Watershed analysis of urban stormwater contaminant 6PPD-Quinone hotspots and stream concentrations using a process-based ecohydrological model.

Coho salmon (Oncorhynchus kisutch) are highly sensitive to 6PPD-Quinone (6PPD-Q). Details of the hydrological and biogeochemical processes controlling spatial and temporal dynamics of 6PPD-Q fate and transport from points of deposition to receiving waters (e.g., streams, estuaries) are poorly understood. To understand the fate and transport of 6PPD and mechanisms leading to salmon mortality Visualizing Ecosystem Land Management Assessments (VELMA), an ecohydrological model developed by US Environmental Protection Agency (EPA), was enhanced to better understand and inform stormwater management planning by municipal, state, and federal partners seeking to reduce stormwater contaminant loads in urban streams draining to the Puget Sound National Estuary. This work focuses on the 5.5 km2 Longfellow Creek upper watershed (Seattle, Washington, United States), which has long exhibited high rates of acute urban runoff mortality syndrome in coho salmon. We present VELMA model results to elucidate these processes for the Longfellow Creek watershed across multiple scales-from 5-m grid cells to the entire watershed. Our results highlight hydrological and biogeochemical controls on 6PPD-Q flow paths, and hotspots within the watershed and its stormwater infrastructure, that ultimately impact contaminant transport to Longfellow Creek and Puget Sound. Simulated daily average 6PPD-Q and available observed 6PPD-Q peak in-stream grab sample concentrations (ng/L) corresponds within plus or minus 10 ng/L. Most importantly, VELMA's high-resolution spatial and temporal analysis of 6PPD-Q hotspots provides a tool for prioritizing the locations, amounts, and types of green infrastructure that can most effectively reduce 6PPD-Q stream concentrations to levels protective of coho salmon and other aquatic species.

High hydroxyurea usage in sickle cell anemia regardless of patient demographics.

Hydroxyurea is highly effective in sickle cell disease, but it is still underutilized. Reports of hydroxyurea utilization largely use Medicaid data, and socioeconomics is often cited as a barrier. To address whether patient demographics influenced the high hydroxyurea usage rate recently reported for the pediatric sickle cell program of Northern Virginia, analysis of data from 2011 to 2021 revealed no statistical difference in hydroxyurea usage rate between Medicaid and non-Medicaid, African American and African, or age less than 13 and age greater than or equal to 13 years cohorts, demonstrating that hydroxyurea can be successfully implemented across demographic groups.

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

BACKGROUND: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. METHODS: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. RESULTS: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. CONCLUSION: In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

Role of the valuation of nervousness in cortisol responses to psychosocial stress task and task performance in European American and East Asian students.

How people perceive and value negative affective states is associated with physiological responses to stressful events and moderates the association between negative feelings and physiological and behavioral outcomes. However, previous studies on valuation of negative affective states have been conducted mostly in Western cultures. Different cultural backgrounds shape how people view negative emotions as well as how people attend to internal emotional states, which may change the effects of valuing negative emotions. The present study thus examined whether valuation of nervousness was associated with the magnitude and duration of cortisol responses to a standardized laboratory stressor and task performance in East Asian and European American students. Two hundred undergraduate students were recruited through a large pool of students taking psychology courses. They engaged in demanding speech and arithmetic tasks as part of the Trier Social Stress Test (TSST). European American participants who had a higher valuation of nervousness showed lower cortisol reactivity. Valuing nervousness was associated with better speech performance in students from both cultural backgrounds, and the strength of this association was moderated by cortisol level. Our findings call attention to the importance of considering whether negative emotions are viewed as beneficial or an impediment, as well as the cultural context when responding to demanding and threatening situations.

Improved urban runoff prediction using high-resolution land-use, imperviousness, and stormwater infrastructure data applied to a process-based ecohydrological model.

Modeling large-scale hydrological impacts brought about by site-level green and gray stormwater remediation actions is difficult because urbanized areas are extremely complex dynamic landscapes that include engineered features that, by design, expedite urban runoff to streams, creeks, and other water bodies to reduce urban flooding during storm events. Many urban communities use heavily engineered gray infrastructure to achieve that goal, along with more recent additions of green infrastructure such as rain gardens, bioswales, and riparian corridors. Therefore, successfully characterizing those design details and associated management practices, interactions, and impacts requires a detailed understanding of how fine and course-scale hydrologic processes and routing are altered and managed in urban watersheds. To enhance hydrologic modeling capabilities of urban watersheds, we implemented a number of improvements to an existing ecohydrology model called VELMA-Visualizing Ecosystem Land Management Assessments-including the addition of spatially explicit engineered features that impact urban hydrology (e.g., impervious surfaces, curbed roadways, stormwater routing) and refinement to the computational representations of evapotranspiration by adding impervious surface evaporation. We demonstrate improved capabilities for modeling within complex urbanized watersheds by simulating stream runoff within the Longfellow Creek watershed, City of Seattle, Washington (WA), United States (US) with and without these added urban watershed characteristics. The results demonstrate that the newly improved VELMA model allows for more accurate modeling of hydrology within urban watersheds. Being a fate and transport ecohydrology model, the improved hydrologic flow enhances VELMA's current capacity for modeling nutrient, contaminant, and thermal loadings.

Ten-year longitudinal analysis of hydroxyurea implementation in a pediatric sickle cell program.

