Automated Machine Learning for Predicting Diabetic Retinopathy Progression From Ultra-Widefield Retinal Images.

Importance: Machine learning (ML) algorithms have the potential to identify eyes with early diabetic retinopathy (DR) at increased risk for disease progression. Objective: To create and validate automated ML models (autoML) for DR progression from ultra-widefield (UWF) retinal images. Design, Setting and Participants: Deidentified UWF images with mild or moderate nonproliferative DR (NPDR) with 3 years of longitudinal follow-up retinal imaging or evidence of progression within 3 years were used to develop automated ML models for predicting DR progression in UWF images. All images were collected from a tertiary diabetes-specific medical center retinal image dataset. Data were collected from July to September 2022. Exposure: Automated ML models were generated from baseline on-axis 200° UWF retinal images. Baseline retinal images were labeled for progression based on centralized reading center evaluation of baseline and follow-up images according to the clinical Early Treatment Diabetic Retinopathy Study severity scale. Images for model development were split 8-1-1 for training, optimization, and testing to detect 1 or more steps of DR progression. Validation was performed using a 328-image set from the same patient population not used in model development. Main Outcomes and Measures: Area under the precision-recall curve (AUPRC), sensitivity, specificity, and accuracy. Results: A total of 1179 deidentified UWF images with mild (380 [32.2%]) or moderate (799 [67.8%]) NPDR were included. DR progression was present in half of the training set (590 of 1179 [50.0%]). The model's AUPRC was 0.717 for baseline mild NPDR and 0.863 for moderate NPDR. On the validation set for eyes with mild NPDR, sensitivity was 0.72 (95% CI, 0.57-0.83), specificity was 0.63 (95% CI, 0.57-0.69), prevalence was 0.15 (95% CI, 0.12-0.20), and accuracy was 64.3%; for eyes with moderate NPDR, sensitivity was 0.80 (95% CI, 0.70-0.87), specificity was 0.72 (95% CI, 0.66-0.76), prevalence was 0.22 (95% CI, 0.19-0.27), and accuracy was 73.8%. In the validation set, 6 of 9 eyes (75%) with mild NPDR and 35 of 41 eyes (85%) with moderate NPDR progressed 2 steps or more were identified. All 4 eyes with mild NPDR that progressed within 6 months and 1 year were identified, and 8 of 9 (89%) and 17 of 20 (85%) with moderate NPDR that progressed within 6 months and 1 year, respectively, were identified. Conclusions and Relevance: This study demonstrates the accuracy and feasibility of automated ML models for identifying DR progression developed using UWF images, especially for prediction of 2-step or greater DR progression within 1 year. Potentially, the use of ML algorithms may refine the risk of disease progression and identify those at highest short-term risk, thus reducing costs and improving vision-related outcomes.

Bioenergetics of aerobic and anaerobic growth of Shewanella putrefaciens CN32.

Shewanella putrefaciens is a model dissimilatory iron-reducing bacterium that can use Fe(III) and O2 as terminal electron acceptors. Consequently, it has the ability to influence both aerobic and anaerobic groundwater systems, making it an ideal microorganism for improving our understanding of facultative anaerobes with iron-based metabolism. In this work, we examine the bioenergetics of O2 and Fe(III) reduction coupled to lactate oxidation in Shewanella putrefaciens CN32. Bioenergetics were measured directly via isothermal calorimetry and by changes to the chemically defined growth medium. We performed these measurements from 25 to 36°C. Modeling metabolism with macrochemical equations allowed us to define a theoretical growth stoichiometry for the catabolic reaction of 1.00 O2:lactate and 1.33 Fe(III):lactate that was consistent with the observed ratios of O2:lactate (1.20 ± 0.23) and Fe(III):lactate (1.46 ± 0.15) consumption. Aerobic growth showed minimal variation with temperature and minimal variation in thermodynamic potentials of incubation. Fe(III)-based growth showed a strong temperature dependence. The Gibbs energy and enthalpy of incubation was minimized at ≥30°C. Energy partitioning modeling of Fe(III)-based calorimetric incubation data predicted that energy consumption for non-growth associate maintenance increases substantially above 30°C. This prediction agrees with the data at 33 and 35°C. These results suggest that the effects of temperature on Shewanella putrefaciens CN32 are metabolism dependent. Gibbs energy of incubation above 30°C was 3-5 times more exergonic with Fe(III)-based growth than with aerobic growth. We compared data gathered in this study with predictions of microbial growth based on standard-state conditions and based on the thermodynamic efficiency of microbial growth. Quantifying the growth requirements of Shewanella putrefaciens CN32 has advanced our understanding of the thermodynamic constraints of this dissimilatory iron-reducing bacterium.

Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK).

BACKGROUND: An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a ß-lactam-ß-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. METHODS: The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046. FINDINGS: Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam-durlobactam group and 20 (32%) of 62 in the colistin group, a difference of -13·2% (95% CI -30·0 to 3·5), which met criteria for non-inferiority. Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam-durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85). Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam-durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam-durlobactam group and 14 (16%) of 86 patients in the colistin group. INTERPRETATION: Our data show that sulbactam-durlobactam was non-inferior to colistin, both agents given in combination with imipenem-cilastatin, for the primary endpoint of 28-day all-cause mortality. Sulbactam-durlobactam was well tolerated and could be an effective intervention to reduce mortality from serious infections caused by carbapenem-resistant ABC, including multidrug-resistant strains. FUNDING: Entasis Therapeutics and Zai Lab.

Incidence and Progression of Diabetic Retinopathy in American Indian and Alaska Native Individuals Served by the Indian Health Service, 2015-2019.

Importance: Estimates of diabetic retinopathy (DR) incidence and progression in American Indian and Alaska Native individuals are based on data from before 1992 and may not be informative for strategizing resources and practice patterns. Objective: To examine incidence and progression of DR in American Indian and Alaska Native individuals. Design, Setting, and Participants: This was a retrospective cohort study conducted from January 1, 2015, to December 31, 2019, and included adults with diabetes and no evidence of DR or mild nonproliferative DR (NPDR) in 2015 who were reexamined at least 1 time during the 2016 to 2019 period. The study setting was the Indian Health Service (IHS) teleophthalmology program for diabetic eye disease. Exposure: Development of new DR or worsening of mild NPDR in American Indian and Alaska Native individuals with diabetes. Main Outcomes and Measures: Outcomes were any increase in DR, 2 or more (2+) step increases, and overall change in DR severity. Patients were evaluated with nonmydriatic ultra-widefield imaging (UWFI) or nonmydriatic fundus photography (NMFP). Standard risk factors were included. Results: The total cohort of 8374 individuals had a mean (SD) age of 53.2 (12.2) years and a mean (SD) hemoglobin A1c level of 8.3% (2.2%) in 2015, and 4775 were female (57.0%). Of patients with no DR in 2015, 18.0% (1280 of 7097) had mild NPDR or worse in 2016 to 2019, and 0.1% (10 of 7097) had PDR. The incidence rate from no DR to any DR was 69.6 cases per 1000 person-years at risk. A total of 6.2% of participants (441 of 7097) progressed from no DR to moderate NPDR or worse (ie, 2+ step increase; 24.0 cases per 1000 person-years at risk). Of patients with mild NPDR in 2015, 27.2% (347 of 1277) progressed to moderate NPDR or worse in 2016 to 2019, and 2.3% (30 of 1277) progressed to severe NPDR or worse (ie, 2+ step progression). Incidence and progression were associated with expected risk factors and evaluation with UWFI. Conclusions and Relevance: In this cohort study, the estimates of DR incidence and progression were lower than those previously reported for American Indian and Alaska Native individuals. The results suggest extending the time between DR re-evaluations for certain patients in this population, if follow-up compliance and visual acuity outcomes are not jeopardized.

Mineralogy, morphology, and reaction kinetics of ureolytic bio-cementation in the presence of seawater ions and varying soil materials.

Microbially-induced calcium carbonate precipitation (MICP) is a bio-cementation process that can improve the engineering properties of granular soils through the precipitation of calcium carbonate (CaCO3) minerals on soil particle surfaces and contacts. The technology has advanced rapidly as an environmentally conscious soil improvement method, however, our understanding of the effect of changes in field-representative environmental conditions on the physical and chemical properties of resulting precipitates has remained limited. An improved understanding of the effect of subsurface geochemical and soil conditions on process reaction kinetics and the morphology and mineralogy of bio-cementation may be critical towards enabling successful field-scale deployment of the technology and improving our understanding of the long-term chemical permanence of bio-cemented soils in different environments. In this study, thirty-five batch experiments were performed to specifically investigate the influence of seawater ions and varying soil materials on the mineralogy, morphology, and reaction kinetics of ureolytic bio-cementation. During experiments, differences in reaction kinetics were quantified to identify conditions inhibiting CaCO3 precipitation and ureolysis. Following experiments, scanning electron microscopy, x-ray diffraction, and chemical composition analyses were employed to quantify differences in mineralogical compositions and material morphology. Ions present in seawater and variations in soil materials were shown to significantly influence ureolytic activity and precipitate mineralogy and morphology, however, calcite remained the predominant CaCO3 polymorph in all experiments with relative percentages exceeding 80% by mass in all precipitates.

