Cost-effectiveness analysis of interventional liver-directed therapies for downstaging of HCC before liver transplant.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are the 2 most used modalities for patients with HCC while awaiting liver transplant. The purpose of this study is to perform a cost-effectiveness analysis comparing TACE and TARE for downstaging (DS) patients with HCC. A cost-effectiveness analysis was performed comparing TACE and TARE in DS HCC over a 5-year time horizon from a payer's perspective. The clinical course, including those who achieved successful DS leading to liver transplant and those who failed DS with possible disease progression, was obtained from the United Network for Organ Sharing. Costs and effectiveness were measured in US dollars and quality-adjusted life years (QALYs). Probabilistic and deterministic sensitivity analyses were performed. TARE achieved a higher effectiveness of 2.51 QALY (TACE: 2.29 QALY) at a higher cost of $172,162 (TACE: $159,706), with the incremental cost-effectiveness ratio of $55,964/QALY, making TARE the more cost-effective strategy. The difference in outcome was equivalent to 104 days (nearly 3.5 months) in compensated cirrhosis state. Probabilistic sensitivity analyses showed that TARE was more cost-effective in 91.69% of 10,000 Monte Carlo simulations. TARE was more effective if greater than 48.2% of patients who received TACE or TARE were successfully downstaged (base case: 74.6% from the pooled analysis of multiple published cohorts). TARE became more cost-effective when the cost of TACE exceeded $4,831 (base case: $12,722) or when the cost of TARE was lower than $43,542 (base case: $30,609). Subgroup analyses identified TARE to be the more cost-effective strategy if the TARE cohort required 1 fewer locoregional therapy than the TACE cohort. TARE is the more cost-effective DS strategy for patients with HCC exceeding Milan criteria compared to TACE.

Comparison of Minimally Invasive Procedures for Benign Prostatic Hyperplasia: A Cost-effectiveness Analysis.

Background Benign prostatic hyperplasia (BPH) is a disease that affects millions of U.S. men and is costly to treat. Purpose To compare the cost-effectiveness of four minimally invasive therapies (MITs) and medical management for the treatment of BPH. Materials and Methods A cost-effectiveness analysis from a payer's perspective with Markov modeling was performed, comparing prostatic artery embolization (PAE), prostatic urethral lift, aquablation, water vapor thermal therapy, and medical management for BPH spanning a time horizon of 5 years. The model incorporated the probability of procedural complications and recurrent symptoms necessitating retreatment, which were extracted from published studies with long-term follow-up. Costs were based on Medicare reimbursements using CPT codes for ambulatory surgery centers. Outcomes were measured using the quality-adjusted life year (QALY), incorporating both life quality and expectancy. Statistical analyses included a base case calculation (using the most probable value of each parameter) and probabilistic and deterministic sensitivity analyses. Results In the base case calculation, outcomes for the strategies were comparable, with a difference of 0.030 QALY (11 days of life in perfect health) between the most (PAE) and least (medical management) effective strategies. PAE was the most cost-effective strategy relative to medical management, with an incremental cost-effectiveness ratio of $64 842 per QALY. Probabilistic sensitivity analysis showed PAE was more cost-effective compared with prostatic urethral lift, aquablation, water vapor therapy, and medical management in pairwise comparisons. In sensitivity analysis of retreatment risk, PAE remained the most cost-effective strategy until its repeat treatment rates exceeded 2.30% per 6 months, at which point water vapor therapy became the optimal choice. PAE was the most cost-effective procedure when its procedural cost was lower than $4755. Aquablation and prostatic urethral lift became more cost-effective when their procedural costs were lower than $3015 and $1097, respectively. Conclusion This modeling-based study showed that PAE appears to be a cost-effective modality among medical management and MITs for patients with BPH, with comparable outcomes to prostatic urethral lift, water vapor therapy, and aquablation at a lower expected cost. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Gemmete in this issue.

Cost-Effectiveness Analysis of Interventional Liver-Directed Therapies for a Single, Small Hepatocellular Carcinoma in Liver Transplant Candidates.

