Pilot Safety Research Articles

Learning-Based Stochastic Driving Model for Autonomous Vehicle Testing

In the simulation-based testing and evaluation of autonomous vehicles (AVs), how background vehicles (BVs) drive directly influences the AV’s driving behavior and further affects the test results. Most existing simulation platforms use either predetermined trajectories or deterministic driving models to model BV behaviors. However, predetermined BV trajectories cannot react to AV maneuvers, and deterministic models are different from real human drivers because of the lack of stochastic components and errors. Both methods lead to unrealistic traffic scenarios. This paper presents a learning-based stochastic driving model that meets the unique needs of AV testing (i.e., interactive and human-like stochasticity). The model is built based on the long short-term memory architecture. By incorporating the concept of quantile regression into the loss function of the model, the stochastic behaviors are reproduced without prior assumption of human drivers. The model is trained with the large-scale naturalistic driving data (NDD) from the Safety Pilot Model Deployment project and compared with a stochastic intelligent driving model (IDM). Analysis of individual trajectories shows that the proposed model can reproduce more similar trajectories of human drivers than IDM. To validate the ability of the proposed model in generating a naturalistic driving environment, traffic simulation experiments are implemented. The results show that traffic flow parameters such as speed, range, and time headway distribution match closely with the NDD, which is of significant importance for AV testing and evaluation.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial

SummaryBackgroundTyphoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings.MethodsWe did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110.Findings41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI −12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed.InterpretationVi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses.FundingThe study was funded by the Bill & Melinda Gates Foundation.

Online distraction detection for naturalistic driving dataset using kinematic motion models and a multiple model algorithm

Detecting distracted driving is important for developing Advanced Driver Assistance Systems and improving road safety. Most of the existing research analyzes drivers directly via video analysis techniques or by measuring cognitive load, however these approaches often require additional sensors to be installed in vehicles or equipped to drivers. Given that most distractions may have a direct influence on drivers’ control of vehicles, this paper proposes a new method to utilize available vehicle kinematic data for detecting distracted driving. The proposed method predicts vehicle kinematics by fusing multiple state–space models that capture different driving motion patterns under normal driving. An online monitoring scheme is developed by using Exponentially Weighted Moving Average (EWMA) and Cumulative Sum (CUSUM) charts, which detects abnormal mean shifts of lateral speeds and prediction errors of lane positions to provide warnings of distracted driving. A case study is presented based on two naturalistic driving datasets — the Integrated Vehicle-Based Safety Systems (IVBSS) and Safety Pilot Model Deployment (SPMD) datasets.

Pilot Safety Study of an Extracellular Vesicle Isolate Product for Treatment of Osteoarthritis in Combat-Related Injuries: One Year Follow Up

Objective: This is the first report on the safety and clinical efficacy of a bone marrow mesenchymal cell extracellular vesicle isolate product (XoFlo™) to treat osteoarthritis (OA). Design, Setting, and Methods: Thirty-three Navy SEAL ..

Supplement Yogurt for Patients during Early Phase of Unrelated Cord Blood Transplantation: A Safety and Feasibility Pilot Study