Microbial maintenance energy quantified and modeled with microcalorimetry.

Refining the energetic costs of cellular maintenance is essential for predicting microbial growth and survival in the environment. Here, we evaluate a simple batch culture method to quantify energy partitioning between growth and maintenance using microcalorimetry and thermodynamic modeling. The constants derived from the batch culture system were comparable to those that have been reported from meta-analyses of data derived from chemostat studies. The model accurately predicted temperature-dependent biomass yield and the upper temperature limit of growth for Desulfovibrio alaskensis G20, suggesting the method may have broad application. An Arrhenius temperature dependence for the specific energy consumption rate, inferred from substrate consumption and heat evolution, was observed over the entire viable temperature range. By combining this relationship for specific energy consumption rates and observed specific growth rates, the model describes an increase in nongrowth associated maintenance at higher temperatures and the corresponding decrease in energy available for growth. This analytical and thermodynamic formulation suggests that simply monitoring heat evolution in batch culture could be a useful complement to the recognized limitations of estimating maintenance using extrapolation to zero growth in chemostats.

Cost impact of hydroxocobalamin in the treatment of patients with known or suspected cyanide poisoning due to smoke inhalation from closed-space fires.

BACKGROUND & OBJECTIVES: Cyanide poisoning can occur due to exposure to smoke in closed-space fires. With no point of care cyanide test at the scene of a fire, first responders and clinicians base decisions to treat with cyanide antidote on patient history, clinical signs, and other indirect data points that have not been proven to correspond with actual systemic levels of cyanide. The aim of this exploratory study was to determine the economic implications of treating patients with known or suspected cyanide poisoning due to smoke inhalation with hydroxocobalamin. METHODS: A decision analysis model was developed from the US hospital perspective. Healthcare resource utilization was estimated from a retrospective evaluation of clinical outcomes in hydroxocobalamin-treated patients and in historical controls without hydroxocobalamin use (Nguyen, et al. 2017). Epidemiologic parameters and costs were estimated from the published literature, and publicly-available hospital charges were identified. Outcomes reported in the analysis included expected healthcare resource utilization in the US population and per-patient costs with and without the use of hydroxocobalamin. A cost-to-charge ratio was applied so that all costs would reflect hospital costs rather than hospital charges. Deterministic sensitivity analysis was performed to identify the most influential model parameters. All costs were reported in 2017 US dollars. RESULTS: Use of hydroxocobalamin reduces healthcare resource utilization and contributes to decreased per-patient hospital costs ($15,381 with hydroxocobalamin treatment versus $22,607 with no cyanide antidote). The most substantive cost-savings resulted from decreased hospital length of stay (i.e., intensive care unit [ICU] and non-ICU). Costs attributed to mechanical ventilation also decreased with use of hydroxocobalamin. A univariate sensitivity analysis demonstrated that the most impactful variables in the cost analysis were related to hospital length of stay (ICU followed by non-ICU stay), followed by the daily cost of ICU stay. CONCLUSIONS: Use of hydroxocobalamin in patients with known or suspected cyanide poisoning from closed-space fire smoke inhalation may decrease hospital costs and contribute to more efficient healthcare resource utilization.

Prevalence of Diabetic Eye Diseases in American Indians and Alaska Natives (AI/AN) as Identified by the Indian Health Service's National Teleophthalmology Program Using Ultrawide Field Imaging (UWFI).