Hydroxyurea (HU) has proven benefit in sickle cell anemia (SCA), but HU is still underutilized. The Pediatric Sickle Cell Program of Northern Virginia prescribes HU regardless of symptoms to all SCA patients age ≥ 9 months and prospectively tracks outcomes. HU is dosed to maximum tolerated dosing (MTD), targeting 30% Hgb F. Longitudinal data from 2009 to 2019 encompassing 1222 HU-eligible and 950 HU-exposure patient-years were analyzed in 2-year intervals for hemoglobin (Hgb), fetal hemoglobin (Hgb F), hospitalizations, transfusions, and treat-and-release ED visits. Comparing HU-eligible patients in the interval prior to HU implementation (2009-2011) to the last interval analyzed after HU implementation (2017-2019), HU usage increased from 33% to 93%, average Hgb increased from 8.3 ± 0.98 to 9.8 ± 1.3 g/dl (p < .0001), average Hgb F rose from 13 ± 8.7% to 26 ± 9.9% (p < .0001), hospitalizations decreased from 0.71 (95% CI 0.54-0.91) to 0.2 (95% CI 0.13-0.28) admissions/person-year, sporadic transfusions decreased from 0.4 (95% CI 0.27-0.55) to 0.05 (95% CI 0.02-0.12) transfusions/person-year. Treat-and-release ED visit rates remained unchanged, varying between 0.49 (95% CI 0.36-0.64) and 0.64 (95% CI 0.48-0.83) visits/person-year. By the last interval, 72% of patients had Hgb ≥ 9 g/dl, 42% had Hgb F ≥ 30%, 79% experienced no hospitalizations, and 94% received no transfusions. Uniform HU prescription for SCA patients with close monitoring to achieve high Hgb F resulted in significant improvements in laboratory and clinical outcomes within 2 years, which continued to improve over the next 6 years. Rigorous HU implementation in a pediatric sickle cell population is feasible, effective, and sustainable.

Second-generation corneal deformation signal waveform analysis in normal, forme fruste keratoconic, and manifest keratoconic corneas after statistical correction for potentially confounding factors.

PURPOSE: To evaluate the difference in corneal biomechanical waveform parameters between manifest keratoconus, forme fruste keratoconus, and healthy eyes with a second-generation biomechanical waveform analyzer (Ocular Response Analyzer 2). SETTING: Jules Stein Eye Institute, University of California, Los Angeles, California, USA. DESIGN: Retrospective chart review. METHODS: The biomechanical waveform analyzer was used to obtain corneal hysteresis (CH), corneal resistance factor (CRF), and 37 biomechanical waveform parameters in manifest keratoconus eyes, forme fruste keratoconus eyes, and healthy eyes. Useful distinguishing parameters were found using t tests and a multivariable logistic regression model with stepwise variable selection. Potential confounders were controlled for. RESULTS: The study included 68 manifest keratoconus eyes, 64 forme fruste keratoconus eyes, and 249 healthy eyes. There was a statistical difference in the mean CRF between the normal group (10.2 mm Hg ± 1.7 [SD]) and keratoconus group (6.3 ± 1.9 mm Hg) (P = .003), and between the normal group and the forme fruste keratoconus group (7.8 ± 1.4 mm Hg) (P < .0001). There was no statistical difference in the mean CH between the normal group and the keratoconus group or the forme fruste keratoconus group. The CRF, height of peak 1 (P1) (P = .001), downslope of P1 (dslope1) (P = .027), upslope of peak 2 (P2) (P = .004), and downslope of P2 (P = .006) distinguished the normal group from the keratoconus groups. The CRF, downslope of P2 derived from upper 50% of applanation peak (P = .035), dslope1 (P = .014), and upslope of P1 (P = .008) distinguished the normal group from the forme fruste keratoconus group. CONCLUSION: Differences in multiple biomechanical waveform parameters can differentiate between healthy and diseased conditions and might improve early diagnosis of keratoconus and forme fruste keratoconus. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Bitoric rigid gas permeable contact lenses in the optical management of penetrating keratoplasty.

PURPOSE: The purpose of this study was to evaluate the complexity and effectiveness of fitting bitoric rigid gas permeable contact lenses (RGPCLs), compared to spherical RGPCLS, when used in the correction of high amounts of post-penetrating keratoplasty astigmatism. METHODS: Records of post-penetrating keratoplasty (PKP) patients being managed with bitoric RGPCLs were compared to controls (post-PKP patients managed with spherical RGPCLs). Factors that were analyzed included the number of diagnostic RGPCLs used to assess the initial fit, the number of RGPCLs ordered to finalize the fit and the number of total doctor visits to finalize the fit. RESULTS: Fourteen eyes of 14 patients satisfied the study criteria. The average amount of total astigmatism in this study group was 10.0D±5.0 compared to the control group which was 3.3D±2.6. The number of diagnostic RGPCLs used for the study group was 1.2±0.4 compared to 1.0±0.0 for the control group. The mean number of contact lenses ordered to complete the fitting for the study group was 1.9±0.7 compared to the control which was 2.1±0.8. The study group presented for an average of 6.3±1.6 visits whereas the control group presented for 4.9±1.1 visits. Contact lens corrected acuity for the study group was 0.101±0.11 (20/25) compared to the control group 0.08±0.12 (20/24). CONCLUSIONS: The complexity of fitting bitoric RGPCLs was found to be similar to fitting spherical RGPCLs on post-PKP eyes and the visual outcomes were not different.