PURPOSE: To assess the cost effectiveness of 3 main locoregional therapies (LRTs) (transarterial chemoembolization [TACE], transarterial radioembolization [TARE], and percutaneous ablation) as bridging therapy. MATERIALS AND METHODS: A cost-effectiveness analysis was performed comparing the 3 LRTs for patients with a single hepatocellular carcinoma (HCC) with a diameter of 3 cm or less over a 5-year time horizon from a payer's perspective. The clinical courses, including transplantation, decompensation resulting in delisting, and the need for a second LRT, were based on data from the United Network for Organ Sharing (2016-2019). Costs and effectiveness were measured in U.S. dollars and quality-adjusted life-years, respectively. Probabilistic and deterministic sensitivity analyses were performed. RESULTS: A total of 2,594, 1,576, and 903 patients underwent TACE, ablation, and TARE, respectively. Ablation was the dominant strategy, with the lowest expected cost and highest effectiveness. The probabilistic sensitivity analysis demonstrated that ablation was the most cost-effective strategy in 93.9% of simulations. A subgroup analysis was performed for different wait times, with ablation remaining the most cost-effective strategy. The sensitivity analysis showed that ablation was most effective if the risk of waitlist dropout was less than 2.00% and the rate of transplantation was more than 15.1% quarterly. TARE was most effective if the risk of dropout was less than 1.19% and the rate of transplantation was more than 24.0%. TACE was most effective if the risk of dropout was less than 1.01% and the rate of transplantation was more than 45.7%. Ablation remained the most cost-effective modality until its procedural cost was more than $34,843. CONCLUSIONS: Ablation is the most cost-effective bridging strategy for patients with a single, small (≤3 cm) HCC prior to liver transplantation. The conclusion remained robust in multiple sensitivity analyses.

Socioeconomic and Survival Analysis of Radioembolization in Patients with Intrahepatic Cholangiocarcinoma: A Propensity Score-Adjusted Study.

PURPOSE: To determine whether transarterial radioembolization (TARE) is associated with longer survival of patients with intrahepatic cholangiocarcinoma (ICC) and whether access to TARE is influenced by socioeconomic factors. MATERIALS AND METHODS: Retrospective review of patients with ICC in the National Cancer Database from 2004 to 2018 was performed with Cox regression analysis to identify predictors of survival. Overall survival (OS) was estimated using the Kaplan-Meier method. Socioeconomic factors were compared between 2 groups using the Wilcoxon rank-sum test and χ2 test. Propensity score-matched cohorts were created between patients with ICC who did and did not undergo TARE. RESULTS: The number of patients receiving TARE for ICC increased over time from 1 in 2004 to 210 in 2018. Patients in the TARE group were more likely to be White (87.9% vs 84.3%; P = .012) and less likely to be Hispanic/Latino (7.7% vs 11.0%; P = .009). Fewer patients who underwent TARE were uninsured (0.9% vs 2.8%; P = .012). Older age, male sex, non-White race, higher tumor grade size, and stage, earlier year of diagnosis, lack of treatment with surgery or systemic therapy, and presence of lymphatic or vascular invasion exhibited significant associations with decreased survival (P < .05 for all). Patients who underwent TARE had longer survival in both unadjusted and adjusted cohorts, with an OS of 17.5 months (vs 7.2 months in the non-TARE group) after propensity matching. CONCLUSIONS: Patients with ICC who had undergone TARE experienced significantly longer survival than that experienced by those who had not after adjusting for measurable confounders. Significant socioeconomic disparities in access to TARE remain.

cyc-DEP: Cyclic immunofluorescence profiling of particles collected using dielectrophoresis.

Cancer is a highly heterogenous disease that requires precise detection tools and active surveillance methods. Liquid biopsy assays provide an agnostic way to follow the complex trajectory of cancer, providing better patient stratification tools for optimized treatment. Here, we present the development of a low-volume liquid biopsy assay called cyc-DEP (cyclic immunofluorescent imaging on dielectrophoretic chip) to profile biomarkers collected on a dielectrophoretic microfluidic chip platform. To enable on-chip cyclic imaging, we optimized a fluorophore quenching method and sequential rounds of on-chip staining with fluorescently conjugated primary antibodies. cyc-DEP allows for the quantification of a multiplex array of proteins using 25 µl of a patient plasma sample. We utilized nanoparticles from a prostate adenocarcinoma (LNCaP) cell line and a panel of six target proteins to develop our proof-of-concept technique. We then used cyc-DEP to quantify blood plasma levels of target proteins from healthy individuals, low-grade and high-grade prostate cancer patients (n = 3 each) in order to demonstrate that our platform is suitable for liquid biopsy analysis in its present form. To ensure accurate quantification of signal intensities and comparisons between different samples, we incorporated a signal intensity normalization method (fluorescent beads) and a custom signal intensity quantification algorithm that account for the distribution of signal across hundreds of collection regions on each chip. Our technique enabled a threefold improvement in multiplicity for detecting proteins associated with fluid samples, opening doors for early detection, and active surveillance through quantification of a multiplex array of biomarkers from low-volume liquid biopsies.

