Industry relationships with interventional radiologists: Who are the high payment physicians?

PURPOSE: To identify characteristics of interventional radiologists receiving more than $100,000 in general industry payments over a 5-year period (2017-2021). METHODS: The Open Payments database was queried to identify interventional radiologists who received more than $100,000 in consulting fees, speaker fees, education, and/or gifts over a 5-year period from 2017 to 2021. The national provider identifier registry, Scopus, and a web-based search were used to identify physician characteristics, such as demographics, research profile, leadership positions, and social media presence. RESULTS: From 2017-2021, 125 interventional radiologists received cumulative payments greater than $100,000 in consulting fees, speaker fees, education, and gifts. For this subset of physicians, the median (IQR) cumulative payment value was $214,380 ($141,812 - $383,740), and the total payment value was $40 million. While the highest-paid subset of physicians represented only 3 % (125/4272) of all US interventional radiologists paid by industry, the total payment value represented 66 % ($40,039,610.08/$60,859,025) of the total payment value among all interventional radiologists. 47 % (59/125) had faculty appointments and 30 % (37/125) had hospital leadership positions. 22 % (27/125) were clinical practice guideline authors, while 18 % (23/125) served on journal editorial boards and 12 % (15/125) had positions in specialty association leadership. Castle Connolly recognized 26 % (32/125) as top doctors. Among the 96 % (120/125) with published research in the past 5 years, the median (IQR) H-index was 17 (7-31). 38 % (48/125) had a presence on Twitter with a median (IQR) Kardashian index of 2.03 (0.48-6.16). CONCLUSION: A small subset of interventional radiologists receive large payments from drug and medical device companies. These physicians are leaders in their field with influence in hospitals, research, associations, and social media. Further work is needed to understand how the concentration of these payments affects decisions in clinical practice and policy.

Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts.

INTRODUCTION: The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During this process, collagen fragments or neoepitopes, are released into the circulation. The significance of these circulating collagen neoepitopes in sarcoidosis remains unknown. METHODS: We employed plasma samples from patients with sarcoidosis enrolled in A Case Control Etiologic Study of Sarcoidosis (ACCESS) and Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS), and healthy control patients recruited from the Yale community. Plasma concentrations of type III and VI collagen degradation (C3M and C6M) and formation (PRO-C3 and PRO-C6) were quantified via neoepitope-specific competitive ELISA, and statistical associations were sought with clinical phenotypes. RESULTS: Relative to healthy controls, the plasma of both sarcoidosis cohorts was enriched for C3M and C6M, irrespective of corticosteroid use and disease duration. While circulating collagen neoepitopes were independent of Scadding stage, there was a significant association between multiorgan disease and PRO-C3, PRO-C6 and C3M in the ACCESS cohort; PRO-C3 and C6M displayed this property in GRADS. These findings were unrelated to plasma levels of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10 and IL-13. Moreover, PRO-C3 was associated with dermatological disease in both cohorts. DISCUSSION: In two well-characterised sarcoidosis cohorts, we discovered that the plasma is enriched for neoepitopes of collagen degradation (C3M and C6M). In multiorgan disease, there was an association with circulating neoepitopes of type III formation (PRO-C3), perhaps mediated by dermatological sarcoidosis. Further investigation in this arena has the potential to foster new insights into the pathogenic mechanisms of this complex disease.

Proportion of industry payment value by category in radiology relative to other specialties.

BACKGROUND: Industry payments to physicians are common, but it is unknown how the payments in different categories to radiologists compare to other specialties. OBJECTIVE: The aim of this study is to assess the proportion of industry payments to physicians in radiology in certain categories relative to other specialties. METHODS: The Open Payments Database was analyzed from January 1, 2017 to December 31, 2021 for industry payments to all allopathic & osteopathic physicians, and classified into distinct clinical specialties. Payments to physicians in three categories were calculated in relation to total payments in each specialty during the study period: consulting fees, research, and royalties/ownership (royalty, license, or current or prospective ownership or investment). RESULTS: The total value of industry payments to physicians across all specialties was just under $13 billion over the six-year period from 2017 to 2022. During this period, 51.4 million total payments were made to 791,746 physicians. US physicians in radiology received 452,027 payments for a total value of $357 million (2.8 % of total value). For radiologists, 32.8 % of industry payment value was attributed to royalties/ownership and 9.9 % to research, collectively adding up to 42.7 % of all industry payment. The only specialties with higher payments in these two categories considered reflective of innovation payments were the surgical specialties with higher royalty payments. CONCLUSION: The proportion of industry payments in radiology in categories reflecting innovation (royalty/ownership and research fees) is high and second only to surgical specialties.