Background: During last few years, intestinal microbiota, as a vital biological regulatory substance after hematopoietic stem cell transplantation (HSCT), has been attached with growing importance. Probiotics in yogurt may have positive effect in protecting intestinal microbiota diversity and improving the prognosis of patients after HSCT. However, the safety of supplement yogurt has not been evaluated in the early phase of HSCT. In order to evaluate the safety and feasibility of yogurt, we conducted a pilot study in patients who had undergone unrelated cord blood transplantation (UCBT).Method: Between February and June 2017, patients receiving UCBT was divided into two groups randomly. The experimental group (20 patients; mean age 17y, r 1-59; male 11) and control group (26 patients; mean age 24.3y, r 1-59; male 12) have no significant differences in age, gender, weight, underlying diseases and conditioning intensity (Table 1). Patients in experimental group (n=20) take in 200ml yogurt while children take in 100ml every day on day -7 and continue until day +30 (xinxiwang yogurt, including lactobacillus bulgaricus, streptococcus thermophilus, lactobacillus plantarum, lactobacillus rhamnosus, the number of lactobacillus≥108CFU/100g, produced at Jinrong Road 33rd, Shuangfeng economic industrial zone, Changfeng, Hefei, Anhui), while patients in control group (n=26) taking in nothing. All patients received CsA plus mycophenolate mofetil as GVHD prophylaxis.Results: we compared some indicators related to UCBT between the two group (Table 2). The primary engraftment rate is 95.0% (experimental group) and 96.2% (control group). The mortality in 60 day is 10% and 7.7% and the median time to 0.5×109/L ANC was 17 days (r 12-30) and 18.5 days(r 12-24). The incidence of acute GVHD gradeⅠ-Ⅳ (55.0% vs.57.7%, P= 0.972), bacteremia (45.0% vs.46.2%, P= 0.972), diarrhea (35.0% vs.53.8%, P= 0.444), and pre-engraftment syndrome (55.0% vs.80.8%, P= 0.154) show no significant differences between two group. While, the continuous change of CRP (P= 0.343), weight(P= 0.738), and albumin(P= 0.345) from day -7 to day +30 is also no significant difference between two groups. We don't observe any case of lactobacillus bacteremia (0%) in experimental group, together with none occurrence of lactobacillus-related unexpected adverse events through the whole study.Conclusion: Our data show it is safe and feasible to supplement yogurt during early phase of unrelated cord blood transplantation. It will not result in an increasing related risks including infection, diarrhea, aGVHD, and also not influence the nutritional status of patients. However, due to the limitation of the number of cases and short observation duration, we can not evaluate the effectiveness of the supplement yogurt. Further conclusion requires larger sample size and longer observation duration.No conflict of interest to declare. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety analysis of the optionally-piloted airplane landing

PurposeThis study aims to optionally-piloted aircraft is useful for in-flight tests of new automatic controller’s concepts. The safety of this kind of experiment is an issue addressed in this paper. The prediction of possible safety-influencing factors makes it possible to assess the pilot’s ability to effectively prevent safety risks.Design/methodology/approachThe analysis in this research paper focusses on two cases of monitoring; similar control standards for both pilot in command and the monitoring pilot or technical systems in one of these tasks and dissimilar control standard when monitoring pilot is not familiar with a control manner of the pilot in command or of the automatic control system. The increased workload is expected in the last case as the result of additional activities determined theoretically in the presented analysis. Details of the possible threats are obtained by simulation tests with various factors influencing the safety of landing. In addition to determining threats, the analysis includes the possibility of in time threat detection and preserving action.FindingsThe results show that the safety pilot has a different task than the pilot in command and needs to be familiar with the general principles of automatic controller operations and the particular algorithm being tested. Although commonly used landing procedure is relatively error-tolerant, new landing procedures for use in some specific conditions need more precise control and additional safety pilot preparation. Additional information presented to both the pilot in command and the safety pilot may increase mode and state awareness and reduce reaction time in an emergency condition.Practical implicationsIn-flight tests of non-standard control algorithms there is a need to include additional preparation of the equipment and safety pilot. The research in this paper illustrates how to determine threats and safety-critical moments during the experimental flight can be observed. The danger is mitigated by the safety pilot, if familiar with both proper and improper operations of the controller and how the pilot in command should detect and predict danger caused by the tested control system.Originality/valueThe presented method of analysis combines the human factor with various technical aspects. The results obtained illustrate the real tasks of the person supervising the operation of the automatic control system and the role of a human as a safety pilot.

Constructing spatiotemporal driving volatility profiles for connected and automated vehicles in existing highway networks

Connected and automated vehicles (CAVs) are expected to change the way we travel. Before both the vehicles and infrastructures are fully automated, users of CAVs are required to respond appropriately to any adverse on-road conditions or malfunction that may prevent the autonomous driving system from reliably sustaining the dynamic driving task performance. The objective of this study is to construct spatiotemporal driving volatility profiles to help CAVs or drivers identify the potential hazards in the existing transportation network and make proactive driving decisions. The volatility profiles are constructed based on the historical traffic dynamics, varying spatially and temporally in the network. For demonstration, this study exploited the Basic Safety Messages datasets from Safety Pilot Model Development program in Ann Arbor, Michigan. The driving volatility is a measure to reflect the variability of driving performance, which is often used to show a vehicle or driver’s performance on road. This study extends the concept to capture the driving dynamics as a performance of the transportation network. This study also matched the driving volatility to the spatial and temporal occurrence of historical traffic crashes. Modeling results showed the volatility is significantly related to safety outcomes; therefore, the driving volatility profiles can be compiled into the high definition (HD) maps to inform CAVs and drivers of potential on-road hazards and assisting in making proactive driving decisions. Further, the results offer implications for potential upgrades of the transportation infrastructure for full automation in the future.