PURPOSE: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services' (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI). METHODS: This was a retrospective analysis of 2016-2019 clinical data (n = 53,900). UWF images were acquired by certified imagers using a validated protocol, and graded by licensed, certified optometrists supervised by an ophthalmologist. Graders evaluated the extent/severity of retinal lesions in comparison to standard photographs. DR lesions predominantly in any peripheral field were considered "predominantly peripheral lesions" (PPL). The analyses calculated prevalence of any DR, any DME, DR and DME severity, sight-threatening disease, and PPL. RESULTS: Patients averaged 56 years of age with a 68 mmol/mol A1c and 55% had had diabetes for 5+ years. Prevalence of any DR, any DME, and sight-threatening disease was 28.6%, 3.0%, and 3.0%. In patients with mild nonproliferative DR, PPL was seen in 25.3%. PPL suggested a more severe level of DR in 8.7% of patients. DR increased with age. DME decreased with age. Males and patients in the Nashville IHS area had more diabetic eye disease. CONCLUSION: AI/AN have a high burden of diabetes and its complications. The IHS is resource-constrained, making accurate disease estimates necessary for resource allocation and budget justifications to Congress. These data update the estimates of diabetic eye disease in Indian Country and suggest that UWFI identifies early DR.

Fostering Cognitive Presence, Social Presence and Teaching Presence with Integrated Online-Team-Based Learning.

This paper describes the development of the Integrated Online-Team-Based Learning (IO-TBL) model and details students' perceptions of IO-TBL using the Community of Inquiry framework. IO-TBL is an online team-based learning course design that combines the flexibility of asynchronous engagement with the connectedness offered through synchronous meetings. Student comments from small group instructional feedback sessions and end-of-course teaching evaluations were grouped into clusters of similar statements about what was going well and suggestions for improvement, which were then assigned to one of the three presences of the Community of Inquiry framework. While students most commonly identified increased learning, synchronous meetings, teamwork, and the instructor as going well in the course, students found IO-TBL to impose a heavy workload and require a significant amount of time. Clusters were most often related to teaching presence, followed by social presence, and then cognitive presence.

Energetics of Acidianus ambivalens growth in response to oxygen availability.

All life requires energy to drive metabolic reactions such as growth and cell maintenance; therefore, fluctuations in energy availability can alter microbial activity. There is a gap in our knowledge concerning how energy availability affects the growth of extreme chemolithoautotrophs. Toward this end, we investigated the growth of thermoacidophile Acidianus ambivalens during sulfur oxidation under aerobic to microaerophilic conditions. Calorimetry was used to measure enthalpy (ΔHinc ) of microbial activity, and chemical changes in growth media were measured to calculate Gibbs energy change (ΔGinc ) during incubation. In all experiments, Gibbs energy was primarily dissipated through the release of heat, which suggests enthalpy-driven growth. In microaerophilic conditions, growth was significantly more efficient in terms of biomass yield (defined as C-mol biomass per mole sulfur consumed) and resulted in lower ΔGinc and ΔHinc . ΔGinc in oxygen-limited (OL) and oxygen- and CO2 -limited (OCL) microaerophilic growth conditions resulted in averages of -1.44 × 103  kJ/C-mol and -7.56 × 102  kJ/C-mol, respectively, and average ΔHinc values of -1.11 × 105  kJ/C-mol and -4.43 × 104  kJ/C-mol, respectively. High-oxygen experiments resulted in lower biomass yield values, an increase in ΔGinc to -1.71 × 104  kJ/C-mol, and more exothermic ΔHinc values of -4.71 × 105  kJ/C-mol. The observed inefficiency in high-oxygen conditions may suggest larger maintenance energy demands due to oxidative stresses and a preference for growth in microaerophilic environments.

Comparing demographics of signatories to public letters on diversity in the mathematical sciences.

In its December 2019 edition, the Notices of the American Mathematical Society published an essay critical of the use of diversity statements in academic hiring. The publication of this essay prompted many responses, including three public letters circulated within the mathematical sciences community. Each letter was signed by hundreds of people and was published online, also by the American Mathematical Society. We report on a study of the signatories' demographics, which we infer using a crowdsourcing approach. Letter A highlights diversity and social justice. The pool of signatories contains relatively more individuals inferred to be women and/or members of underrepresented ethnic groups. Moreover, this pool is diverse with respect to the levels of professional security and types of academic institutions represented. Letter B does not comment on diversity, but rather, asks for discussion and debate. This letter was signed by a strong majority of individuals inferred to be white men in professionally secure positions at highly research intensive universities. Letter C speaks out specifically against diversity statements, calling them "a mistake," and claiming that their usage during early stages of faculty hiring "diminishes mathematical achievement." Individuals who signed both Letters B and C, that is, signatories who both privilege debate and oppose diversity statements, are overwhelmingly inferred to be tenured white men at highly research intensive universities. Our empirical results are consistent with theories of power drawn from the social sciences.

