Recently, domain adaptation has received extensive attention for solving intelligent fault diagnosis problems. It aims to reduce the distribution discrepancy between the source domain and target ...domain through learning domain-invariant features. However, most existing domain-adaptation methods mainly focus on global domain adaptation and overlook subdomain adaptation, which results in the loss of fine-grained information and discriminative features. To address this problem, in this paper, a deep adversarial subdomain adaptation network is proposed. This network aligns the relevant distributions of subdomains by minimizing the local maximum mean discrepancy loss of the same categories in the source domain and target domain. Under the constraints of global domain adaptation and subdomain adaptation, the distribution discrepancy is reduced from the domain and category levels. Four transfer tasks under different machine rotating speeds and six transfer tasks on different but related machines were used to evaluate the effectiveness of the proposed method. The results demonstrated the robustness and superiority of the proposed method over five other methods.
Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are noncoding RNAs with important roles in gene regulation. They have recently been investigated as ...novel classes of therapeutic agents for the treatment of a wide range of disorders including cancers and infections. Clinical trials of siRNA- and miRNA-based drugs have already been initiated. siRNAs and miRNAs share many similarities, both are short duplex RNA molecules that exert gene silencing effects at the post-transcriptional level by targeting messenger RNA (mRNA), yet their mechanisms of action and clinical applications are distinct. The major difference between siRNAs and miRNAs is that the former are highly specific with only one mRNA target, whereas the latter have multiple targets. The therapeutic approaches of siRNAs and miRNAs are therefore very different. Hence, this review provides a comparison between therapeutic siRNAs and miRNAs in terms of their mechanisms of action, physicochemical properties, delivery, and clinical applications. Moreover, the challenges in developing both classes of RNA as therapeutics are also discussed.
Ceritinib is 20 times as potent as crizotinib at inhibiting anaplastic lymphoma kinase (ALK) in vitro. In patients, ceritinib produced antitumor responses in 56% of those who had resistance to ...crizotinib.
Genetic alterations in the anaplastic lymphoma kinase gene (
ALK
) are implicated in the pathogenesis of several human cancers.
1
ALK can be aberrantly activated by mutation, gene amplification, or chromosomal rearrangement, leading to the expression of a potent oncogenic driver. In non–small-cell lung cancer (NSCLC),
ALK
rearrangement occurs in approximately 5% of cases.
2
–
8
ALK
-rearranged tumors depend on ALK for growth and survival and show marked sensitivity to ALK inhibitors such as crizotinib. Among patients with advanced,
ALK
-rearranged NSCLC, crizotinib has been associated with response rates of approximately 60% across multiple studies and a median progression-free survival . . .
Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy ...of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (
Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 27.7%) v 82 of 162 50.6%; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 3.8% v four of 162 2.5% patients), abdominal pain (three 2.3% v two 1.2% patients), anemia (zero v four 2.5% patients), and radiation hepatitis (two 1.5% v zero 0% patients). Fewer patients in the RE group (27 of 130 20.8%) than in the sorafenib group (57 of 162 35.2%) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.
Anomaly Detection and Fault Prognosis for Bearings Xiaohang Jin; Yi Sun; Zijun Que ...
IEEE transactions on instrumentation and measurement,
2016-Sept., 2016-9-00, 20160901, Volume:
65, Issue:
9
Journal Article
Peer reviewed
In this paper, a new bearing anomaly detection and fault prognosis method is proposed. The method detects bearing anomalies and then predicts its remaining useful life (RUL). To achieve these two ...goals, an autoregressive model, which is used to filter out fault-unrelated signals, is derived according to healthy bearing vibrational signals. A health index is developed to indicate bearing health conditions. Anomalies of bearings are detected by choosing an appropriate threshold with the aid of a Box-Cox transformation. A nonlinear model is built to track the bearings' degradation process and an extended Kalman filter is designed to model adaptation and RUL prediction. Finally, PRONOSTIA bearing data are used to demonstrate the effectiveness of the proposed method.
High prevalence of anxiety symptoms has been reported globally in the university students. Cognitive behavioral therapy (CBT) is the recognized treatment for anxiety and is traditionally conducted ...face-to-face (f-CBT). The efficacy of internet-based CBT (i-CBT) for anxiety has been extensively studied, yet evidence on its cost-effectiveness is scarce. We aimed to evaluate the cost-effectiveness of guided low-intensity i-CBT for university students with mild anxiety symptoms from the societal perspective of Hong Kong.
A 5-year Markov model was designed to compare outcomes of guided i-CBT and f-CBT in a hypothetical cohort of university students with mild anxiety symptoms. Model inputs of cost and healthcare resources associated with anxiety were retrospectively collected from a cohort of university students with anxiety symptoms. Clinical and utility model inputs were retrieved from published literature. Model outcome measures were anxiety-related total cost (including direct medical and indirect costs) and quality-adjusted life-year (QALY). Sensitivity analyses were performed to examine the robustness of base-case results.