Driving Style Recognition under Connected Circumstance Using a Supervised Hierarchical Bayesian Model

In recent years, the automated driving system has been known to be one of the most popular research topics of artificial intelligence (AI) and intelligent transportation system (ITS). The journey experience on automated vehicles and the intelligent automated driving system could be improved by individualization driving understanding. Although previous studies have proposed methods for driving styles understanding, the individualization driving classification has not been addressed thoroughly. Therefore, in this study, a supervised method is proposed to understand driving behavioral structure and the latent driving styles by incorporating the prior knowledge. Firstly, a novel method is established for driving behavioral encoding and raw driving data mining. Then, the Labeled Latent Dirichlet Allocation (LLDA) is proposed to understand the latent driving styles from individual driving with driving behaviors. Finally, the Safety Pilot Model Deployment (SPMD) data are used to validate the performance of the proposed model. Experimental results show that the proposed model uncovers latent driving styles effectively and shows good agreement to real situations, which provides theoretical guidance on driving behavior recognition for better individual experience on automated driving vehicles.

An Open, Uncontrolled Pilot Study on 12-Week Use of VagiVital for Treatment of VulvovaginalAtrophy in Breast Cancer Patients Undergoing Adjuvant Aromatase-Inhibitor Therapy.

PurposeThis pilot study assessed the efficacy of 12 weeks of daily treatment with a vaginal gel based on a water-based cellulose gel in reducing the severity of moderate–severe symptoms of vulvovaginal atrophy (VVA) and followed adverse events in female breast cancer patients undergoing treatment with adjuvant aromatase- inhibitor therapy.MethodsIn this open, uncontrolled pilot study, the efficacy and safety of the gel during a treatment period of 12 weeks (daily 1×1 mL) were evaluated (n=28). The gel is made of water and hypromellose, a hydropropylmetyl cellulose, which works by coating the vagina, and was developed to treat moderate–severe symptoms of VVA. The primary efficacy variable was the most bothersome symptom (MBS; among vulvovaginal irritation and itching, vaginal dryness, dysuria, or dyspareunia) self-identified at baseline on a four-point scale.ResultsA total of 28 patients fulfilled all entry criteria and had data available after the start of treatment. Treatment with the gel reduced MBS scores from baseline (n=28, mean 2.71) to week 12 (n=27, mean 1.33, mean reduction 1.37; p=0), and reduced the overall total scores for VVA symptoms from a mean of 5.39 at baseline to 2.25 at week 12 (p=0). Eleven subjects (39%) reported 19 AEs.ConclusionA 12-week treatment with the gel significantly reduced the severity of MBSs and VVA symptoms, improved quality of life, and was safe to use in women with breast cancer undergoing adjuvant aromatase-inhibitor therapy. In view of the beneficial effects of nonhormonal treatments, for cancer patients in particular, the water-based cellulose gel VagiVital is a suitable candidate for first-choice treatment of VVA symptoms in breast cancer patients and in women predisposed to cancer.

Prophylactic intravenous gentamicin with sedation-free cystoscopic injection of BoNT-A: No demonstrable adverse extravesical neuromuscular effects in a pilot safety study of 220 idiopathic overactive bladder patients

Objectives: To determine whether administration of single dose prophylactic intravenous gentamicin prior to intravesical injection of botulinum toxin type A (BoNT-A) is associated with adverse extravesical neuromuscular effects in idiopathic overactive bladder syndrome. Patients and methods: A retrospective analysis of 220 consecutive idiopathic overactive bladder patients following sedation-free flexible cystoscopic injection of intravesical BoNT-A. All patients received a single dose of intravenous gentamicin (160 mg) followed by 100-200 IU of BoNT-A. They were followed up at intervals to determine whether they had experienced any adverse extravesical neuromuscular side effects. Results: None of our patients developed adverse extravesical neuromuscular side effects from intravesical botulinum injections with concomitant administration of intravenous gentamicin. Conclusion: Single dose intravenous gentamicin is safe to use as a prophylaxis for intravesical BoNT-A injections of 200 IU or below in idiopathic overactive bladder patients. Level of evidence: Not applicable.