Cost-effectiveness of tunneled peritoneal catheters versus repeat paracenteses for recurrent ascites in gynecologic malignancies.

OBJECTIVE: To compare the cost-effectiveness of tunneled peritoneal catheter (TPC) versus repeated large-volume paracentesis (LVP) for patients with recurrent ascites secondary to gynecological malignancy. METHODS: A retrospective cohort study was performed at a single institution from 2016 through 2019 of patients with recurrent ascites from gynecologic malignancies that underwent either TPC or LVP. Data on procedural complications and hospital admissions were extracted. A cost-effectiveness analysis with Markov modeling was performed comparing TPC and LVP. Statistical analyses include base case calculation, Monte Carlo simulations and deterministic sensitivity analyses. RESULTS: There were no significant differences between the cohorts in the average number of hospital days (p = 0.21) or emergency department visits (p = 0.69) related to ascites. Palliative care was more often involved in the care of patients who had a TPC. The base case calculation showed TPC to be the more cost-effective strategy with a slightly lower health benefit (0.22980 versus 0.22982 QALY) and lower cost ($3043 versus $3868) relative to LVP (ICER of LVP compared to TPC: $44,863,103/QALY). Probabilistic sensitivity analysis showed TPC was the more cost-effective strategy in 8028/10,000 simulations. Deterministic sensitivity analysis showed TPC to be more cost-effective if its complication risk was >0.81% per 22 days or its procedural cost of TPC insertion was >$1997. When varying the cost of complications, TPC was more cost-effective if the cost of its complication was less than $49,202. CONCLUSIONS: TPC is the more cost-effective strategy when compared to LVP in patients with recurrent ascites from gynecological malignancy.

Prostatic Artery Embolization Versus Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia: A Cost-Effectiveness Analysis.

PURPOSE: To compare the cost effectiveness of prostatic artery embolization (PAE) with that of transurethral resection of the prostate (TURP) for the treatment of medically refractory benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A cost-effectiveness analysis with Markov modeling was performed, comparing the clinical course after PAE with that after TURP for 3 years. Probabilities were obtained from the available literature, and costs were based on Medicare reimbursements and published cost analyses. Outcomes were measured using quality-adjusted life-year (QALY). Statistical analyses included base case calculation, probabilistic sensitivity analysis, and deterministic sensitivity analysis to assess the robustness of the conclusion under different clinical scenarios. RESULTS: Base case calculation showed comparable outcomes (PAE, 2.845 QALY; TURP, 2.854 QALY), with a cost difference of $3,104 (PAE, $2,934; TURP, $6,038). The incremental cost-effectiveness ratio was $360,249/QALY. PAE was dominant in 23.2% and more cost effective in 48.4% of the probabilistic sensitivity analysis simulations. PAE was better if its recurrence risk was <20.4% per year and even when the TURP recurrence risk was assumed to be 0%. TURP would be more cost effective when its procedural cost was <$3,367 or the PAE procedural cost >$4,409. PAE remained cost effective when varying the risks and costs of the minor and major short-term or long-term adverse events of both procedures. TURP would be the better strategy if the utility of BPH recurrence was <0.85 QALY. CONCLUSIONS: PAE is a cost-effective strategy to treat medically refractory BPH, resulting in comparable health benefits at a lower cost than that of TURP even when accounting for extreme alterations in adverse events, costs, and recurrence rates.

Geniculate Artery Embolization: Role in Knee Hemarthrosis and Osteoarthritis.

Roughly 37% of Americans 60 years of age and older experience chronic pain due to osteoarthritis (OA) of the knee. After conservative treatment (pharmacologic, physical therapy, and joint injections) fails, patients often require total knee arthroplasty to alleviate pain and regain knee function. Given the high economic burden of surgery paired with its invasive nature, many patients with this degenerative joint disease seek alternative treatment. Moreover, many patients with severe knee OA who also have comorbidities that preclude surgery-most often morbid obesity-are left without options. Geniculate artery embolization (GAE) is a minimally invasive intra-arterial intervention that was originally developed for the treatment of knee hemarthrosis that has recently been adapted for symptomatic knee OA. Through selective embolization of geniculate branches corresponding to the site of knee pain, GAE inhibits the neovascularity that contributes to the catabolic and inflammatory drive of OA. Preliminary trials over the past decade have demonstrated promising clinical results, including decreased pain and improved function and quality of life after treatment. Given such success, GAE provides another minimally invasive treatment option for knee OA to patients who feel reluctant to undergo or are ineligible for surgery. The authors review the radiographic manifestations and current standard of treatment of OA and hemarthrosis of the knee. Procedural technique, embolic selection, and clinical evidence for GAE in the treatment of OA and hemarthrosis of the knee are also explored. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2021.