Utilising raw psycho-physiological data and functional data analysis for estimating mental workload in human drivers.

Recent studies have focused on accurately estimating mental workload using machine learning algorithms and extracting features from physiological measures. However, feature extraction leads to the loss of valuable information and often results in binary classifications that lack specificity in the identification of optimum mental workload. This study investigates the feasibility of using raw physiological data (EEG, facial EMG, ECG, EDA, pupillometry) combined with Functional Data Analysis (FDA) to estimate the mental workload of human drivers. A driving scenario with five tasks was employed, and subjective ratings were collected. Results demonstrate that the FDA applied nine different combinations of raw physiological signals achieving a maximum 90% accuracy, outperforming extracted features by 73%. This study shows that the mental workload of human drivers can be accurately estimated without utilising burdensome feature extraction. The approach proposed in this study offers promise for mental workload assessment in real-world applications.

This study aimed to estimate the mental workload of human drivers using physiological signals and Functional Data Analysis (FDA). By comparing models using raw data and extracted features, the results show that the FDA with raw data achieved a high accuracy of 90%, outperforming the model with extracted features (73%).

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND AND OBJECTIVE: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. METHODS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. KEY FINDINGS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm.

Salary Equity in Academic Radiology Relative to Other Clinical Specialties.

BACKGROUND: Equity in faculty compensation in U.S. academic radiology physicians relative to other specialties is not well known. OBJECTIVE: The aim of this study is to assess salary equity in U.S. academic radiology physicians at different ranks relative to other clinical specialties. METHODS: The American Association of Medical Colleges (AAMC) Faculty Salary Survey was used to collect information for full-time faculty at U.S. medical schools. Financial compensation data were collected for 2023 for faculty with MD or equivalent degree in medical specialties, stratified by gender and rank. RESULTS: The AAMC Faculty Salary Survey data for 2023 included responses for 97,224 faculty members in clinical specialties, with 5847 faculty members in Radiology departments. In radiology, compared to men (n = 3839), the women faculty members (n = 1763) had a lower median faculty compensation by 6% at the rank of Assistant Professor, 3% for Associate Professors, 4% for Professors and 6% for Section Chief positions. Surgery had the highest difference in median compensation with 21%, 24%, 22% and 19% lower faculty compensation, respectively, for women faculty members at corresponding ranks. Pathology had the lowest percent difference (<1%) in median compensation for all professor ranks. Salary inequity in radiology was lower compared to most other specialties. From assistant to full professors, all other clinical specialties except Pathology and Psychiatry, had a greater salary inequity than Radiology. CONCLUSION: The salary inequity in academic radiology faculty is lower than most other specialties. Further efforts should be made to reduce salary inequities as broader efforts to provide a more diverse, equitable and inclusive environment. SUMMARY STATEMENT: Salary inequity in academic radiology faculty is lower than most other specialties.

Anatomical Features can Affect OCT Measures Used for Clinical Decisions and Clinical Trial Endpoints.

Purpose: To understand the association between anatomical parameters of healthy eyes and optical coherence tomography (OCT) circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. Methods: OCT cpRNFL thickness was obtained from 396 healthy eyes in a commercial reference database (RDB). The temporal quadrant (TQ), superior quadrant (SQ), inferior quadrant (IQ), and global (G) cpRNFL thicknesses were analyzed. The commercial OCT devices code these values based on percentiles (red, <1%; yellow, ≥1% and <5%), after taking age and disc area into consideration. Four anatomical parameters were assessed: fovea-to-disc distance, an estimate of axial length, and the locations of the superior and the inferior peaks of the cpRNFL thickness curve. Pearson correlation values were obtained for the parameters and the thickness measures of each of the four cpRNFL regions, and t-tests were performed between the cpRNFL thicknesses coded as abnormal (red or yellow, <5%) versus normal (≥5%). Results: For each of the four anatomical parameters, the correlation with the thickness of one or more of the TQ, SQ, IQ, and G regions exceeded the correlation with age or disc area. All four parameters were significantly (P < 0.001) associated with the abnormal cpRNFL values. The significant parameters were not the same for the different regions; for example, a parameter could be negatively correlated for the TQ but positively correlated with the SQ or IQ. Conclusions: In addition to age and disc area, which are used for inferences in normative databases, four anatomical parameters are associated with cpRNFL thickness. Translational Relevance: Taking these additional anatomical parameters into consideration should aid diagnostic accuracy.

