Cost-effectiveness Analysis of a Personalized, Teleretinal-Inclusive Screening Policy for Diabetic Retinopathy via Markov Modeling.

PURPOSE: Although teleretinal imaging has proved effective in increasing population-level screening for diabetic retinopathy (DR), there is a lack of quantitative understanding of how to incorporate teleretinal imaging into existing screening guidelines. We develop a mathematical model to determine personalized DR screening recommendations that utilize teleretinal imaging and evaluate the cost-effectiveness of the personalized screening policy. DESIGN: A partially observable Markov decision process is employed to determine personalized screening recommendations based on patient compliance, willingness to pay, and A1C level. Deterministic sensitivity analysis was conducted to evaluate the impact of patient-specific factors on personalized screening policy. The cost-effectiveness of identified screening policies was evaluated via hidden-Markov chain Monte Carlo simulation on a data-based hypothetical cohort. PARTICIPANTS: Screening policies were simulated for a hypothetical cohort of 500 000 patients with parameters based on the literature and electronic medical records of 2457 patients who received teleretinal imaging from 2013 to 2020 from the Harris Health System. METHODS: Population-based mathematical modeling study. Interventions included dilated fundus examinations referred to as clinical screening, teleretinal imaging, and wait and watch recommendations. MAIN OUTCOME MEASURES: Personalized screening recommendations based on patient-specific factors. Accumulated quality-adjusted life-years (QALYs) and cost (USD) per patient under different screening policies. Incremental cost-effectiveness ratio to compare different policies. RESULTS: For the base cohort, on average, teleretinal imaging was recommended 86.7% of the time over each patient's lifetime. The model-based personalized policy dominated other standardized policies, generating more QALY gains and cost savings for at least 57% of the base cohort. Similar outcomes were observed in sensitivity analyses of the base cohort and the Harris Health-specific cohort and rural population scenario analysis. CONCLUSIONS: A mathematical model was developed as a decision support tool to identify a personalized screening policy that incorporates both teleretinal imaging and clinical screening and adapts to patient characteristics. Compared with current standardized policies, the model-based policy significantly reduces costs, whereas it is performing comparably, if not better, in terms of QALY gain. A personalized approach to DR screening has significant potential benefits that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Mitigation of harmful chemical formation from pyrolysis of tobacco waste using CO2.

Global consumption of tobacco has been continuously increasing. This results in the considerable generation of toxic waste materials from the tobacco industry and daily life. Conventional disposal methods for them (incineration and landfilling) could be a potential hazard for releasing carcinogens and toxins into our eco-system. Accordingly, an eco-friendly disposal platform for converting tobacco waste (TW) into syngas was mainly studied in this present work. To realize this, pyrolysis of two commercial cigarette products (Marlboro and HEETS (electronic cigarette)) was done under the CO2/N2 conditions. One of the main findings from the present study was that CO2 reacted with volatile matters (VMs) obtained from the thermolysis of TW through the gas phase reactions (GPRs), which provided a strategic measure to manipulate carbon rearrangement of all pyrolysates. In particular, the GPRs expedited the carbon rearrangement of harmful chemical species, converting toxic chemicals into syngas. When the fraction of VMs in TWs increased, the GPR were more effective. Therefore, the introduced eco-friendly method using CO2-mediated thermochemical process could be beneficial for energy recovery from TWs while mitigating the formations of harmful chemical species.

Association between urinary polycyclic aromatic hydrocarbons and hypertension in the Korean population: data from the Second Korean National Environmental Health Survey (2012-2014).

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational pollutants derived from incomplete combustion of organic materials, including wood and fossil fuels. Epidemiological studies have evaluated the association between PAH exposure and hypertension or cardiovascular disease in the general population, but the evidence is limited. In this study, we evaluated the association between urinary PAH metabolites and hypertension in the Korean adult population. A total of 6478 adults who participated in the Second Korean National Environmental Health Survey (2012-2014) were included. The differences in urinary concentrations of four PAH metabolites, including 1-hydroxypyrene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 2-naphthol, were compared according to hypertension status using a general linear model. Adjusted odds ratios (aORs) for hypertension were calculated according to the quartile groups of urinary PAH metabolites after adjusting for age, sex, body mass index (BMI), smoking, and alcohol consumption in multiple logistic regression analyses. The estimated mean concentrations of urinary 1-hydroxyphenanthrene were significantly higher in the hypertension group than in the non-hypertension group. In 1-hydroxyphenanthrene, the OR for hypertension was significantly higher in the third and fourth quartile groups than in the first quartile group (third: OR 1.707, 95% CI 1.203-2.423, fourth: OR 1.604, 95% CI 1.158-2.223). No significant associations were detected for the other metabolites. Our results suggest an association between exposure to PAHs and hypertension in a Korean adult population. Further studies are required to evaluate the effects of low-dose long-term exposure to PAHs on hypertension and cardiovascular disease.