A longitudinal study of naloxone opioid overdose awareness and reversal training for first-year medical students: specific elements require reinforcement.

BACKGROUND: The opioid epidemic is a progressively worsening public health crisis that continues to impact healthcare system strategies such as overdose reversal and destigmatization. Even among healthcare professionals, there remains a lack of confidence in naloxone administration and a prevalence of stigma. While training can play a major impact in reducing these shortcomings, the long-term effectiveness has yet to be characterized in training healthcare professionals. This study examined the long-term retention of opioid overdose awareness and reversal training (OOART) by evaluating performance at two-time intervals, immediately post-training and at a 3-month follow-up. METHODS: Voluntary training was offered to first-year (M1) medical students at the Drexel University College of Medicine in 2021. At this training, 118 students completed training, 95 completed the post-training survey, and 42 completed the 3-month follow-up. RESULTS: Opioid reversal knowledge questions assessed significantly increased scores post-training and at the 3-month follow-up. In three of the attitude questions, scores were improved at both follow-up timepoints. In addition, three attitude questions indicating a participant's confidence to respond to an opioid overdose situation increased directly after the training, but regressed at the 3-month follow-up. The remaining questions did not show any statistical difference across the survey intervals. CONCLUSIONS: This study establishes that while OOART provides participants with the knowledge of how to respond to an opioid overdose, the retention of this knowledge at a 3-month interval is reduced. The results were mixed for longitudinal assessment of participant's attitudes toward people with opioid use disorder. Some positive increases in attitudes were retained at the 3-month interval, while others trended back toward pre-training levels. These results support the effectiveness of the training but also provide evidence that OOART must be reinforced often.

Dielectrophoresis: Developments and applications from 2010 to 2020.

The 20th century has seen tremendous innovation of dielectrophoresis (DEP) technologies, with applications being developed in areas ranging from industrial processing to micro- and nanoscale biotechnology. From 2010 to present day, there have been 981 publications about DEP. Of over 2600 DEP patents held by the United States Patent and Trademark Office, 106 were filed in 2019 alone. This review focuses on DEP-based technologies and application developments between 2010 and 2020, with an aim to highlight the progress and to identify potential areas for future research. A major trend over the last 10 years has been the use of DEP techniques for biological and clinical applications. It has been used in various forms on a diverse array of biologically derived molecules and particles to manipulate and study them including proteins, exosomes, bacteria, yeast, stem cells, cancer cells, and blood cells. DEP has also been used to manipulate nano- and micron-sized particles in order to fabricate different structures. The next 10 years are likely to see the increase in DEP-related patent applications begin to result in a greater level of technology commercialization. Also during this time, innovations in DEP technology will likely be leveraged to continue the existing trend to further biological and medical-focused applications as well as applications in microfabrication. As a tool leveraged by engineering and imaginative scientific design, DEP offers unique capabilities to manipulate small particles in precise ways that can help solve problems and enable scientific inquiry that cannot be addressed using conventional methods.

Electrochemical attack and corrosion of platinum electrodes in dielectrophoretic diagnostic devices.

Though the advances in microelectronic device fabrication have realized new capabilities in integrated analytical and diagnostic platforms, there are still notable limitations in point-of-care sample preparation. AC electrokinetic devices, especially those leveraging dielectrophoresis (DEP), have shown potential to solve these limitations and allow for sample-to-answer in a single point-of-care device. However, when working directly with whole blood or other high conductance (~ 1 S/m) biological fluids, the aggressive electrochemical conditions created by the electrode can fundamentally limit the device operation. In this study, platinum wire-based electrode devices spanning circular polytetrafluorethylene (PTFE) wells and a planar microarray device with sputtered platinum electrodes were tested in plasma and PBS buffers of differing concentration across a wide range of frequencies and electric field intensities (AC voltages) to determine their respective safe regions of operation and to gain an understanding about the failure mechanisms of this class of device. At frequencies of 10 kHz and below, the upper bound of operation is the degradation of electrodes due to electrochemical attack by chlorine overcoming the native platinum oxide passivation. At higher frequencies, 100 kHz and above, the dielectric loss and subsequent heating of the buffer will boil before the electrodes suffer observable damage, due to the slow irreversible reaction kinetics. Effective dielectrophoretic capture of small biological particles at these frequencies is limited, and heat/oxidative denaturation of target material are a major concern. A new class of smaller devices, ones capable of high throughput at voltages low enough to maintain the integrity of the platinum passivation layer, is needed to mitigate these fundamental limitations.

