULTS: Timely attendance at the first visit was higher for EI than UC (74.4% vs 39.0%; average relative risk [aRR] = 1.85; 95% CI, 1.51-2.28; P < .001). Rates of adherence to recommended annual follow-up during year 1 were 18.6% in the EI group and 8.1% in the usual care group (aRR = 2.08; 95% CI, 1.14-3.76; P = .02). The aRR across years 2 and 3 was 3.92 (95% CI, 1.24-12.43; P = .02). CONCLUSION: An intervention using patient navigators and social workers doubled the rate of adherence to annual recommended follow-up eye care compared with usual care in community settings, and was effective at increasing connections with local ophthalmologists. Interventions to further improve long-term adherence are needed.

Community-based interventions for childhood asthma using comprehensive approaches: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to determine the effectiveness of comprehensive community-based interventions with ≥ 2 components in improving asthma outcomes in children. METHODS: A systematic search of Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), Cochrane Library and hand search of reference collections were conducted to identify any research articles published in English between 2000 and 2019. All studies reporting community-based asthma interventions with ≥ 2 components (e.g., asthma self-management education, home environmental assessment or care coordination etc.) for children aged ≤ 18 years were included. Meta-analyses were performed using random-effects model to estimate pooled odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Of the 2352 studies identified, 21 studies were included in the final analysis: 19 pre-post interventions, one randomised controlled trial (RCT) and one retrospective study. Comprehensive asthma programs with multicomponent interventions were associated with significant reduction in asthma-related Emergency Department (ED) visits (OR = 0.26; 95% CI 0.20-0.35), hospitalizations (OR = 0.24; 95% CI 0.15-0.38), number of days (mean difference = - 2.58; 95% CI - 3.00 to - 2.17) and nights with asthma symptoms (mean difference = - 2.14; 95% CI - 2.94 to - 1.34), use of short-acting asthma medications/bronchodilators (BD) (OR = 0.28; 95% CI 0.16-0.51), and increase use of asthma action plan (AAP) (OR = 8.87; 95% CI 3.85-20.45). CONCLUSION: Community-based asthma care using more comprehensive approaches may improve childhood asthma management and reduce asthma related health care utilization.

Long-term persistence of wildlife populations in a pastoral area.

Facilitating coexistence between people and wildlife is a major conservation challenge in East Africa. Some conservation models aim to balance the needs of people and wildlife, but the effectiveness of these models is rarely assessed. Using a case-study approach, we assessed the ecological performance of a pastoral area in northern Tanzania (Manyara Ranch) and established a long-term wildlife population monitoring program (carried out intermittently from 2003 to 2008 and regularly from 2011 to 2019) embedded in a distance sampling framework. By comparing density estimates of the road transect-based long-term monitoring to estimates derived from systematically distributed transects, we found that the bias associated with nonrandom placement of transects was nonsignificant. Overall, cattle and sheep and goat reached the greatest densities and several wildlife species occurred at densities similar (zebra, wildebeest, waterbuck, Kirk's dik-dik) or possibly even greater (giraffe, eland, lesser kudu, Grant's gazelle, Thomson's gazelle) than in adjacent national parks in the same ecosystem. Generalized linear mixed models suggested that most wildlife species (8 out of 14) reached greatest densities during the dry season, that wildlife population densities either remained constant or increased over the 17-year period, and that herbivorous livestock species remained constant, while domestic dog population decreased over time. Cross-species correlations did not provide evidence for interference competition between grazing or mixed livestock species and wildlife species but indicate possible negative relationships between domestic dog and warthog populations. Overall, wildlife and livestock populations in Manyara Ranch appear to coexist over the 17-year span. Most likely, this is facilitated by existing connectivity to adjacent protected areas, effective anti-poaching efforts, spatio-temporal grazing restrictions, favorable environmental conditions of the ranch, and spatial heterogeneity of surface water and habitats. This long-term case study illustrates the potential of rangelands to simultaneously support wildlife conservation and human livelihood goals if livestock grazing is restricted in space, time, and numbers.

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin.