Electroplated Silver-Nickel Core-Shell Nanowire Network Electrodes for Highly Efficient Perovskite Nanoparticle Light-Emitting Diodes.

The low sheet resistance and high optical transparency of silver nanowires (AgNWs) make them a promising candidate for use as the flexible transparent electrode of light-emitting diodes (LEDs). In a perovskite LED (PeLED), however, the AgNW electrode can react with the overlying perovskite material by redox reactions, which limit the electroluminescence efficiency of the PeLED by causing the degradation of and generating defect states in the perovskite material. In this study, we prepared Ag-Ni core-shell NW electrodes using the solution-electroplating technique to realize highly efficient PeLEDs based on colloidal formamidinium lead bromide (FAPbBr3) nanoparticles (NPs). Solvated Ni ions from the NiSO4 source were deposited onto the surface of AgNW networks in three steps: (i) cathodic cleaning, (ii) adsorption of the Ni-ion complex onto the AgNW surface, and (iii) uniform electrodeposition of Ni. An ultrathin (∼3.5 nm) Ni layer was uniformly deposited onto the AgNW surface, which exhibited a sheet resistance of 16.7 Ω/sq and an optical transmittance of 90.2%. The Ag-Ni core-shell NWs not only increased the work function of the AgNW electrode, which facilitated hole injection into the emitting layer, but also suppressed the redox reaction between Ag and FAPbBr3 NPs, which prevented the degradation of the emitting layer and the generation of defect states in it. The resulting PeLEDs based on FAPbBr3 NPs with the Ag-Ni core-shell NWs showed high current efficiency of 44.01 cd/A, power efficiency of 35.45 lm/W, and external quantum efficiency of 9.67%.

Catalytic Pyrolysis of Polystyrene over Steel Slag under CO2 Environment.

As the consumption of plastic materials has been dramatically increased, the abundant presence of their debris has become a significant problem worldwide. Thus, this study proposes a sustainable plastic conversion platform for energy recovery. In detail, polystyrene pyrolysis was examined as a case study under CO2 atmosphere in reference to N2 condition. The major gaseous and liquid products from polystyrene pyrolysis include permanent gases (syngas and C1-2 hydrocarbons) and condensable aromatic compounds. Under CO2 environment, the reduction of polycyclic aromatic hydrocarbons (PAHs) was achieved during polystyrene pyrolysis, in comparison with N2 condition. Since its slow reaction kinetics, conversion of condensable hydrocarbons into permanent gases was not fully activated. Therefore, a cheap industrial waste, steel slag (SS), was employed as a catalyst to increase reaction kinetics. The synergistic effects of SS and CO2 contributed to doubling H2 production, while CO formation increased more than 300 times, in reference to non-catalytic pyrolysis. Because CO2 acted as an oxidant for CO production, control of H2/CO ratio was achieved in different conditions. Thus, the utilization of CO2 would suggest a promising way to reduce the formation of PAHs, adopting the reliable platform to produce syngas from plastic waste.

Synthesis of nickel/biochar composite from pyrolysis of Microcystis aeruginosa and its practical use for syngas production.

This study proposes a sustainable waste-to-energy/biochar platform using a toxic microalgal biomass waste. In particular, CO2-feeding pyrolysis of Microcystis aeruginosa (M. aeruginosa) waste was investigated, focusing on the analysis of gaseous pyrolysates and properties of biochar with a construction of mass balance. Also, the catalytic capability of biochar produced from M. aeruginosa was explored to reinforce the mechanistic impact of CO2 on the pyrolysis process within the overall process level. Ni impregnated biochar composite was further synthesized and used as a catalyst to promote syngas formation in the CO2-feeding pyrolysis process of M. aeruginosa.

The effects of exposure to lead, cadmium and mercury on follicle-stimulating hormone levels in men and postmenopausal women: data from the Second Korean National Environmental Health Survey (2012-2014).