Hidden Markov Model of Lane-Changing-Based Car-Following Behavior on Freeways using Naturalistic Driving Data

This paper develops a methodology for simultaneously modeling lane-changing and car-following behavior of automated vehicles on freeways. Naturalistic driving data from the Safety Pilot Model Deployment (SPMD) program are used. First, a framework to process the SPMD data is proposed using various data analytics techniques including data fusion, data mining, and machine learning. Second, pairs of automated host vehicle and their corresponding front vehicle are identified along with their lane-change and car-following relationship data. Using these data, a lane-changing-based car-following (LCCF) model, which explicitly considers lane-change and car-following behavior simultaneously, is developed. The LCCF model is based on Gaussian-mixture-based hidden Markov model theory and is disaggregated into two processes: LCCF association and LCCF dissociation. These categories are based on the result of the lane change. The overall goal is to predict a driver’s lane-change intention using the LCCF model. Results show that the model can predict the lane-change event in the order of 0.6 to 1.3 s before the moment of the vehicle body across the lane boundary. In addition, the execution times of lane-change maneuvers average between 0.55 and 0.86 s. The LCCF model allows the intention time and execution time of driver’s lane-change behavior to be forecast, which will help to develop better advanced driver assistance systems for vehicle controls with respect to lane-change and car-following warning functions.

The role of drivers’ social interactions in their driving behavior: Empirical evidence and implications for car-following and traffic flow

Models for describing the microscopic driving behavior rarely consider the “social effects” on drivers’ driving decisions. However, social effect can be generated due to interactions with surrounding vehicles and affect drivers’ driving behavior, e.g., the interactions result in imitating the behavior of peer drivers. Therefore, social environment and peer influence can impact the drivers’ instantaneous behavior and shift the individuals’ driving state. This study aims to explore empirical evidence for existence of a social effect, i.e., when a fast-moving vehicle passes a subject vehicle, does the driver mimic the behavior of passing vehicle? High-resolution Basic Safety Message data set (N = 151,380,578) from the Safety Pilot Model Deployment program in Ann Arbor, Michigan, is used to explore the issue. The data relates to positions, speeds, and accelerations of 63 host vehicles traveling in connected vehicles with detailed information on surrounding environment at a frequency of 10 Hz. Rigorous random parameter logit models are estimated to capture the heterogeneity among the observations and to explore if the correlates of social effect can vary both positively and negatively. Results show that subject drivers do mimic the behavior of passing vehicles –in 16 percent of passing events (N = 18,099 total passings occurred in freeways), subject vehicle drivers are observed to follow the passing vehicles accelerating. We found that only 1.2 percent of drivers normally sped up (10 km/hr in 10 s) during their trips, when they were not passed by other vehicles. However, if passed by a high speed vehicle the percentage of drivers who sped up is 16.0 percent. The speed change of at least 10 km/hr within 10 s duration is considered as accelerating threshold. Furthermore, the acceleration of subject vehicle is more likely if the speed of subject driver is higher and more surrounding vehicles are present. Interestingly, if the difference with passing vehicle speed is high, the likelihood of subject driver’s acceleration is lower, consistent with expectation that if such differences are too high, the subject driver may be minimally affected. The study provides new evidence that drivers’ social interactions can change traffic flow and implications of the study results are discussed.

Longevity of the novel ConvaTec infusion set with Lantern technology.

Current insulin infusion sets are approved for only 2-3 days. The novel ConvaTec infusion set with Lantern technology is designed to extend infusion set wear time. The goal of this pilot study was to evaluate the duration of wear for this set. This was a pilot safety study in adults with type 1 diabetes using tethered insulin pumps. Participants inserted the set and wore it for 10 days or until failure. Among 24 participants, two were excluded. Forty-five per cent of the sets lasted 10 days. Median wear time was 9.1 (7.1, 10.0) days. Among 12 premature failures, six (50%) involved adhesive failures, four (33%) hyperglycaemia unresponsive to correction, one (8%) hyperglycaemia with ketones and one (8%) infection. Average CGM glucose per day of infusion set wear showed a statistically significant increase over time, while total daily insulin over the same period did not change. In this pilot study, the duration of wear for the novel infusion set exceeded previously reported commercial sets (P < .001). This extended wear technology may eventually allow for a combined glucose sensor and infusion set.