The Indian Health Service Primary Care-Based Teleophthalmology Program for Diabetic Eye Disease Surveillance and Management.

Background: Historically, fewer than half of American Indians and Alaska Natives (AI/AN) with diabetes received the annual diabetic retinopathy (DR) examination that is considered the minimum standard of care; this rate is similar to that of the general United States (U.S.) population with diabetes. Solution: The Indian Health Service-Joslin Vision Network (IHS-JVN) Teleophthalmology Program in 2000 to increase compliance with DR standards of care among AI/AN through validated, primary care-based telemedicine. The IHS-JVN provides remote diagnosis of DR severity, with a report including management recommendations that is returned to the patient's primary care provider. The program conforms with the American Telemedicine Association (ATA) Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy. Outcomes: The IHS-JVN has been expanding incrementally since the first patients were recruited in 2000; this expansion coincides with large improvements in the annual DR examination rates reported as part of local, regional, and national regulatory compliance under the Government Performance and Results Act (GPRA). Currently, with 99 clinical implementations in 23 states, IHS-JVN is the largest primary care-based ATA validation category three telemedicine program in the U.S. Summary: This article describes the program's workflow, imaging and reading technologies, diagnostic protocols, reports to providers, training, quality assurance processes, and geographical distribution. In addition to its clinical use, the program has been utilized in research on utilization of diabetic eye care, cost-effectiveness, technology development, and DR epidemiology of the AI/AN population. Potential next steps for this program are discussed.

Magnesium isotope fractionation during microbially enhanced forsterite dissolution.

Bacillus subtilis endospore-mediated forsterite dissolution experiments were performed to assess the effects of cell surface reactivity on Mg isotope fractionation during chemical weathering. Endospores present a unique opportunity to study the isolated impact of cell surface reactivity because they exhibit extremely low metabolic activity. In abiotic control assays, 24 Mg was preferentially released into solution during forsterite dissolution, producing an isotopically light liquid phase (δ26 Mg = -0.39 ± 0.06 to -0.26 ± 0.09‰) relative to the initial mineral composition (δ26 Mg = -0.24 ± 0.03‰). The presence of endospores did not have an apparent effect on Mg isotope fractionation associated with the release of Mg from the solid into the aqueous phase. However, the endospore surfaces preferentially adsorbed 24 Mg from the dissolution products, which resulted in relatively heavy aqueous Mg isotope compositions. These aqueous Mg isotope compositions increased proportional to the fraction of dissolved Mg that was adsorbed, with the highest measured δ26 Mg (-0.08 ± 0.07‰) corresponding to the highest degree of adsorption (~76%). The Mg isotope composition of the adsorbed fraction was correspondingly light, at an average δ26 Mg of -0.49‰. Secondary mineral precipitation and Mg adsorption onto secondary minerals had a minimal effect on Mg isotopes at these experimental conditions. Results demonstrate the isolated effects of cell surface reactivity on Mg isotope fractionation separate from other common biological processes, such as metabolism and organic acid production. With further study, Mg isotopes could be used to elucidate the role of the biosphere on Mg cycling in the environment.

Mechanisms of the Removal of U(VI) from Aqueous Solution Using Biochar: A Combined Spectroscopic and Modeling Approach.

Biochar has been touted as a promising sorbent for the removal of inorganic contaminants, such as uranium (U), from water. However, the molecular-scale mechanisms of aqueous U(VI) species adsorption to biochar remain poorly understood. In this study, two approaches, grounded in equilibrium thermodynamics, were employed to investigate the U(VI) adsorption mechanisms: (1) batch U(VI) adsorption experiments coupled to surface complexation modeling (SCM) and (2) isothermal titration calorimetry (ITC), supported by synchrotron-based X-ray absorption spectroscopy (XAS) analyses. The biochars tested have considerable proton buffering capacity and most strongly adsorb U(VI) between approximately pH 4 and 6. FT-IR and XPS studies, along with XAS analyses, show that U(VI) adsorption occurs primarily at the proton-active carboxyl (-COOH) and phenolic hydroxyl (-OH) functional groups on the biochar surface. The SCM approach is able to predict U(VI) adsorption behavior across a wide range of pH and at varying initial U(VI) and biochar concentrations, and U adsorption is strongly influenced by aqueous U(VI) speciation. Supporting ITC measurements indicate that the calculated enthalpies of protonation reactions of the studied biochar, as well as the adsorption of U(VI), are consistent with anionic oxygen ligands and are indicative of both inner- and outer-sphere complexation. Our results provide new insights into the modes of U(VI) adsorption by biochar and more generally improve our understanding of its potential to remove radionuclides from contaminated waters.