BACKGROUND: Follicle-stimulating hormone (FSH), a gonadotropin secreted by the pituitary gland, is a representative secondary sex hormone and an important indicator of reproductive function. The effects of heavy metals such as lead, cadmium, and mercury on humans have been studied, but reports on their effects on sex hormone levels are lacking. Therefore, we investigated the relationship between heavy metal exposure and FSH levels in Korean men and postmenopausal women. METHODS: A total of 4,689 adults (2,763 men and 1,926 postmenopausal women aged 50 years or over) who participated in the Second Korean National Environmental Health Survey (2012-2014) were included. We compared differences in serum FSH levels by demographic characteristics using the t-test and analysis of variance. Multiple linear regression analysis was used to determine the relationship between the blood levels of lead and mercury and the urine cadmium level, and serum FSH levels. RESULTS: On multiple linear regression analysis, lead exposure was positively associated with serum FSH concentrations in postmenopausal women (ß = 2.929, p = 0.019). However, we found no significant association between serum FSH concentration and blood lead and mercury levels, or urine cadmium level, in men. CONCLUSIONS: This study suggests that lead exposure can affect the FSH level in postmenopausal women. Further studies are needed to evaluate the effects of low-dose long-term exposure to heavy metals on sex hormones.

Biodiesel synthesis using chicken manure biochar and waste cooking oil.

This study laid an emphasis on the possible employment of biochar generated from pyrolysis of chicken manure to establish a green platform for producing biodiesel. To this end, the pseudo-catalytic transesterification reaction using chicken manure biochar and waste cooking oil was investigated. Compared with a commercial porous material (SiO2), chicken manure biochar generated from 350°C showed better performance, resulting in 95.6% of the FAME yield at 350°C. The Ca species in chicken manure biochar imparted strong catalytic capability by providing the basicity for transesterification. The identified catalytic effect also led to the thermal cracking of unsaturated FAMEs, which decreased the overall FAME yield. For example, 40-60% of converted FAMEs were thermally degraded. To avoid undesirable thermal cracking arising from the high content of the Ca species in chicken manure biochar, the fabrication of chicken manure biochar at temperatures ≥350°C was highly recommended.

Models for predicting objective function weights in prostate cancer IMRT.

PURPOSE: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer. METHODS: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and applied three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated. RESULTS: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics. CONCLUSIONS: The authors demonstrated that the KNN and MLR weight prediction methodologies perform comparably to the LR model and can produce clinical quality treatment plans by simultaneously predicting multiple weights that capture trade-offs associated with sparing multiple OARs.

Real-Time Analysis of Cellular Response to Small-Molecule Drugs within a Microfluidic Dielectrophoresis Device.

Quantitative detection of the biological properties of living cells is essential for a wide range of purposes, from the understanding of cellular characteristics to the development of novel drugs in nanomedicine. Here, we demonstrate that analysis of cell biological properties within a microfluidic dielectrophoresis device enables quantitative detection of cellular biological properties and simultaneously allows large-scale measurement in a noise-robust and probeless manner. Applying this technique, the static and dynamic biological responses of live B16F10 melanoma cells to the small-molecule drugs such as N-ethylmaleimide (NEM) and [(dihydronindenyl)oxy]alkanoic acid (DIOA) were quantitatively and statistically examined by investigating changes in movement of the cells. Measurement was achieved using subtle variations in dielectrophoresis (DEP) properties of the cells, which were attributed to activation or deactivation of K(+)/Cl(-) cotransporter channels on the cell membrane by the small-molecule drugs, in a microfluidic device. On the basis of quantitative analysis data, we also provide the first report of the shift of the complex permittivity of a cell induced by the small-molecule drugs. In addition, we demonstrate interesting quantifiable parameters including the drug effectiveness coefficient, antagonistic interaction coefficient, kinetic rate, and full width at half-maximum, which corresponded to changes in biological properties of B16F10 cells over time when NEM and DIOA were introduced alone or in combination. Those demonstrated parameters represent very useful tools for evaluating the effect of small-molecule drugs on the biological properties of cells.

Fabrication of high-quality single-crystal Cu thin films using radio-frequency sputtering.

Copper (Cu) thin films have been widely used as electrodes and interconnection wires in integrated electronic circuits, and more recently as substrates for the synthesis of graphene. However, the ultra-high vacuum processes required for high-quality Cu film fabrication, such as molecular beam epitaxy (MBE), restricts mass production with low cost. In this work, we demonstrated high-quality Cu thin films using a single-crystal Cu target and radio-frequency (RF) sputtering technique; the resulting film quality was comparable to that produced using MBE, even under unfavorable conditions for pure Cu film growth. The Cu thin film was epitaxially grown on an Al2O3 (sapphire) (0001) substrate, and had high crystalline orientation along the (111) direction. Despite the 10(-3) Pa vacuum conditions, the resulting thin film was oxygen free due to the high chemical stability of the sputtered specimen from a single-crystal target; moreover, the deposited film had >5× higher adhesion force than that produced using a polycrystalline target. This fabrication method enabled Cu films to be obtained using a simple, manufacturing-friendly process on a large-area substrate, making our findings relevant for industrial applications.

Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney failure.

BACKGROUND AND OBJECTIVES: In ANCA-associated GN, severe renal dysfunction portends a poor prognosis for renal recovery and patient survival. This study evaluated the prognostic factors affecting renal and patient outcomes in patients presenting with severe kidney failure to guide immunosuppressive therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study retrospectively evaluated clinical and histopathologic characteristics of 155 patients who underwent biopsy between October 1985 and February 2011 (median eGFR at presentation, 7.1 ml/min per 1.73 m(2); 87% required hemodialysis), all treated with immunosuppressive medications. Three outcomes of interest were measured: patient survival, renal survival, and treatment response (defined as dialysis-free survival without active vasculitis by 4 months after biopsy). Competing risk, Cox, and logistic regression analyses were conducted for each outcome measure. RESULTS: Within 4 months after biopsy, treatment response was attained in 51% of patients, 35% remained on dialysis, and 14% died. In a competing risk analysis, estimated cumulative incidence rates of ESRD and disease-related mortality were 26% and 17% at 1 year and 32% and 28% at 5 years, respectively. Cyclophosphamide therapy and treatment response by 4 months were independently associated with patient and renal survival, adjusting for the percentage of normal glomeruli, histopathologic chronicity index score, and baseline clinical characteristics. Only 5% of patients still dialysis dependent at 4 months subsequently recovered renal function. Low chronicity index score (odds ratio [OR], 1.16; 95% confidence interval [95% CI], 1.04 to 1.30, per unit decrease) and baseline eGFR>10 ml/min per 1.73 m(2) (OR, 2.77; 95% CI, 1.09 to 7.01) were significantly associated with treatment response by 4 months. Among cyclophosphamide-treated patients, the likelihood of treatment response was >14% even with highest chronicity index score and eGFR<10 ml/min per 1.73 m(2). CONCLUSIONS: Although low baseline renal function and severe renal scarring are associated with lower treatment response rate, no "futility" threshold could be identified. Conversely, continued immunosuppressive therapy beyond 4 months is unlikely to benefit patients who remain dialysis dependent.

Predicting objective function weights from patient anatomy in prostate IMRT treatment planning.

PURPOSE: Intensity-modulated radiation therapy (IMRT) treatment planning typically combines multiple criteria into a single objective function by taking a weighted sum. The authors propose a statistical model that predicts objective function weights from patient anatomy for prostate IMRT treatment planning. This study provides a proof of concept for geometry-driven weight determination. METHODS: A previously developed inverse optimization method (IOM) was used to generate optimal objective function weights for 24 patients using their historical treatment plans (i.e., dose distributions). These IOM weights were around 1% for each of the femoral heads, while bladder and rectum weights varied greatly between patients. A regression model was developed to predict a patient's rectum weight using the ratio of the overlap volume of the rectum and bladder with the planning target volume at a 1 cm expansion as the independent variable. The femoral head weights were fixed to 1% each and the bladder weight was calculated as one minus the rectum and femoral head weights. The model was validated using leave-one-out cross validation. Objective values and dose distributions generated through inverse planning using the predicted weights were compared to those generated using the original IOM weights, as well as an average of the IOM weights across all patients. RESULTS: The IOM weight vectors were on average six times closer to the predicted weight vectors than to the average weight vector, using l2 distance. Likewise, the bladder and rectum objective values achieved by the predicted weights were more similar to the objective values achieved by the IOM weights. The difference in objective value performance between the predicted and average weights was statistically significant according to a one-sided sign test. For all patients, the difference in rectum V54.3 Gy, rectum V70.0 Gy, bladder V54.3 Gy, and bladder V70.0 Gy values between the dose distributions generated by the predicted weights and IOM weights was less than 5 percentage points. Similarly, the difference in femoral head V54.3 Gy values between the two dose distributions was less than 5 percentage points for all but one patient. CONCLUSIONS: This study demonstrates a proof of concept that patient anatomy can be used to predict appropriate objective function weights for treatment planning. In the long term, such geometry-driven weights may serve as a starting point for iterative treatment plan design or may provide information about the most clinically relevant region of the Pareto surface to explore.

Venous thromboembolism in patients with membranous nephropathy.