Teleglaucoma Initiative at a Veterans Affairs Hospital: Pilot Safety Data and Early Experience

To evaluate the safety, reliability, and efficacy of telemedicine in delivering tertiary subspecialty glaucoma care (herein referred to as teleglaucoma) to the veteran patient population. Prospective case series. Twenty patients being referred for glaucoma subspecialist opinion participated in the pilot safety study. One hundred eighteen patients participated in the secondary study of the acceptability and service efficacy of teleglaucoma. In the pilot study, safety was assessed by determining interobserver and intraobserver consistency (Krippendorff's α). This compared an in-person assessment by a glaucoma subspecialist with the remote assessment of 2 other glaucoma subspecialists (electronic health record alone reviewed). In the secondary study, teleglaucoma was implemented whereby testing and eye examination were carried out remotely by an optometrist or comprehensive ophthalmologist, and the clinical decision was made by the glaucoma subspecialist on review of the electronic health record alone. In the pilot study, interobserver and intraobserver consistency in making a diagnosis and treatment plan (acceptable, ≥ 0.80 Krippendorff's α). In the secondary study, patient satisfaction measured by survey, wait time for teleglaucoma opinion versus wait time for in-person opinion, and time spent on teleglaucoma consultations. Interobserver and intraobserver consistency showed an α of 0.86 and 0.92, respectively, for diagnosis, and 0.86 and 0.85, respectively, for treatment plan. In the secondary study, patient satisfaction was 4.55 of 5.00 (5= maximum satisfaction; range, 3.28-4.93). Improved consultation lead time was demonstrated, with the median time for a doctor to respond to an electronic consultation being 3 days, versus 43 days for an in-person visit. Teleglaucoma also demonstrated positive benefits to the health care system by reducing the time doctors spent reviewing each patient's case (history, examination findings, imaging results, visual fields; 19 minutes for teleglaucoma consultation vs. 31 minutes for in-person evaluation). Decisions regarding diagnoses and treatment plans between in-person consultation and the teleglaucoma program showed high reliability. Patient satisfaction was high. Additional benefits were observed in wait time for subspecialty glaucoma opinion, efficient allocation of the doctor's time, and fiscal benefit to the health care system.

A Sun Safety Pilot Program Using a Tanning Myths–Focused Video Contest for Utah Adolescents: Cross-sectional Analysis

BackgroundAdolescents are susceptible to excessive ultraviolet exposure due to intentional tanning, outdoor lifestyles, and poor sunscreen adherence. As skin cancer incidence continues to rise in the United States, effective and focused interventions are needed to encourage photoprotective behaviors.ObjectiveThis study seeks to determine poor photoprotective behavior risk factors in adolescents residing in Utah and whether video contest participants have increased sun-protective knowledge and intentions.MethodsIn this cross-sectional study, we surveyed Utah high school students (n=20) who participated in a tanning myths-themed public service announcement video contest. A control cohort of students who did not participate in the video contest were also surveyed (n=89). Demographics, sun exposure history, intentions to tan, and intentions to use sunscreen were documented. Knowledge of tanning myths was assessed with a 7-question sun safety quiz.ResultsThe survey response rate was 93.2% (109/117). Two-thirds reported at least one sunburn, and 47.7% (52/109) reported intentional tanning within the past 2 years. Higher tanning intentions were associated with a personal (P&lt;.001), family (P=.001), and peer (P&lt;.001) history of tanning. Video contest participants had higher sun safety quiz scores (P&lt;.001) and higher sunscreen use intentions (P=.01), but did not have decreased tanning intentions (P=.47) compared to non–video contest participants. Hispanic and Black students were less likely to participate in the video contest (P&lt;.001 and P=.04, respectively). In a comparison of White students to students of color, there were no differences in sun exposure history, but students of color had lower sun safety knowledge (P=.01) and lower sunscreen use intention (P=.02).ConclusionsSun safety educational disparities exist, and targeted efforts are needed to encourage photoprotective behaviors in high-risk populations. Our findings suggest that video contest participation may encourage sunscreen use and sun protection awareness.