Diabetes Research Matters: A Three-Round Priority-Setting Survey Consultation with Adults Living with Diabetes and Family Members in Australia.

OBJECTIVE: We aimed to identify the health and quality-of-life research priorities of Australians with diabetes or family members. METHODS: Through an iterative, three-step, online survey process we (1) qualitatively generated research topics (long list) in response to one question "What research is needed to support people with diabetes to live a better life?"; (2) determined the most important research questions (short list); and (3) ranked research questions in order of importance (priorities). We aimed to recruit N = 800 participants, with approximate equal representation of diabetes type and family members. RESULTS: Participants (N = 661) were adults (aged 18+ years) in Australia with a self-reporting diagnosis of diabetes (type 1, n = 302; type 2, n = 204; prior/current gestational, n = 58; less common types, n = 22, or a family member, n = 75). Retention rates for Surveys 2 and 3 were 47% (n = 295) and 50% (n = 316), respectively. From 1549 open-text responses, 25 topics and 125 research questions were identified thematically. Research priorities differed by cohort, resulting in specific lists developed and ranked by each cohort. The top-ranked research question for the type 1 diabetes cohort was "How can diabetes technology be improved …?" and for the type 2 diabetes cohort: "How can insulin resistance be reversed …?". One question was common to the final lists of all cohorts: "What are the causes or triggers of diabetes?" Within cohorts, the top priorities were perceived as being of similar importance. CONCLUSIONS: The research priorities differ substantially by diabetes type and for family members. These findings should inform funding bodies and researchers, to align future research and its communication with community needs.

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon.

BACKGROUND: HBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AIM: To evaluate the use of serum biomarkers to predict HBeAg loss. METHODS: HBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. RESULTS: HBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03-0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67-374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18-0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. CONCLUSIONS: Baseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Financial Conflicts of Interest Among Physician Authors of ACR Appropriateness Criteria.

BACKGROUND: The accuracy and completeness of self-disclosures by authors of imaging guidelines are not well known. OBJECTIVE: The aim of this study was to assess the accuracy of financial disclosures by US authors of ACR appropriateness criteria. METHODS: We reviewed financial disclosures provided by US-based authors of all ACR-AC published in 2019, 2021 and 2023. For each US- based author, payment reports were extracted from the Open Payments Database (OPD) in the previous 36 months related to general category and research payments categories. We analyzed each author individually to determine if the reported disclosures matched results from OPD. RESULTS: A total of 633 authorships, including 333 unique authors were included from 38 ACR AC articles in 2019, with 606 authorships (387 unique authors) from 35 ACR-AC articles published in 2021, and 540 authorships (367 unique authors) from 32 ACR AC articles published in 2023. Among authors who received industry payments, failure to disclose any financial relationship was seen in 125/147 unique authors in 2019, 142/148 authors in 2021 and 95/125 unique authors in 2023. The proportion of nondisclosed total value of payments was 86.1% in 2019, 88.6% in 2021 and 56.7% in 2023. General category payments were nondisclosed in 94.1% in 2019, 89.7% in 2021 and 94.4% in 2023 by payment value. CONCLUSION: Industry payments to authors of radiology guidelines are common and frequently undisclosed.

Damage sensing through TLR9 Promotes Viral Clearance and Recovery During Influenza Infection.

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the myeloid cells and associated cytokine responses. Along with the diminished inflammatory response, the absence of damage sensing through TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza burden in the lung. The absence of TLR9 led to extensive infection of myeloid cells including monocytes and macrophages rendering them highly inflammatory, despite having a low initial inflammatory response. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/- mice. Further, we show elevated circulating TLR9 ligands in the plasma samples of patients with influenza, demonstrating its clinical relevance. Overall, over data show an essential role of damage sensing through TLR9 in promoting anti-influenza immunity.