Prevalence of diabetic retinopathy and diabetic macular edema in a primary care-based teleophthalmology program for American Indians and Alaskan Natives.

BACKGROUND: Diabetes and its complications are more common in American Indians and Alaska Natives (AI/AN) than other US racial/ethnic populations. Prior reports of diabetic retinopathy (DR) prevalence in AI/AN are dated, and research on diabetic macular edema (DME) is limited. This study characterizes the recent prevalence of DR and DME in AI/AN using primary care-based teleophthalmology surveillance. METHODS: This is a multi-site, clinic-based, cross-sectional study of DR and DME. The sample is composed of AI /AN patients with diabetes (n = 53,998), served by the nationally distributed Indian Health Service-Joslin Vision Network Teleophthalmology Program (IHS-JVN) in primary care clinics of US Indian Health Service (IHS), Tribal, and Urban Indian health care facilities (I/T/U) from 1 November 2011 to 31 October 2016. Patients were recruited opportunistically for a retinal examination using the IHS-JVN during their regular diabetes care. The IHS-JVN used clinically validated, non-mydriatic, retinal imaging and retinopathy assessment protocols to identify the severity levels of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), DME, and sight threatening retinopathy (STR; a composite measure). Key social-demographic (age, gender, IHS area), diabetes-related health (diabetes therapy, duration of diabetes, A1c), and imaging technology variables were examined. The analysis calculated frequencies and percentages of severity levels of disease. RESULTS: Prevalence of any NPDR, PDR, DME, and STR among AI/AN patients undergoing DR teleophthalmology surveillance by IHS-JVN was 17.7%, 2.3%, 2.3%, and 4.2%, respectively. Prevalence was lowest in Alaska and highest among patients with A1c >/ = 8%, duration of diabetes > 10 years, or using insulin. CONCLUSIONS: Prevalence of DR in this cohort was approximately half that in previous reports for AI/AN, and prevalence of DME was less than that reported in non-AI/AN populations. A similar reduction in diabetes related end-stage renal disease in the same population and time period has been reported by other researchers. Since these two diabetic complications share a common microvasculopathic mechanism, this coincident change in prevalence may also share a common basis, possibly related to improved diabetes management.

Thermodynamic Analysis of Nickel(II) and Zinc(II) Adsorption to Biochar.

While numerous studies have investigated metal uptake from solution by biochar, few of these have developed a mechanistic understanding of the adsorption reactions that occur at the biochar surface. In this study, we explore a combined modeling and spectroscopic approach for the first time to describe the molecular level adsorption of Ni(II) and Zn(II) to five types of biochar. Following thorough characterization, potentiometric titrations were carried out to measure the proton (H+) reactivity of each biochar, and the data was used to develop protonation models. Surface complexation modeling (SCM) supported by synchrotron-based extended X-ray absorption fine structure (EXAFS) was then used to gain insights into the molecular scale metal-biochar surface reactions. The SCM approach was combined with isothermal titration calorimetry (ITC) data to determine the thermodynamic driving forces of metal adsorption. Our results show that the reactivity of biochar toward Ni(II) and Zn(II) directly relates to the site densities of biochar. EXAFS along with FT-IR analyses, suggest that Ni(II) and Zn(II) adsorption occurred primarily through proton-active carboxyl (-COOH) and hydroxyl (-OH) functional groups on the biochar surface. SCM-ITC analyses revealed that the enthalpies of protonation are exothermic and Ni(II) and Zn(II) complexes with biochar surface are slightly exothermic to slightly endothermic. The results obtained from these combined approaches contribute to the better understanding of molecular scale metal adsorption onto the biochar surface, and will facilitate the further development of thermodynamics-based, predictive approaches to biochar removal of metals from contaminated water.