Detection of Risky Driving Behaviors in the Naturalistic Environment in Healthy Older Adults and Mild Alzheimer’s Disease

Analyzing naturalistic driving behavior recorded with in-car cameras is an ecologically valid method for measuring driving errors, but it is time intensive and not easily applied on a large scale. This study validated a semi-automated, computerized method using archival naturalistic driving data collected for drivers with mild Alzheimer’s disease (AD; n = 44) and age-matched healthy controls (HC; n = 16). The computerized method flagged driving situations where safety concerns are most likely to occur (i.e., rapid stops, lane deviations, turns, and intersections). These driving epochs were manually reviewed and rated for error type and severity, if present. Ratings were made with a standardized scoring system adapted from DriveCam®. The top eight error types were applied as features to train a logistic model tree classifier to predict diagnostic group. The sensitivity and specificity were compared among the event-based method, on-road test, and composite ratings of two weeks of recorded driving. The logistic model derived from the event-based method had the best overall accuracy (91.7%) and sensitivity (97.7%) and high specificity (75.0%) compared to the other methods. Review of driving situations where risk is highest appears to be a sensitive data reduction method for detecting cognitive impairment associated driving behaviors and may be a more cost-effective method for analyzing large volumes of naturalistic data

An investigation of perceived vehicle speed from a driver's perspective

Purpose Speed estimation of drivers’ own vehicles and other vehicles on the road is an important task for drivers and is also crucial to the roadway safety. The objective of the study was to examine the effects of multiple factors such as image scale, speed, road type, driving experience, and gender on the speed perception of drivers’ own vehicles. Methods: Thirty participants consisted of 17 males and 13 females, including 13 without driving experience. All participants estimated the driving speed of 192 5-second video clips, which were selected from naturalistic driving recordings. The recorded driving speeds were evenly distributed across the entire range from 5mph to 65mph. Half of the selected video clips were recorded on wide roads and another half were recorded on comparatively narrow roads. Video clips were played on a large screen, with each clip shown in one of 4 image scales (100%, 75%, 50%, and 38% of the actual field of view in the real world). Results: Speed estimates were most accurate for the smallest image size (38% of the actual field of view). As the image size increased, the driving speed was increasingly underestimated. Participants with driving experience accurately estimated the driving speed on both wide and narrow roads whereas those without driving experience had greater underestimates on wider roads. Speeds were most accurately estimated within the range 25-35mph, but the speeds slower than the range tend to be overestimated and the speeds faster than the range are more likely to be underestimated. While males and females showed the same pattern across speed groups, females have greater estimation errors at the highest and lowest speed groups. Participants without driving experience showed increasing underestimation of speed as driving speed increased whereas participants with driving experience primarily underestimated the highest speeds. Conclusions: The present study shows the effect of multidimensional influential factors on perceived vehicle speed from drivers’ perspective. The results also have implications for driving simulation scenario design, driving simulator setup, and the assessment of speed control in simulated and naturalistic environments

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Object Recognition

Vision-based object recognition tasks are very familiar in our everyday activities, such as driving our car in the correct lane. We do these tasks effortlessly in real-time. In the last decades, with the advancement of computer technology, researchers and application developers are trying to mimic the human's capability of visually recognising. Such capability will allow machine to free human from boring or dangerous jobs

Examining epigenetic variation in the brain in mental illness

Mental health represents one of the most significant and increasing burdens to global public health. Depression and schizophrenia, among other mental illnesses, constitute strong risk factors for suicidality which results in over 800,000 deaths every year. The majority of suicides worldwide are indeed related to psychiatric diseases. A growing body of genetic, epigenetic and epidemiological evidence suggests that psychiatric disorders are highly complex phenotypes originating from the multilevel interplay between the strong genetic component and a range of environmental and psychosocial factors. Deeper understanding about the biology of the genome has led to increased interest for the role of non-sequence-based variation in the etiology of neuropsychiatric phenotypes, including suicidality. Epigenetic alterations and gene expression dysregulation have been repetitively reported in post-mortem brain of individuals who died by suicide. To date, however, studies characterizing disease-associated methylomic and transcriptomic variation in the brain have been limited by screening performed in bulk tissue and by the assessment of a single marker at a time. The main aim of this thesis was to investigate DNA methylation and miRNA expression differences in post-mortem brain associated with suicidality and unravel the complexity of epigenetic signals in a heterogeneous tissue like the human brain by developing a method to profile genomic variation at the resolution of individual neural cell types. The results here reported, provide further support for a suicide-specific epigenetic signature, independent from comorbidity with other psychiatric phenotypes, as well as confirming the strong bias perpetrated by bulk tissue studies hence the need to examine genomic variations in purified cell types. In summary, this thesis has identified a) a suicide-specific signal in two different epigenetic markers (DNA methylation and miRNA expression) and b) a protocol to simultaneously profile DNA methylation levels across three purified cell types in the healthy brain highlighting the utility of cell sorting for identifying cell type-driven epigenetic differences associated with etiological variation in complex psychiatric phenotypes.1) ARUK-PPG2018A-010 – “Developing approaches to address neural cell heterogeneity in genomic studies of Alzheimer's disease”. 2) SBF001\1011 - “Using functional epigenomics to dissect the molecular architecture of schizophrenia