Predicting Driver's mental workload using physiological signals: A functional data analysis approach.

This study investigates the impact of advanced driver-assistance systems on drivers' mental workload. Using a combination of physiological signals including ECG, EMG, EDA, EEG (af4 and fc6 channels from the theta band), and eye diameter data, this study aims to predict and categorize drivers' mental workload into low, adequate, and high levels. Data were collected from five different driving situations with varying cognitive demands. A functional linear regression model was employed for prediction, and the accuracy rate was calculated. Among the 31 tested combinations of physiological variables, 9 combinations achieved the highest accuracy result of 90%. These results highlight the potential benefits of utilizing raw physiological signal data and employing functional data analysis methods to understand and assess driver mental workload. The findings of this study have implications for the design and improvement of driver-assistance systems to optimize safety and performance.

Cross-cultural comparison of body dimensions and trends: an analysis of ANSUR and Size Korea datasets for automotive seating design.

The purpose of this study is to investigate the change in body dimensions over time in both Western (US) and Eastern (Korea) populations. In order to analyse the change of body dimension between the past and present and between western and eastern population, 13 body dimensions relating to automobile driver seat design were extracted from the ANSUR and Size Korea datasets at two time points, the past (ANSUR I: 1988, Size Korea: 1992) and the present (ANSUR II: 2012, Size Korea: 2012). Most of the dimensions differed significantly between past and present, as well as between the US and Korea. Overall, the data show an increasing trend of body dimensions over time for both genders. Based on the results, all countries should be encouraged to conduct periodic and national anthropometric research because body dimensions are continuously changing over time worldwide.Practitioner summary: This paper describes a study that investigates the changes in body dimensions over time in Western (US) and Eastern (Korean) populations. Findings indicate increasing trends in most dimensions for both populations, crucial for user-friendly product design and preventing hazards caused by faulty products.

Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease.

SSc-ILD (scleroderma associated interstitial lung disease) is a complex rheumatic disease characterized in part by immune dysregulation leading to the progressive fibrotic replacement of normal lung architecture. Because improved treatment options are sorely needed, additional study of the fibroproliferative mechanisms mediating this disease has the potential to accelerate development of novel therapies. The contribution of innate immunity is an emerging area of investigation in SSc-ILD as recent work has demonstrated the mechanistic and clinical significance of the NLRP3 inflammasome and its associated cytokines of TNFα (tumor necrosis factor alpha), IL-1ß (interleukin-1 beta), and IL-18 in this disease. In this review, we will highlight novel pathophysiologic insights afforded by these studies and the potential of leveraging this complex biology for clinical benefit.

Nascent Aß42 Fibrillization in Synaptic Endosomes Precedes Plaque Formation in a Mouse Model of Alzheimer's-like ß-Amyloidosis.

Accumulation of amyloid-ß peptide (Aß) aggregates in synapses may contribute to the profound synaptic loss characteristic of Alzheimer's disease (AD). The origin of synaptic Aß aggregates remains elusive, but loss of endosomal proteostasis may trigger their formation. In this study, we identified the synaptic compartments where Aß accumulates, and performed a longitudinal analysis of synaptosomes isolated from brains of TgCRND8 APP transgenic mice of either sex. To evaluate the specific contribution of Aß-degrading protease endothelin-converting enzyme (ECE-1) to synaptic/endosomal Aß homeostasis, we analyzed the effect of partial Ece1 KO in brain and complete ECE1 KO in SH-SY5Y cells. Global inhibition of ECE family members was used to further assess their role in preventing synaptic Aß accumulation. Results showed that, before extracellular amyloid deposition, synapses were burdened with detergent-soluble Aß monomers, oligomers, and fibrils. Levels of all soluble Aß species declined thereafter, as Aß42 turned progressively insoluble and accumulated in Aß-producing synaptic endosomal vesicles with characteristics of multivesicular bodies. Accordingly, fibrillar Aß was detected in brain exosomes. ECE-1-deficient mice had significantly increased endogenous synaptosomal Aß42 levels, and protease inhibitor experiments showed that, in TgCRND8 mice, synaptic Aß42 became nearly resistant to degradation by ECE-related proteases. Our study supports that Aß accumulating in synapses is produced locally, within endosomes, and does not require the presence of amyloid plaques. ECE-1 is a determinant factor controlling the accumulation and fibrillization of nascent Aß in endosomes and, in TgCRND8 mice, Aß overproduction causes rapid loss of Aß42 solubility that curtails ECE-mediated degradation.SIGNIFICANCE STATEMENT Deposition of aggregated Aß in extracellular plaques is a defining feature of AD. Aß aggregates also accumulate in synapses and may contribute to the profound synaptic loss and cognitive dysfunction typical of the disease. However, it is not clear whether synaptotoxic Aß is mainly derived from plaques or if it is produced and aggregated locally, within affected synaptic compartments. Filling this knowledge gap is important for the development of an effective treatment for AD, as extracellular and intrasynaptic pools of Aß may not be equally modulated by immunotherapies or other therapeutic approaches. In this manuscript, we provide evidence that Aß aggregates building up in synapses are formed locally, within synaptic endosomes, because of disruptions in nascent Aß proteostasis.