As availability of precision therapies expands, a well-validated circulating cell-free DNA (cfDNA)-based comprehensive genomic profiling assay has the potential to provide considerable value as a complement to tissue-based testing to ensure potentially life-extending therapies are administered to patients most likely to benefit. Additional data supporting the clinical validity of cfDNA-based testing is necessary to inform optimal use of these assays in the clinic. The FoundationOne®Liquid CDx assay is a pan-cancer cfDNA-based comprehensive genomic profiling assay that was recently approved by FDA. Validation studies included >7,500 tests and >30,000 unique variants across >300 genes and >30 cancer types. Clinical validity results across multiple tumor types are presented. Additionally, results demonstrated a 95% limit of detection of 0.40% variant allele fraction for select substitutions and insertions/deletions, 0.37% variant allele fraction for select rearrangements, 21.7% tumor fraction for copy number amplifications, and 30.4% TF for copy number losses. The limit of detection for microsatellite instability and blood tumor mutational burden were also determined. The false positive variant rate was 0.013% (approximately 1 in 8,000). Reproducibility of variant calling was 99.59%. In comparison with an orthogonal method, an overall positive percent agreement of 96.3% and negative percent agreement of >99.9% was observed. These study results demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations in addition to complex biomarkers such as microsatellite instability, blood tumor mutational burden, and tumor fraction. Critically, clinical validity data is presented across multiple cancer types.

Role of technology in improving knowledge and confidence in asthma management in school staff.

Objective: To investigate the effectiveness of technology enabled learning in improving asthma first aid knowledge and self-confidence in providing asthma first aid to children in staff within a school setting. Study Design: A prospective randomized parallel study using a pre and post test design was conducted across Metropolitan schools of New South Wales (NSW), Australia. School staff in selected schools were randomly assigned to receive first aid asthma management training via a self-directed multimedia eBook learning resource or standard face-to-face training. Staff completed a 14 item validated Asthma First Aid Knowledge Questionnaire and a 4 item, 10-point Likert-scale asthma management self-confidence questionnaire immediately pre and post training. Results: 148 school staff from 46 schools were recruited with a total of 59 (78%) staff completing the eBook training and 62 (86%) completing face-to-face training. The mean asthma first aid knowledge score and self-confidence score in managing asthma increased significantly (p < 0.0001) in the eBook training group post training. There was no significant difference in the increase in the mean scores post training between the eBook and face-to-face training groups (p = 0.11). Conclusion: Asthma management knowledge and self-confidence increased in school staff following the eBook training. In school settings where human resources for health education are limited, technology enabled learning may be substituted to provide a self-directed approach to asthma first aid management training.

Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Intraocular Pressure Measurements Found in a Population at High Risk for Glaucoma.

PRECIS: Intraocular pressure (IOP) measurements, when used during telemedicine eye screening alongside nonmydriatic fundus photography, were shown to improve the likelihood of accurate glaucoma and glaucoma-related diagnoses at the follow-up eye examination. PURPOSE: To determine if IOP measurements, used as an adjunct to nonmydriatic fundus photography, are useful in glaucoma telemedicine screening. MATERIALS AND METHODS: A total of 902 high-risk individuals were screened for glaucoma at 7 primary care practices and 4 Federally Qualified Health Centers using telemedicine. Screening at visit 1 included fundus photography, assessing family history of glaucoma, and IOP measurements using a hand-held rebound tonometer. Participants with suspicious nerve findings for glaucoma, IOP>21 mm Hg or other ocular pathologies were invited for a follow-up appointment with an ophthalmologist (visit 2). RESULTS: Of the 902 individuals screened at visit 1, 19.6% (n=177/902) had elevated IOP (>21 mm Hg). Fifteen participants were found to have an IOP>30 mm Hg at visit 1, including 2 with an IOP of >40 mm Hg. Among all who attended visit 2 (n=347), 10.9% had glaucoma and 7.2% had ocular hypertension. For participants having both suspicious nerve findings and IOP>21 mm Hg compared with those with neither, the odds ratio (OR) of being diagnosed with glaucoma was 4.48 (95% CI, 1.50-13.93; P=0.007), whereas for participants with suspicious discs and IOP≤21 mm Hg the OR was 2.04 (95% CI, 0.83-5.53; P=0.15). CONCLUSIONS: In this telemedicine vision screening setting, having a higher IOP at the screening visit increased the likelihood of receiving a final diagnosis of glaucoma. Therefore, this study supports incorporating IOP measurements, using a portable tonometer, into vision screening programs in high-risk populations.

Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: confirmation between eye screening and comprehensive eye examination diagnoses.