BACKGROUND AND OBJECTIVES: The aims of this study were to determine the frequency of venous thromboembolic events in a large cohort of patients with idiopathic membranous nephropathy and to identify predisposing risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied patients with biopsy-proven membranous nephropathy from the Glomerular Disease Collaborative Network (n=412) and the Toronto Glomerulonephritis Registry (n=486) inception cohorts. The cohorts were pooled after establishing similar baseline characteristics (total n=898). Clinically apparent and radiologically confirmed venous thromboembolic events were identified. Potential risk factors were evaluated using multivariable logistic regression models. RESULTS: Sixty-five (7.2%) subjects had at least one venous thromboembolic event, and this rate did not differ significantly between registries. Most venous thromboembolic events occurred within 2 years of first clinical assessment (median time to VTE = 3.8 months). After adjusting for age, sex, proteinuria, and immunosuppressive therapy, hypoalbuminemia at diagnosis was the only independent predictor of a venous thromboembolic event. Each 1.0 g/dl reduction in serum albumin was associated with a 2.13-fold increased risk of VTE. An albumin level <2.8 g/dl was the threshold below which risk for a venous thromboembolic event was greatest. CONCLUSIONS: We conclude that clinically apparent venous thromboembolic events occur in about 7% of patients with membranous nephropathy. Hypoalbuminemia, particularly <2.8 g/dl, is the most significant independent predictor of venous thrombotic risk.

Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study.

BACKGROUND/AIMS: Depending on the specific definition, acute kidney injury (AKI) occurs in 7-40% of patients undergoing cardiac surgery. Even small changes in serum creatinine (SCr) levels are associated with increased mortality after cardiac surgery. However, there are no current methods for preventing AKI after cardiac surgery. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in various experimental models. In this pilot trial, we evaluated the effectiveness of EPO in the prevention of AKI after coronary artery bypass grafting (CABG). METHODS: 71 patients scheduled for elective CABG randomly received either 300 U/kg of EPO or saline intravenously before surgery. AKI was defined as a 50% increase in SCr levels over baseline within the first 5 postoperative days. Estimated glomerular filtration rate (eGFR) was calculated from the Cockcroft-Gault equation. RESULTS: Of 71 patients, 13 developed postoperative AKI: 3 of the 36 patients in the EPO group (8%) and 10 of the 35 patients in the placebo group (29%; p = 0.035). The increase in postoperative SCr concentration and the decline in postoperative eGFR were significantly lower in the EPO group than in the placebo group. CONCLUSIONS: In our small, pilot trial, prophylactic administration of EPO prevents AKI and improves postoperative renal function. These data are preliminary and require confirmation in a larger clinical trial.

Treatment of Cr(VI) and phenol by illuminated TiO2.

Industrial wastewater from organic chemical manufacturing and metal plating industries may contain significant amounts of refractory organic matter and heavy metals. Heavy metals such as Cr(VI) and refractory organic matter like phenol were simultaneously removed by reduction and mineralization, respectively, during photocatalytic process. Therefore, this study was carried out to evaluate the effects of phenol on the removal of Cr(VI) in several environmental conditions. Cr(VI) and phenol were more effectively eliminated in UV/TiO2 condition than either by UV or TiO2-alone. The removal efficiencies of Cr(VI) increased as the pH of the TiO2 slurry decreased, the concentration of phenol increased up to 10 mg L(-1), and nitrogen gas was used. Otherwise, the removal efficiencies of phenol were higher at O2-purged system and neutral pH. Without regard to purging gases, complete Cr(VI) removal was observed at pH 4 after 80 min while 90% phenol destruction and 60% mineralization were found after 120 min. It wasfound that application of photocatalytic reaction by using illuminated TiO2 to treat wastewater containing both Cr(VI) and phenol was possible.

Stoichiometry and structural effect of the cyclic nucleotide binding to cyclic AMP receptor protein.

Cyclic AMP receptor protein (CRP) is a homodimeric protein, which is activated by cAMP binding to function as a transcriptional regulator of many genes in prokaryotes. Until now, the actual number of cAMP molecules that can be bound by CRP in solution has been ambiguous. In this work, we performed a nuclear magnetic resonance study on CRP to investigate the stoichiometry of cyclic nucleotide binding to CRP. A series of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the protein in the absence and in the presence of cAMP or cGMP were analyzed. The addition of cAMP to CRP induced a biphasic spectral change up to 4 equivalents, whereas the cGMP addition made a monophasic change up to 2 equivalents. Altogether, the results not only established for the first time that CRP possesses two cyclic AMP-binding sites in each monomer, even in a solution without DNA, but also suggest that the syn-cAMP binding sites of the CRP dimer can be formed by an allosteric conformational change of the protein upon the binding of two anti-cAMPs at the N-terminal domain. In addition, a residue-specific inspection of the spectral changes provides some new structural information about the cAMP-induced allosteric activation of CRP.