Arthroscopic shoulder stabilization in the young athlete: return to sport and revision stabilization rates.

BACKGROUND: Shoulder instability in young athletes is a complex problem with higher recurrence, higher reoperation, and lower return to sport (RTS) rates after arthroscopic shoulder stabilization compared with adults. METHODS: This is a prospective case series of young athletes with anterior shoulder instability after arthroscopic stabilization surgery. Primary outcomes were RTS and revision surgery, minimum follow-up was 24 months. Exclusion criteria were more than 3 preoperative episodes of instability, significant bone loss, or primary posterior instability. Demographic data, recurrent instability, revision surgery, sports pre- and postsurgery, patient satisfaction, level of RTS, time to RTS, and Single Assessment Numeric Evaluation (SANE) scores were analyzed. RESULTS: Sixty-seven athletes met inclusion criteria, 19 females and 48 males, with a mean age of 17.5 years (range, 13-21 years). Fifty-nine (88%) athletes returned to sport at an average of 7.1 months (standard deviation, ±1.8); 50 (75%) returned to the same level or higher. Football and lacrosse were the most common sports. Four of 67 athletes (6%), all male, underwent revision stabilization at 11-36 months for recurrent instability. The overall mean SANE score was 88. CONCLUSION: This study demonstrates that when the high-risk athlete, 21 years old or younger, is appropriately selected for arthroscopic shoulder stabilization by excluding those with 3 or more preoperative shoulder instability episodes and those with off-track and engaging instability patterns, excellent outcomes can be achieved with low revision surgery rates, high RTS rates, and high patient satisfaction.

Elevated Resting and Postprandial Digestive Proteolytic Activity in Peripheral Blood of Individuals With Type-2 Diabetes Mellitus, With Uncontrolled Cleavage of Insulin Receptors.

Objective: To examine resting and postprandial peripheral protease activity in healthy controls and individuals with type 2 diabetes mellitus (T2DM) and pre-T2DM. Methods: Individuals with T2DM or pre-T2DM and healthy controls (mean age 55.8 years) were studied before and for a span of 300 minutes following a single high-calorie McDonald's breakfast. Metalloproteases-2/-9 (MMP-2/-9), elastase, and trypsin activities were assessed in whole blood before and following the meal using a novel high-precision electrophoretic platform. Also assessed were circulating levels of inflammatory biomarkers and insulin receptor density on peripheral blood mononuclear cells (PBMCs) in relationship to protease activity. Results: Premeal MMP-2/-9 and elastase activity levels in T2DM and in pre-T2DM participants were significantly elevated as compared to controls. The T2DM group showed a significant increase in elastase activity 15 minutes after the meal; elastase activity continued to increase to the 30-minute time point (p < 0.01). In control participants, MMP-2/-9, elastase, and trypsin were significantly increased at 15 minutes after the meal (p < 0.05) and returned to premeal values within a period of approximately 30 to 60 minutes post meal. PBMCs incubated for 1 hour with plasma from T2DM and pre-T2DM participants had significantly lower levels of insulin receptor density compared to those incubated with plasma from control participants (p < 0.001). Conclusions: The results of this study suggest that individuals with T2DM and pre-T2DM have higher resting systemic protease activity than nonsymptomatic controls. A single high-calorie/high-carbohydrate meal results in further elevations of protease activity in the systemic circulation of T2DM and pre-T2DM, as well as in healthy controls. The protease activity in turn can lead to a downregulation of insulin receptor density, potentially supporting a state of insulin resistance.

Left ventricular perforation with catheter decompression.

Thoracostomy tube placement is one of the more common procedures performed in the Emergency Department, most commonly for treatment of pneumothorax or hemothorax but occasionally for drainage of empyema or pleural effusion. Thoracostomy may be a life-saving procedure with a wide range of complication rates reported, ranging from 19.4-37%, most commonly extrathoracic placement. Most recent meta-analyses showed a relatively stable complication rate of 19% over the past three decades with the vast majority being benign in nature. We present a case with the rare complication of thoracostomy in which of a small-caliber thoracostomy tube was placed in the left ventricle. Although thoracotomy was performed to remove the catheter, the patient remained virtually asymptomatic and had an uneventful course.