Diagnostic Significance of Exosomal miRNAs in the Plasma of Breast Cancer Patients

Poster Session AbstractsBackground and Aims: Emerging evidence that microRNAs (miRNAs) play an important role in cancer development has opened up new opportunities for cancer diagnosis. Recent studies demonstrated that released exosomes which contain a subset of both cellular mRNA and miRNA could be a useful source of biomarkers for cancer detection. Here, we aim to develop a novel biomarker for breast cancer diagnosis using exosomal miRNAs in plasma. Methods: We have developed a rapid and novel isolation protocol to enrich tumor-associated exosomes from plasma samples by capturing tumor specific surface markers containing exosomes. After enrichment, we performed miRNA profiling on four sample sets; (1) Ep-CAM marker enriched plasma exosomes of breast cancer patients; (2) breast tumors of the same patients; (3) adjacent non-cancerous tissues of the same patients; (4) Ep-CAM marker enriched plasma exosomes of normal control subjects. Profiling is performed using PCR-based array with human microRNA panels that contain more than 700 miRNAs. Results: Our profiling data showed that 15 miRNAs are concordantly up-regulated and 13 miRNAs are concordantly down-regulated in both plasma exosomes and corresponding tumors. These account for 25% (up-regulation) and 15% (down-regulation) of all miRNAs detectable in plasma exosomes. Our findings demonstrate that miRNA profile in EpCAM-enriched plasma exosomes from breast cancer patients exhibit certain similar pattern to that in the corresponding tumors. Based on our profiling results, plasma signatures that differentiated breast cancer from control are generated and some of the well-known breast cancer related miRNAs such as miR-10b, miR-21, miR-155 and miR-145 are included in our panel list. The putative miRNA biomarkers are validated on plasma samples from an independent cohort from more than 100 cancer patients. Further validation of the selected markers is likely to offer an accurate, noninvasive and specific diagnostic assay for breast cancer. Conclusions: These results suggest that exosomal miRNAs in plasma may be a novel biomarker for breast cancer diagnosis.link_to_OA_fulltex

FIRST LINE AVELUMAB IN PD-L1+VE METASTATIC OR LOCALLY ADVANCED UROTHELIAL CANCER (AUC) PATIENTS UNFIT FOR CISPLATIN (CIS): THE ARIES TRIAL

Background: Avelumab (ave) was approved as maintenance therapy after platinum-based first line (1L) therapy for patients (pts) with aUC based on ph. 3 Javelin Bladder 100 study (NCT02603432), showing significant overall survival (OS) improvement. Here we tested the activity of ave as 1L of therapy in pts with aUC and PD-L1+ve expression. Methods: ARIES is a single-arm, multi-site, open-label phase II trial. Enrolled pts had aUC, were cis-unfit (at least one of: ECOG-PS=2, CrCl <60 mL/min, grade ⩾2 peripheral neuropathy/hearing loss, progression within 6-mos before the end of neo/adj chemo), had not previously received chemo for aUC and PD-L1⩾5% (SP263) centrally assessed. Pts received ave 10 mg/Kg IV Q2W until progression, unacceptable toxicity and withdrawal, whichever occurred first. The primary endpoint was the 1-year OS. Key secondary endpoints were median-OS, -PFS, ORR, DOR and safety. The outcome based on PDL1 expression >10 has also been investigated. Results: A total of 198 eligible cis-unfit pts have been tested for PD-L1 and 71 (35.6%) have been found positive. Among enrolled patients (N=71), median age was 75 y, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS=2; 50 (70.4%) had CrCl <60 mL/min and 9 (12.7%) progressed within 6-mos from the end of neo/adj chemo. At the cut-off data (Feb 2, 2022), median follow up was 10.0 mos and 14 patients are still on treatment. The median OS was 10.0 mos (95% CI, 5.5-14.5), and 43.0% of patients were alive at 1-year. The ORR for all patients was 24.0%; complete response, 8.5% (n=6); partial response, 15.5% (n=11). Clinical benefit was 43.6% (n=31). Median PFS was 2.0 mos (95% CI, 1.7-2.3). Among the 17 pts who had tumour response 13 had DOR > 1y and 5 > 2y. A total of 67 patients have been evaluated for CPS and among these 56 (83.6%) have been classified as high expression. The median OS was 11.0 mos (95%CI, 0.1 – 22.9) for those with high CPS and 7.0 mos (95%CI 2.8 – 11.2) for low CPS (p=0.13). The median PFS was 2.0 mos for both high and low CPS (p=0.34). Five (7.0%) grade 3 ave-related adverse events, and no treatment-related death were reported. Conclusions: Ave is active and safe in pts with cis-unfit, PD-L1+ve aUC and poor baseline characteristics