Developing robust bridge health monitoring (BHM) frameworks based on the vehicle-mounted sensing, or so-called indirect structural health monitoring (SHM) or Drive-by Bridge Inspection is currently a ...rapidly growing research area. The goal is to monitor any change in the structural integrity of a bridge using the vibration responses measured from sensors installed on a vehicle passing over the bridge. To this aim, we present a novel data-driven approach by integrating a nonlinear dimensionality-reduction technique using Uniform Manifold Approximation and Projection (UMAP) together with a non-parametric clustering technique using Hierarchical Density-Based Spatial Clustering of Applications with Noise (HDBSCAN). Ultimately, through the combined use of UMAP and HDBSCAN, it is demonstrated that such methods align perfectly well with the problems and restrictions present when analyzing drive-by bridge inspection data. That is, in the drive-by bridge inspection context data sets may have low cardinality, and the individual clusters may have different sizes and densities and do not need to have a spherical shape. Furthermore, new clusters may emerge over time as new damage cases evolve. The pairing of UMAP and HDBSCAN will be shown to assist in these issues in a principled manner. For the validation, we first make use of the theoretical formulation of the vehicle-bridge interaction system and conduct a finite element simulation of this system to obtain the moving vehicle response once traveling over five different bridge states. Further, a simply supported bridge model in the laboratory is considered for the experimental validation. The structure of the bridge model is gradually changed by adding multiple stiffener plates, and by gradually increasing a concentrated mass at mid-span. The proposed method is then applied to identify changes that occur in the laboratory bridge model. The experimental results for damage characterization demonstrate that various bridge states can successfully be separated from one another. The contributions of the work are three-fold; (1) First, a novel feature extraction and classification framework based on the combined use of UMAP and HDBSCAN is developed and validated. (2) Second, this paper demonstrates one of the early successful attempts of drive-by bridge inspection for monitoring the progressive change in the structure of a bridge based on the extensive numerical and experimental investigations. (3) Finally, the research presented in this work can open up new opportunities for condition monitoring of bridge network.
•A novel feature extraction and classification framework is developed and validated.•Superior performance of the method by combined use of UMAP and HDBSCAN is presented.•One of the early successful attempts of drive-by bridge inspection is demonstrated.
Oncogenic gene fusions are hybrid genes that result from structural DNA rearrangements, leading to deregulated activity. Fusions involving the neuregulin-1 gene (NRG1) result in ErbB-mediated pathway ...activation and therefore present a rational candidate for targeted treatment. The most frequently reported NRG1 fusion is CD74-NRG1, which most commonly occurs in patients with invasive mucinous adenocarcinomas (IMAs) of the lung, although several other NRG1 fusion partners have been identified in patients with lung cancer, including ATP1B1, SDC4, and RBPMS. NRG1 fusions are also present in patients with other solid tumors, such as pancreatic ductal adenocarcinoma. In general, NRG1 fusions are rare across different types of cancer, with a reported incidence of <1%, with the notable exception of IMA, which represents ≈2%–10% of lung adenocarcinomas and has a reported incidence of ≈10%–30% for NRG1 fusions. A substantial proportion (≈20%) of NRG1 fusion-positive non-small-cell lung cancer cases are nonmucinous adenocarcinomas. ErbB-targeted treatments, such as afatinib, a pan-ErbB tyrosine kinase inhibitor, are potential therapeutic strategies to address unmet treatment needs in patients harboring NRG1 fusions.
•NRG1 fusions result in ErbB-mediated pathway activation and present a rational therapeutic target.•ErbB-targeted treatments, such as afatinib, can be effective therapeutic options in tumors harboring NRG1 fusions.•The incidence of NRG1 fusion-driven tumors is low, occurring in <1% of cancers, but is highest (≈10-30%) in invasive mucinous adenocarcinoma.
The development of a fully automated system identifier without the need for human intervention, is a key step for real-time vibration-based Structural Health Monitoring (SHM). In this paper a novel ...approach based on the Dirichlet Process Gaussian Mixture Model (DP-GMM) is developed in order to analyze the stabilization diagram. The aim is to separate the true physical modes from the mathematically spurious modes in a fully automated manner, whilst eliminating the need for any manually specified parameters or thresholds. The parametric Covariance Driven Stochastic Subspace Identification (SSI-Cov) is adopted to estimate the modal parameters, and consequently establish the initial stabilization diagram. From there, the use of a two-stage algorithm involving a DP-GMM is proposed to non-parametrically perform an automated cleaning of the stabilization diagram. The contributions of the paper are five-fold: (1) A probabilistic approach based on a DP-GMM is proposed to analyze the stabilization diagram. To the best knowledge of the authors, this study presents one of the first attempts of DP-GMM for full automation of Operational Modal Analysis (OMA). The method is validated using the field test data from a large-scale operating cable-stayed bridge, which has two closely-spaced modes around 3 Hz. Not only are these two complicated scenarios consistently identified, but the performance of the method with respect to the problem of missing modes is compared against a reference method based on the conventional multi-stage clustering technique used in OMA, wherein superior performance of the proposed method is demonstrated. (2) The method does not require specification of any threshold or parameter at any stage of the algorithm for cleaning the stabilization diagram, making the approach a potential for robust and fully automated modal identification. (3) Compared to many conventional multi-stage clustering techniques, the proposed approach is computationally efficient as intelligent updates are made to the model using multiple linear algebra properties. (4) New feature vectors are developed which are justified using a combination of mathematical rigor, visual understanding, and engineering intuition. (5) Due to the probabilistic nature of the method, the identification results are accompanied with uncertainty bounds. Several mathematical proofs are presented to explain the observed behavior of the uncertainty bounds.
