Understanding the problem of bridge and tunnel strikes caused by over-height vehicles

A bridge or tunnel strike is an incident in which a vehicle that is taller than the clearance underneath the structure (over-height), typically a lorry or double-decker bus, collides with the structure causing damage. This can lead to injuries, fatalities and/or, in worst case scenario, train derailments. Bridge and tunnel strikes are costly and expensive. The annual maintenance costs to repair and service the structure have been reported to range in the tens-to-hundreds of thousands (£) while the average cost per strike ranges between £5,000 to £25,000. In this paper, we present a comprehensive synthesis of the nature and scope of the problem of bridge and tunnel strikes, followed by the current state of practice and current state of research. Bridge and tunnel strikes still occur with high frequency, and prevention systems (passive, sacrificial and active) available on the market are often too expensive. Bridge-owners are seeking an affordable yet reliable system that is cheap enough for widespread installation without compromising the accuracy and performance of such a system.This material is based upon work supported by Transport for London.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.trpro.2016.05.48

Motion Trajectories of Over-Height Vehicles for Warning Drivers

Collision of over-height vehicles with low bridges and tunnels occur with high frequency in the UK as many structures were built at a time when there was less moving traffic on the roadway. These older bridges are now considered at risk of vehicular strikes due to its low clearance height (less than 16 feet 6 inches or 5.03 metres). While previous methods have used vision-based systems to address the over-height warning problem, such methods are sensitive to wind. In this paper, we proposed an extension of the work done to minimise false detections due to wind by using a constraint-based method to track motion trajectories to improve the overall performance of the system. The dataset consists of 102 over-height vehicles recorded at 25 fps. The paper compares feature detectors to optimally track vehicle trajectories and analyses its motion to accurately classify positive detections. The final validation yields a performance of 94.5% recall and 91.1% precision.Career Integration Grants (CIG) - Marie Curie Action

Vision-Based Over-Height Vehicle Detection for Warning Drivers

Many older bridges and tunnels were constructed using standards by now many decades out-of-date, at a time when trucks and other large vehicles were smaller. A bridge or tunnel strike is an incidence in which a vehicle, typically a lorry (truck) or double-decker bus, tries to pass under a bridge or tunnel that is lower than its height, subsequently colliding with the structure. These strikes lead to an increased cost of bridge repairs, clogged up roadways and increased potential for catastrophic events: hazardous spillage and/or total collapse. Today, Network Rail reports on average a strike every 4.5 hours. There are a number of reasons why strikes occur, and why drivers of heavy goods vehicles sometimes fail to recognise the warning signs, consequently striking the bridge or tunnel. At first glance, it may seem like the problem is a fairly easy one to solve; however, no matter how well planned the road system, human error is an ever-present risk. The research proposes to address the problem of bridge and tunnel strike prevention and management. The intent of the research is to develop an affordable, reliable and robust early warning over-height detection system bridge-owners can implement at locations with high strike occurrences. The research aims to test and validate a novel vision-based system using a single camera to accurately detect over-height vehicles using a set of optimised parameters. The system uses a camera installed at the offending height, which acts as an “over-height plane” formed by the averages of the maximum allowable heights across all lanes in a given traffic direction. Any vehicle exceeding this plane is analysed within a region of interest using a trigger-based approach for accurate detection and driver warning. If the vehicle is deemed to be over-height, a warning is issued to the driver. As a result, prolonging life expectancy of structures while decreasing the cost of repairs, maintenance and inspections.Transport for London Cambridge Centre for Smart Infrastructure Cambridge Overseas Trust Marie Curie Staff Exchang

Iodine deficiency in pregnant women in the ACT

In response to growing concern of an iodine deficiency emergence in Australia, this study was conducted to document the iodine status of pregnant women in the ACT. One hundred women presenting to the antenatal clinic at The Canberra Hospital answered a brief dietary questionnaire and provided a spot urine sample for the measurement of urine iodine excretion. The results revealed that the majority of women were consuming a diet low in iodine, confirmed by suboptimal concentrations of iodine in their urine

Comparison of circulating tumour dna and extracellular vesicle dna by low-pass whole-genome sequencing reveals molecular drivers of disease in a breast cancer patient

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both ctDNA and EV DNA from a patient with breast cancer. Of the 52 CNVs identified in tumour DNA, 36 (69%) were detected in at least one ctDNA sample and 13 (25%) in at least one EV DNA sample. The number of detectable variants in ctDNA and EV DNA increased over the natural history of the patient’s disease, which was associated with progression to cerebral metastases. This case study demonstrates that, while CNVs are detectable in patient EV DNA, ctDNA has greater sensitivity than EV DNA for serial monitoring of breast cancer

Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

© 2021, The Author(s). Low-coverage whole-genome sequencing (LC-WGS) can provide insight into oncogenic molecular changes. Serum extracellular vesicles (EV) represent a novel liquid biopsy source of tumoral DNA. This study compared copy number alteration (CNA) profiles generated from LC-WGS of formalin-fixed paraffin-embedded (FFPE) tumoral DNA and EV-DNA obtained from cancer patients. Patients with squamous cell carcinoma of the base of tongue (n = 3) and cutaneous squamous cell carcinoma (n = 2) were included. LC-WGS (0.5-1X coverage) was performed on FFPE-DNA and serum EV-DNA. Similarity between CNA profiles was analysed using QDNAseq. FFPE samples had a mean CNA of 31 (range 17–50) over 1.9 × 109 (range 1.0–2.6 × 109) bp in length, and EV samples had a mean CNA value of 17 (range 7–19) over 7.6 × 108 (range 2.9–15 × 108) bp in length. A mean of 8 (range 0–21) CNA over 5.9 × 108 (range 1.6–14 × 108) bp in length was found to overlap between EV and FFPE-derived samples per patient. Although the mean correlation efficient between samples was r = 0.34 (range − .08 to 0.99), this was not statistically significant (p \u3e 0.05). Regions of highest deletion and duplication in FFPE samples were not well reflected in the EV-DNA. Selected CNA regions in EV-associated DNA were reflective of the primary tumor, however appreciation of global CNA and areas of most significant change was lost. The utility of LC-WGS of EV-derived DNA is likely limited to molecular alterations of known interest

ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disease progression

Background: Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived microglia-like cells that are capable of expressing molecular markers, and functional characteristics similar to in vivo human brain microglia. Methods: In this study, we have established monocyte-derived microglia-like cells from 30 sporadic patients with ALS, including 15 patients with slow disease progression, 6 with intermediate progression, and 9 with rapid progression, together with 20 non-affected healthy controls. Results: We demonstrate that patient monocyte-derived microglia-like cells recapitulate canonical pathological features of ALS including non-phosphorylated and phosphorylated-TDP-43-positive inclusions. Moreover, ALS microglia-like cells showed significantly impaired phagocytosis, altered cytokine profiles, and abnormal morphologies consistent with a neuroinflammatory phenotype. Interestingly, all ALS microglia-like cells showed abnormal phagocytosis consistent with the progression of the disease. In-depth analysis of ALS microglia-like cells from the rapid disease progression cohort revealed significantly altered cell-specific variation in phagocytic function. In addition, DNA damage and NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activity were also elevated in ALS patient monocyte-derived microglia-like cells, indicating a potential new pathway involved in driving disease progression. Conclusions: Taken together, our work demonstrates that the monocyte-derived microglia-like cell model recapitulates disease-specific hallmarks and characteristics that substantiate patient heterogeneity associated with disease subgroups. Thus, monocyte-derived microglia-like cells are highly applicable to monitor disease progression and can be applied as a functional readout in clinical trials for anti-neuroinflammatory agents, providing a basis for personalised treatment for patients with ALS

Evaluation of provider documentation of medication management in a Patient-Centered Medical Home (PCMH)

Purpose: The National Committee for Quality Assurance (NCQA) has standards for recognizing Patient-Centered Medical Homes (PCMH) including one for medication management. Study objectives were to identify if and how providers within a PCMH recognized under the 2008 guidelines were documenting components of medication management to meet NCQA’s 2011 requirements including: 1) providing information about new prescriptions to >80% of patients; 2) assessing understanding of medications for >50% of patients; and 3) assessing response and barriers to medication adherence for >50% of patients. Methods: Physician and pharmacist-led patient visits from a family medicine office, from February 1 to August 1, 2012 were assessed. Patients over 18 years old taking at least one medication were included. A retrospective chart review was performed to assess documented components of medication management. Descriptive statistics were used to analyze data. Results: A systematic sampling of 450 physician-led and 195 pharmacist-led patient visits, demonstrated providers did not meet documentation goals for providing patients information on new prescriptions (65% pharmacist, 24% physician, 36% of total provider notes) or for assessment of patients’ understanding of medications (9% pharmacist 12% physician, 11% of total provider notes). Individually each type of provider did not meet the goal of assessing patient response and barriers to adherence to medication, but with combined intervention by the pharmacists and the physicians, the site was able to surpass NCQA’s percentage goal (57% and 58%). Conclusions: No components of medication management are well documented. Using the electronic medical record, pharmacists may be able to develop documentation tools and assist sites to meet NCQA’s goals for medication management

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = \u3c 0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation. © 2020, The Author(s)

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = \u3c 0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation. © 2020, The Author(s)