Autologous Bone Marrow Aspirate Stem Cell Concentrate (BMAC) for treatment of patients with Fontaine stages III-IV peripheral arterial disease: a pilot safety and feasibility study

Autologous Bone Marrow Aspirate Stem Cell Concentrate (BMAC) for treatment of patients with Fontaine stages III-IV peripheral arterial disease: a pilot safety and feasibility study

Examining the most accident-prone sector within commercial aviation: Why do accidents with light inland helicopters occur, and how can we improve safety?

Light inland helicopter has for several years been the most accident-prone sector within commercial aviation, with a more than 10 times higher accident risk than offshore helicopters. The main aims of this article are to: 1) Examine why accidents with light inland helicopters occur, focusing especially on the situation in Norway, but also internationally and 2) discuss how these accidents can be prevented. These questions are examined based on three data sources: 1) Analysis of reports from the Accident Investigation Board Norway (AIBN), 2) Qualitative expert interviews, and 3) Systematic literature review. Most of the reviewed studies point to combinations of human errors and technical failures as the major risk factors contributing to helicopter accidents. Our analysis contributes to existing research by also indicating the critical importance of work-related factors like inadequate safety management systems, poor safety culture and challenging framework conditions for pilot behaviour and safety. The literature review indicates a lack of robustly evaluated helicopter safety interventions to address the identified risk factors. Our analysis of the AIBN reports and the interviews indicates a need for measures aiming to improve the safety culture in a sector with challenging framework conditions. Measures focusing on the development of self-imposed and commonly accepted operational limits and guidelines in the sector are discussed.

Rose Bengal Photodynamic Antimicrobial Therapy: A Pilot Safety Study.

To evaluate the in vivo corneal changes after Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) treatment in New Zealand White rabbits. Sixteen rabbits were divided into 5 groups. All groups underwent deepithelialization of an 8 mm diameter area in the central cornea. Group 1: balanced salt solution drops only, group 2: 0.2% RB only, group 3: green light exposure (525 nm, 5.4 J/cm2) only, group 4: 0.1% RB-PDAT, and group 5: 0.1% RB-PDAT. All rabbits were followed clinically. Group 5 rabbits were followed using anterior segment optical coherence tomography (AS-OCT) and clinically. On day 35 after initial treatment, 1 rabbit from group 5 was re-exposed to green light (5.4 J/cm2) to evaluate reactivation of the remaining RB dye, and terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling assay was performed on corneal cryosections. Complete reepithelization was observed, and corneas remained clear after treatment in all groups. In group 5, AS-OCT revealed a cross-linking demarcation line. AS-OCT showed RB fluorescence and collagen cross-linking in all treated eyes of group 5 animals after 5 weeks of treatment. Photobleached RB retention in the corneal stroma was corroborated by fluorescence confocal microscopy on frozen sections. There was no evidence of a sustained cytotoxic effect through terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling at 5 weeks. RB-PDAT with 0.1% RB is a safe procedure. There was no difference clinically and on histopathology compared with control groups. In eyes where RB dye is retained in the corneal stroma after 1 month of treatment, oxidative stress is not evidenced at long term.

Treatment of distal unruptured intracranial aneurysms using a surface-modified flow diverter under prasugrel monotherapy: a pilot safety trial

BackgroundFlow diverters (FDs) are effective in the treatment of carotid aneurysms. Compared with carotid aneurysms, the treatment of distal intracranial aneurysms with FDs has been associated with a relatively high...

Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation.

Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as preliminary preclinical hECP safety. Optimized cell banking workflows were proposed, potentially generating millions of safe and sustainable therapeutic products. Furthermore, clinical hECP doses were characterized as non-toxic in a standardized chorioallantoic membrane model. Lastly, a MACI-like protocol, including hECPs, was applied in a three-month GLP pilot safety evaluation in a caprine model of full-thickness articular cartilage defect. The safety of hECP transplantation was highlighted in xenogeneic settings, along with confirmed needs for optimal cell delivery vehicles and implantation techniques favoring effective cartilage repair or regeneration.