The topic of multi-person pose estimation has been largely improved recently, especially with the development of convolutional neural network. However, there still exist a lot of challenging cases, such as occluded keypoints, invisible keypoints and complex background, which cannot be well addressed. In this paper, we present a novel network structure called Cascaded Pyramid Network (CPN) which targets to relieve the problem from these "hard" keypoints. More specifically, our algorithm includes two stages: Glob-alNet and RefineNet. GlobalNet is a feature pyramid network which can successfully localize the "simple" keypoints like eyes and hands but may fail to precisely recognize the occluded or invisible keypoints. Our RefineNet tries explicitly handling the "hard" keypoints by integrating all levels of feature representations from the Global-Net together with an online hard keypoint mining loss. In general, to address the multi-person pose estimation problem, a top-down pipeline is adopted to first generate a set of human bounding boxes based on a detector, followed by our CPN for keypoint localization in each human bounding box. Based on the proposed algorithm, we achieve stateof-art results on the COCO keypoint benchmark, with average precision at 73.0 on the COCO test-dev dataset and 72.1 on the COCO test-challenge dataset, which is a 19% relative improvement compared with 60.5 from the COCO 2016 keypoint challenge. Code 1 and the detection results are publicly available for further research.
We address covariance estimation in the sense of minimum mean-squared error (MMSE) for Gaussian samples. Specifically, we consider shrinkage methods which are suitable for high dimensional problems with a small number of samples (large p small n). First, we improve on the Ledoit-Wolf (LW) method by conditioning on a sufficient statistic. By the Rao-Blackwell theorem, this yields a new estimator called RBLW, whose mean-squared error dominates that of LW for Gaussian variables. Second, to further reduce the estimation error, we propose an iterative approach which approximates the clairvoyant shrinkage estimator. Convergence of this iterative method is established and a closed form expression for the limit is determined, which is referred to as the oracle approximating shrinkage (OAS) estimator. Both RBLW and OAS estimators have simple expressions and are easily implemented. Although the two methods are developed from different persepctives, their structure is identical up to specified constants. The RBLW estimator provably dominates the LW method. Numerical simulations demonstrate that the OAS approach can perform even better than RBLW, especially when n is much less than p. We also demonstrate the performance of these techniques in the context of adaptive beamforming.
Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment.
We present a unified, efficient and effective framework for point-cloud based 3D object detection. Our two-stage approach utilizes both voxel representation and raw point cloud data to exploit respective advantages. The first stage network, with voxel representation as input, only consists of light convolutional operations, producing a small number of high-quality initial predictions. Coordinate and indexed convolutional feature of each point in initial prediction are effectively fused with the attention mechanism, preserving both accurate localization and context information. The second stage works on interior points with their fused feature for further refining the prediction. Our method is evaluated on KITTI dataset, in terms of both 3D and Bird's Eye View (BEV) detection, and achieves state-of-the-arts with a 15FPS detection rate.
Purpose In early breast cancer (BC), five conventional biomarkers—estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, and Nottingham histologic grade (NHG)—are used to determine prognosis and treatment. We aimed to develop classifiers for these biomarkers that were based on tumor mRNA sequencing (RNA-seq), compare classification performance, and test whether such predictors could add value for risk stratification. Methods In total, 3,678 patients with BC were studied. For 405 tumors, a comprehensive multi-rater histopathologic evaluation was performed. Using RNA-seq data, single-gene classifiers and multigene classifiers (MGCs) were trained on consensus histopathology labels. Trained classifiers were tested on a prospective population-based series of 3,273 BCs that included a median follow-up of 52 months (Sweden Cancerome Analysis Network—Breast [SCAN-B], ClinicalTrials.gov identifier: NCT02306096), and results were evaluated by agreement statistics and Kaplan-Meier and Cox survival analyses. Results Pathologist concordance was high for ER, PgR, and HER2 (average κ, 0.920, 0.891, and 0.899, respectively) but moderate for Ki67 and NHG (average κ, 0.734 and 0.581). Concordance between RNA-seq classifiers and histopathology for the independent cohort of 3,273 was similar to interpathologist concordance. Patients with discordant classifications, predicted as hormone responsive by histopathology but non–hormone responsive by MGC, had significantly inferior overall survival compared with patients who had concordant results. This extended to patients who received no adjuvant therapy (hazard ratio [HR], 3.19; 95% CI, 1.19 to 8.57), or endocrine therapy alone (HR, 2.64; 95% CI, 1.55 to 4.51). For cases identified as hormone responsive by histopathology and who received endocrine therapy alone, the MGC hormone-responsive classifier remained significant after multivariable adjustment (HR, 2.45; 95% CI, 1.39 to 4.34). Conclusion Classification error rates for RNA-seq–based classifiers for the five key BC biomarkers generally were equivalent to conventional histopathology. However, RNA-seq classifiers provided added clinical value in particular for tumors determined by histopathology to be hormone responsive but by RNA-seq to be hormone insensitive.
BackgroundThe basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.MethodsOne hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor therapy was investigated in breast cancer cell lines and mouse xenograft models, respectively.ResultsSixty-four % of cases had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of estrogen receptor (ER)-negative tumors. PTEN-loss was significantly associated to stathmin and EGFR overexpression, positivity for the BLBC markers cytokeratin 5/14, and the BLBC molecular subtype by gene expression profiling, informing a potential therapeutic combination targeting these pathways in BLBC. Combination treatment of BLBC cell lines with the EGFR-inhibitor gefitinib plus the PI3K pathway inhibitor LY294002 was synergistic, and correspondingly, in an in vivo BLBC xenograft mouse model, gefitinib plus PI3K-inhibitor PWT-458 was more effective than either monotherapy and caused tumor regression.ConclusionsOur study emphasizes the importance of PI3K/PTEN pathway activity in ER-negative and basal-like breast cancer and supports the future clinical evaluation of combining EGFR and PI3K pathway inhibitors for the treatment of BLBC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2609-2) contains supplementary material, which is available to authorized users.
We address covariance estimation under mean-squared loss in the Gaussian setting. Specifically, we consider shrinkage methods which are suitable for high dimensional problems with small number of samples (large p small n). First, we improve on the LedoitWolf (LW) method by conditioning on a sufficient statistic via the Rao-Blackwell theorem, obtaining a new estimator RBLW whose mean-squared error dominates the LW under Gaussian model. Second, to further reduce the estimation error, we propose an iterative approach which approximates the clairvoyant shrinkage estimator. Convergence of this iterative method is proved and a closed form expression for the limit is determined, which is called the OAS estimator. Both of the proposed estimators have simple expressions and are easy to compute. Although the two methods are developed from different approaches, their structure is identical up to specific constants. The RBLW estimator provably dominates the LW method; and numerical simulations demonstrate that the OAS estimator performs even better, especially when n is much less than p.
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