AIMS: To evaluate agreement between ocular findings of a telemedicine eye screening (visit 1) with diagnoses of a comprehensive eye examination (visit 2). METHODS: A primary care practice (PCP)-based telemedicine screening programme incorporating fundus photography, intraocular pressure (IOP) and clinical information was conducted. Eligible individuals were African American, Hispanic/Latino or Asian over the age of 40; Caucasian individuals over age 65; and adults of any ethnicity over age 40 with a family history of glaucoma or diabetes. Participants with abnormal images or elevated IOP were invited back for a complete eye examination. Both visit 1 and visit 2 were conducted at participants' local PCP. Ocular findings at visit 1 and eye examination diagnoses at visit 2 are presented, including a cost analysis. RESULTS: Of 906 participants who attended visit 1, 536 were invited to visit 2 due to ocular findings or unreadable images. Among the 347 (64.9%) who attended visit 2, 280 (80.7%) were diagnosed with at least one ocular condition. Participants were predominately women (59.9%) and African American (65.6%), with a mean age (±SD) of 60.6±11.0 years. A high diagnostic confirmation rate (86.0%) was found between visit 1 and visit 2 for any ocular finding. Of 183 with suspicious nerves at visit 1, 143 (78.1%) were diagnosed as glaucoma or glaucoma suspects at visit 2. CONCLUSIONS: This screening model may be adapted and scaled nationally and internationally. Referral to an ophthalmologist is warranted if abnormal or unreadable fundus images are detected or IOP is >21 mm Hg. TRIAL REGISTRATION NUMBER: NCT02390245.

Experimental manipulation of a signal trait reveals complex phenotype-behaviour coordination.

Animals use morphological signals such as ornamental traits or weaponry to mediate social interactions, and the extent of signal trait elaboration is often positively associated with reproductive success. By demonstrating relationships between signal traits and fitness, researchers often make inferences about how behaviour operates to shape those outcomes. However, detailed information about fine-scale individual behaviour, and its physiological basis, can be difficult to obtain. Here we show that experimental manipulations to exaggerate a signal trait (plumage colour) and concomitant changes in testosterone and stress-induced corticosterone levels altered social interactivity between manipulated males and their social mates. On average, darkened males did not have higher levels of interactivity than unmanipulated males; however, males who experienced a greater shift in colour (pale to dark), a larger, positive change in testosterone levels, and a dampened stress-induced corticosterone response had a larger increase in the number of interactions with their social mate post-manipulation compared to pre-manipulation. This work provides new insights into the integration and real-time flexibility of multivariate phenotypes and direct evidence for the role of social interactions in pair bond maintenance.

Polycyclic aromatic hydrocarbon exposure in seaside sparrows (Ammodramus maritimus) following the 2010 Deepwater Horizon oil spill.

The seaside sparrow (Ammodramus maritimus) is an abundant and permanent resident of coastal salt marshes impacted by the 2010 BP Deepwater Horizon oil spill. Such terrestrial species are often overlooked in the aftermath of marine spills, despite the potential for long-term oil exposure. We sampled the livers of seaside sparrows residing in oiled and unoiled sites from 2011 to 2014 and quantified expression of cytochrome p450 1A (CYP1A), a gene involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). In August 2011, CYP1A expression was markedly higher in birds from an oiled site compared to an unoiled site, but differences had disappeared by June 2012. In June 2013, CYP1A expression was elevated compared to 2012 levels on all sites, including those collected from sites that had not been directly oiled during the spill. This rise in CYP1A expression was possibly due to Hurricane Isaac, which made landfall near our sites between the 2012 and 2013 sampling periods. CYP1A expression was significantly attenuated again in June 2014. We also collected sediment samples from the same marshes for a total concentration analysis of PAHs. The PAH concentrations in sediment samples exhibited a similar pattern to the CYP1A data, supporting the link between marsh PAHs and bird CYP1A expression. These results indicate that contamination from marine oil spills can immediately extend to terrestrial ecosystems, and that storms, weather, or other factors may influence subsequent spatial and temporal oil exposure for several additional years.

Longitudinal Changes in Serum Glucose Levels are Associated with Metabolic Changes in Alzheimer's Disease Related Brain Regions.

BACKGROUND: The association between longitudinal changes in serum glucose level and longitudinal changes in [18F] Fluorodeoxyglucose-PET (FDG PET) measurements of Alzheimer's disease (AD) risk are unknown. OBJECTIVE: To investigate whether variation in serum glucose levels across time are associated with changes in FDG PET measurements of cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer's disease (AD). METHODS: Participants are a subset of a prospective cohort study investigating FDG PET, apolipoprotein E (APOE) ɛ4, and risk for AD which includes data from baseline, interim, and follow up visits over 4.4±1.0-years. An automated brain-mapping algorithm was utilized to characterize and compare associations between longitudinal changes in serum glucose levels and longitudinal changes in rCMRgl. RESULTS: This study included 80 adults aged 61.5±5 years, including 38 carriers and 42 non-carriers of the APOE ɛ4 allele. Longitudinal increases in serum glucose levels were associated with longitudinal CMRgl decline in the vicinity of parietotemporal, precuneus/posterior cingulate, and prefrontal brain regions preferentially affected by AD (p < 0.05, corrected for multiple comparisons). Findings remained significant when controlled for APOE ɛ4 status and baseline and advancing age. CONCLUSIONS: Additional studies are needed to clarify and confirm the relationship between longitudinal changes in peripheral glucose and FDG PET measurements of AD risk. Future findings will set the stage on the use of FDG PET in the evaluation of possible interventions that target risk factors for the development of AD.