For more than a decade, there has been no improvement in outcomes for patients with unresectable locally advanced (la) non-small-cell lung cancer (nsclc). The standard treatment in that setting is ...definitive concurrent chemotherapy and radiation (ccrt). Although the intent of treatment is curative, most patients rapidly progress, and their prognosis is poor, with a 5-year overall survival (os) rate in the 15%-25% range. Those patients therefore represent a critical unmet need, warranting expedited approval of, and access to, new treatments that can improve outcomes. The pacific trial, which evaluated durvalumab consolidation therapy after ccrt in unresectable la nsclc, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (pfs) and a significant improvement in os. Durvalumab thus fills a critical unmet need in the setting of unresectable la nsclc and provides a new option for patients treated with curative intent. Here, we review the treatment of unresectable la nsclc, with a focus on the effect of the clinical data for durvalumab.
The advent of personalized therapy for non-small-cell lung carcinoma (nsclc) has improved patient outcomes. Selection of appropriate targeted therapy for patients with nsclc now involves testing for ...multiple biomarkers, including
.
mutation status is required to optimally treat patients with nsclc, and thus timely and accurate biomarker testing is necessary. However, in Canada, there are currently no standardized processes or methods in place to ensure consistent testing implementation. That lack creates challenges in ensuring that all appropriate biomarkers are tested for each patient and that the medical oncologist receives the results for making informed treatment decisions in a timely way. An expert multidisciplinary working group was convened to create consensus recommendations about biomarker testing in advanced nsclc in Canada, with a primary focus on
testing. Recognizing that there are biomarkers beyond
that require timely identification, the expert multidisciplinary working group considered
testing in the broader context of integration into complex lung biomarker testing. Primarily, the panel of experts recommends that all patients with nonsquamous nsclc, regardless of stage, should undergo comprehensive reflex biomarker testing at diagnosis with targeted next-generation sequencing. The panel also considered the
testing algorithm and the challenges associated with the pre-analytic, analytic, and post-analytic elements of testing. Strategies for funding testing by reducing silos of single biomarker testing for
and for optimally implementing the recommendations presented here and educating oncology professionals about them are also discussed.
Evaluate inter-country variability in the reimbursement of publically funded cancer drugs, and identify factors such as cost containment measures that may contribute to variability.
As of February ...28, 2010, licensed indications for 10 cancer drugs (bevacizumab, bortezomib, cetuximab, erlotinib, imatinib, pemetrexed, rituximab, sorafenib, sunitinib, and trastuzumab) were obtained from the drug registries of 6 licensing authorities corresponding to 13 countries or regions: Australia, Canada (Ontario), England, Finland, France, Italy, Germany, Japan, New Zealand, the Netherlands, Scotland, Sweden, and the United States (Medicare Parts B and D). Number of licensed indications reimbursed by public payers and the use of cost containment measures were obtained by survey of health authorities involved in reimbursement and through public documents.
The 48 identified licensed indications varied between agencies (range: 36-44 indications). Finland, France, Germany, Sweden, and the United States reimbursed the highest percentage of indications (range: 90%-100%). Canada (54%), Australia (46%), Scotland (40%), England (38%), and New Zealand (25%) reimbursed the least. All 5 countries with the lowest rate of reimbursement incorporated a cost-effectiveness analysis into reimbursement decisions and rejected submissions for reimbursement mainly because of lack of cost effectiveness; in New Zealand, lack of cost effectiveness was the second leading cause of rejection after excessive cost. In 9 countries, risk-sharing agreements were used to contain costs. Indications initially not recommended for reimbursement (9 in Australia, 5 in Canada, and 3 in England, New Zealand, and Scotland) were subsequently approved with risk-sharing agreements or special pricing arrangements.
Reimbursement of publically funded cancer drugs varies globally. The cause is multifactorial.
An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal ...cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4-ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc.
Multiple clinical trials for the treatment of advanced
mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important ...clinical questions have been raised:■ What is the optimal first-line treatment for patients with
mutated nsclc?■ What is preferred first-line treatment for patients with brain metastasis?■ What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)?■ What is the preferred treatment after osimertinib?■ What evidence do we have for treating patients whose tumours harbour uncommon
mutations?
A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced
mutated nsclc.
The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common
mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon
mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed.
This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of
mutated nsclc.
Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and ...pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment.
An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions.
Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified.
In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged.
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