PARK7 Catalyzes Stereospecific Detoxification of Methylglyoxal Consistent with Glyoxalase and Not Deglycase Function.

The protein PARK7 (also known as DJ-1) has been implicated in several diseases, with the most notable being Parkinson's disease. While several molecular and cellular roles have been ascribed to DJ-1, there is no real consensus on what its true cellular functions are and how the loss of DJ-1 function may contribute to the pathogenesis of Parkinson's disease. Recent reports have implicated DJ-1 in the detoxification of several reactive metabolites that are produced during glycolytic metabolism, with the most notable being the α-oxoaldehyde species methylglyoxal. While it is generally agreed that DJ-1 is able to metabolize methylglyoxal to lactate, the mechanism by which it does so is hotly debated with potential implications for cellular function. In this work, we provide definitive evidence that recombinant DJ-1 produced in human cells prevents the stable glycation of other proteins through the conversion of methylglyoxal or a related alkynyl dicarbonyl probe to their corresponding α-hydroxy carboxylic acid products. This protective action of DJ-1 does not require a physical interaction with a target protein, providing direct evidence for a glutathione-free glyoxalase and not a deglycase mechanism of methylglyoxal detoxification. Stereospecific liquid chromatography-mass spectrometry (LC-MS) measurements further uncovered the existence of nonenzymatic production of racemic lactate from MGO under physiological buffer conditions, whereas incubation with DJ-1 predominantly produces l-lactate. Collectively, these studies provide direct support for the stereospecific conversion of MGO to l-lactate by DJ-1 in solution with negligible or no contribution of direct protein deglycation.

Applying the Accumulator model to predict driver's reaction time based on looming in approaching and braking conditions.

INTRODUCTION: The prediction of when the driver will react to a change in the lead vehicle motion is critical for assessing rear-end crash risk using car-following models. Past studies have assumed constant reaction time and driver's continuous reaction. However, these assumptions are not valid as the driver's reaction time can vary in different car-following situations and the driver does not continuously react to the lead vehicle motion. Thus, this study predicted the driver's reaction time using the Wiedemann car-following model and the Accumulator model. The Accumulator model assumes the driver's start of reaction based on the accumulation of looming and thereby reflects the driver's intermittent reaction. METHOD: Fifty drivers' behavior was observed using a driving simulator in two scenarios: (1) approach and follow a moving lead vehicle and (2) approach a stopped lead vehicle. The Accumulator model predicted the reaction times based on different looming variables (angular velocity and tau-inverse), lead vehicle type (car and truck), and lead vehicle brake lights (on or off). RESULTS: The Accumulator model showed lower prediction errors of the reaction time than the Wiedemann model, which assumes reaction based on the fixed looming threshold. The Accumulator model predicted the reaction times more accurately when it was calibrated with the angular velocity due to width and height of lead vehicles. Moreover, the Accumulator model with tau-inverse produced the smallest prediction error of reaction times among different Accumulator models and the Wiedemann model when lead vehicle brake lights were on. CONCLUSIONS: This study demonstrates that the Accumulator model is a promising method of predicting the driver's reaction time in car-following situations, which affects rear-end crash risk. PRACTICAL APPLICATIONS: The Accumulator model can be incorporated into a car-following model for the prediction of reaction times and can estimate the rear-end collision risk of vehicles more accurately.