Concomitant Infection With Epstein-Barr Virus and Cytomegalovirus Infection Leading to Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is well recognized as a complication of hepatic cirrhosis and is likely to be suspected in patients with hypercoagulable syndromes, however, it is rarely recognized as a possibility in otherwise healthy patients with Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection. We report a case of a healthy 27-year-old man with fever and weight loss who was found to have PVT in the setting of acute EBV and CMV infection. CASE REPORT: A 27-year-old man with no known medical history presented to the emergency department (ED) for fever for 18 days. Patient reported daily high fevers associated with chills, night sweats, generalized myalgia, nausea with appetite loss, and unquantified weight loss. Vital signs showed temperature of 100.5°F. Patient reported discomfort upon palpation of abdomen on physical examination. There was no lymphadenopathy, cardiac murmur, rash, or jaundice. Laboratory tests revealed titers diagnostic of acute EBV and CMV infection with elevated liver function tests and leukocytosis with lymphocyte predominance (white blood cell count 15,400/µL; 43% atypical lymphocytes). Computed tomography of the abdomen/pelvis with i.v. contrast showed a filling defect in the anterior portal vein. The patient was admitted with the ED diagnosis of PVT secondary to viral infection and was initiated on anticoagulation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although rarely considered, CMV has been associated with PVT in up to 6% of cases, and EBV infection has been implicated as well. Emergency physicians should be aware of this potentially serious complication of these common viral infections and consider imaging modalities to rule out thrombosis, if appropriate.

Intracardiac Venous Stent Migration: Emergency Department Presentation of a Catastrophic Complication.

BACKGROUND: Venous stents are commonly placed to ensure patency in patients with chronic peripheral venous insufficiency. Although serious complications are uncommon, peripheral venous stent placement can have some potentially life-threatening complications. One of the most feared, and certainly the most dramatic, complication is stent migration. CASE REPORT: We report on a 55-year-old woman with transvenous migration of an infrarenal inferior vena cava stent into the right atrium and through the intra-atrial septum. The patient expired in the emergency department (ED). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: There are several potentially life-threatening post-surgical complications after an endovascular procedure, some of which occur shortly after the patient is discharged from the recovery unit. Frequently, these patients present to the ED for initial evaluation. Although details of the procedure performed and the surgical intervention might not be available immediately, emergency physicians should consider stent migration when a patient presents in extremis shortly after an endovascular procedure.

Thrombin generation assay in untreated whole human blood.

Present coagulation assays fail to detect mild coagulation disorders, while thrombin-generation (TG) assays solve this problem. However, most of them only work with threated blood samples, which makes them labor intensive, time consuming, unreliable, and expensive. We have developed a TG electrophoretic assay that uses a thrombin specific charge-changing fluorescent peptide substrate, electrophoretic separation, and requires a drop of blood. The limit of detection of the assay was 1.97 nM in phosphate buffer saline and 6.82 nM in citrated whole blood. The assay was used to determine the TG in whole blood from healthy volunteers (n = 6, one aspirin user), over 30 min, after the blood was drawn; the TG increased from a baseline level of 2 × 10(6) RFU to 1.2 × 10(13) RFU. The lag time between the blood draw and initial burst of TG was 6 min for the volunteers (n = 5) and 15 min for the aspirin user. Specificity of the assay was evaluated by reacting our substrate with the heparinized blood samples and other proteases. The TG electrophoretic assay was designed and tested in the whole human blood, requiring no sample preparation, 5 µL of blood, 45 min, and it detected differences in coagulation patterns between a volunteer taking aspirin and non-aspirin users.

Enhanced fluorescent resonant energy transfer of DNA conjugates complexed with surfactants and divalent metal ions.

Dimerization and resultant quenching of donor and acceptor dyes conjugated on DNA causes loss of fluorescent resonant energy transfer (FRET) efficiency. However, when complexed with surfactants and divalent metal ions, sheathing effects insulate and shield the DNA structures, reducing dimerization and quenching which leads to significant enhancement of FRET efficiency.

An Aqueous Single Reactor Arc Discharge Process for the Synthesis of Graphene Nanospheres.

Using an aqueous single reactor arc discharge process with oil-in-water emulsions allows production of 2D multilayered graphenes (MLGs and 3D graphene-based crumpled/sphere-like particles with low levels of defects). The confinement forces to create 3D particles from 2D MLGs are estimated to be 2.5 µN for crumpled particles and 70 µN for spherical hollow particles.