Prevalence and Risk of Severe Cognitive Impairment in Advanced Chronic Kidney Disease.

Background: Our primary goal is to describe the prevalence, severity, and risk of cognitive impairment (CI) by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) in a cohort enriched for advanced chronic kidney disease (CKD; eGFR < 45), adjusting for albuminuria, as measured by urine albumin-to-creatinine ratio (UACR, in mg/g). As both eGFR and albuminuria are associated with CI risk in CKD, we also seek to determine the extent that eGFR remains a useful biomarker for risk of CI in those with CKD and concomitant albuminuria. Methods: Chi-square tests measured the prevalence of severe CI and mild cognitive impairment (MCI) by eGFR level. Logistic regression models and generalized linear models measured risk of CI by eGFR, adjusted for UACR. Results: Participants were 574 adults with a mean age of 69; 433 with CKD (eGFR < 60, nondialysis) and 141 controls (eGFR ≥ 60). Forty-eight percent of participants with CKD had severe CI or MCI. The prevalence of severe CI was highest (25%) in those with eGFR < 30. eGFR < 30 was only associated with severe CI in those without albuminuria (UACR < 30; OR = 3.3; p = .02) and was not associated with MCI in similar models. Conclusions: One quarter of those with eGFR < 30 had severe CI. eGFR < 30 was associated with over threefold increased odds of severe CI in those with UACR < 30, but not with UACR > 30, suggesting that eGFR < 30 is a valid biomarker for increased risk of severe CI in those without concomitant albuminuria.

Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Methods and Screening Results.

PURPOSE: To describe methodology and screening results from the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study. DESIGN: Screening program results for a prospective randomized clinical trial. METHODS: Individuals were recruited who were African-American, Hispanic/Latino, or Asian over age 40 years; white individuals over age 65 years; and any ethnicity over age 40 years with a family history of glaucoma or diabetes. Primary care offices and Federally Qualified Health Centers were used for telemedicine (Visit 1). Two posterior fundus photographs and 1 anterior segment photograph were captured per eye in each participant, using a nonmydriatic, autofocus, hand-held fundus camera (Volk Optical, Mentor, Ohio, USA). Medical and ocular history, family history of glaucoma, visual acuity, and intraocular pressure measurements using the ICare rebound tonometer (ICare, Helsinki, Finland) were obtained. Images were read remotely by a trained retina reader and a glaucoma specialist. RESULTS: From April 1, 2015, to February 6, 2017, 906 individuals consented and attended Visit 1. Of these, 553 participants were female (61.0%) and 550 were African-American (60.7%), with a mean age of 58.7 years. A total of 532 (58.7%) participants had diabetes, and 616 (68%) had a history of hypertension. During Visit 1, 356 (39.3%) participants were graded with a normal image. Using image data from the worse eye, 333 (36.8%) were abnormal and 155 (17.1%) were unreadable. A total of 258 (28.5%) had a suspicious nerve, 62 (6.8%) had ocular hypertension, 102 (11.3%) had diabetic retinopathy, and 68 (7.5%) had other retinal abnormalities. CONCLUSION: An integrated telemedicine screening intervention in primary care offices and Federally Qualified Health Centers detected high rate of suspicious optic nerves, ocular hypertension, and retinal pathology.

Lipid signaling and fat storage in the dark-eyed junco.

Seasonal hyperphagia and fattening promote survivorship in migratory and wintering birds, but reduced adiposity may be more advantageous during the breeding season. Factors such as photoperiod, temperature, and food predictability are known environmental determinants of fat storage, but the underlying neuroendocrine mechanisms are less clear. Endocannabinoids and other lipid signaling molecules regulate multiple aspects of energy balance including appetite and lipid metabolism. However, these functions have been established primarily in mammals; thus the role of lipid signals in avian fat storage remains largely undefined. Here we examined relationships between endocannabinoid signaling and individual variation in fat storage in captive white-winged juncos (Junco hyemalis aikeni) following a transition to long-day photoperiods. We report that levels of the endocannabinoid 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), in furcular and abdominal fat depots correlate negatively with fat mass. Hindbrain mRNA expression of CB1 endocannabinoid receptors also correlates negatively with levels of fat, demonstrating that fatter animals experience less central and peripheral endocannabinoid signaling when in breeding condition. Concentrations of the anorexigenic lipid, oleoylethanolamide (OEA), also inversely relate to adiposity. These findings demonstrate unique and significant relationships between adiposity and lipid signaling molecules in the brain and periphery, thereby suggesting a potential role for lipid signals in mediating adaptive levels of fat storage.