In base-case analysis, i-CBT gained higher QALYs (2.9956 versus 2.9917) at lower total cost (US$6,101 versus US$6,246) than f-CBT. In one-way sensitivity analysis, the QALY gained by i-CBT was sensitive to the relative patient acceptance and adherence to CBT. In probabilistic sensitivity analysis, i-CBT was cost-effective in 90.9% of the time at the willingness-to-pay threshold of 138,210 per QALY (3× GDP per capita in Hong Kong). The probability of i-CBT to be cost-effective was 99.9% at a willingness-to-pay threshold of zero.
Guided i-CBT appears to be cost-saving and effective for management of university students with mild symptoms of anxiety from the societal perspective of Hong Kong. The cost-effectiveness of i-CBT is highly subject to the individual acceptance and adherence of CBT delivered by the internet platform.
Bearings are critical components in induction motors and brushless direct current motors. Bearing failure is the most common failure mode in these motors. By implementing health monitoring and fault ...diagnosis of bearings, unscheduled maintenance and economic losses caused by bearing failures can be avoided. This paper introduces trace ratio linear discriminant analysis (TR-LDA) to deal with high-dimensional non-Gaussian fault data for dimension reduction and fault classification. Motor bearing data with single-point faults and generalized-roughness faults are used to validate the effectiveness of the proposed method for fault diagnosis. Comparisons with other conventional methods, such as principal component analysis, local preserving projection, canonical correction analysis, maximum margin criterion, LDA, and marginal Fisher analysis, show the superiority of TR-LDA in fault diagnosis.
Exactly Robust Kernel Principal Component Analysis Fan, Jicong; Chow, Tommy W. S.
IEEE transaction on neural networks and learning systems,
2020-March, 2020-Mar, 2020-3-00, 20200301, Volume:
31, Issue:
3
Journal Article
Open access
Robust principal component analysis (RPCA) can recover low-rank matrices when they are corrupted by sparse noises. In practice, many matrices are, however, of high rank and, hence, cannot be ...recovered by RPCA. We propose a novel method called robust kernel principal component analysis (RKPCA) to decompose a partially corrupted matrix as a sparse matrix plus a high- or full-rank matrix with low latent dimensionality. RKPCA can be applied to many problems such as noise removal and subspace clustering and is still the only unsupervised nonlinear method robust to sparse noises. Our theoretical analysis shows that, with high probability, RKPCA can provide high recovery accuracy. The optimization of RKPCA involves nonconvex and indifferentiable problems. We propose two nonconvex optimization algorithms for RKPCA. They are alternating direction method of multipliers with backtracking line search and proximal linearized minimization with adaptive step size (AdSS). Comparative studies in noise removal and robust subspace clustering corroborate the effectiveness and the superiority of RKPCA.
Activation of the receptor for advanced glycation end products (RAGE, also known as AGE-specific receptor AGER) has been implicated in the development of diabetic vascular complications. Blockade of ...RAGE using a soluble form of the receptor (sRAGE) suppressed vascular hyperpermeability and atherosclerosis in animal models. Since little is known about the regulation of endogenous sRAGE levels, we determined whether serum sRAGE is influenced by circulating AGEs and the severity of nephropathy in type 2 diabetic patients.
We recruited 150 healthy control and 318 diabetic subjects. Diabetic subjects were subdivided into those with proteinuria, microalbuminuria or normoalbuminuria. Serum sRAGE was assayed by ELISA and serum AGEs by competitive ELISA using a polyclonal rabbit antiserum raised against AGE-RNase.
Diabetic subjects had higher sRAGE (1,029.5 pg/ml 766.1-1,423.0 interquartile range vs 1,002.6 726.5-1,345.3, p<0.05) and AGEs (4.07+/-1.13, SD, unit/ml vs 3.39+/-1.05, p<0.01) than controls. Proteinuric subjects had the highest sRAGE levels and there was a significant trend between the severity of nephropathy and sRAGE (p=0.01). In diabetic subjects, serum log(sRAGE) correlated with AGEs (r=0.27, p<0.001), log(plasma creatinine) (r=0.31, p<0.001), log(urine AER) (r=0.24, p<0.01) and log(triglycerides) (r=0.15, p<0.01). On stepwise linear regression analysis, AGEs and creatinine levels were the main independent determinants of sRAGE concentration.
Serum sRAGE levels and circulating AGEs are associated with the severity of nephropathy in type 2 diabetic patients. Prospective studies are required to determine whether endogenous sRAGE potentially influences the development of diabetic vascular complications.
Summary Background ALK -rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often ...with progression in the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood–brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease. We aimed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK -rearranged NSCLC. Methods ASCEND-1 was an open-label, phase 1 trial that recruited patients from 20 academic hospitals or cancer centres in 11 countries in Europe, North America, and Asia-Pacific. Eligible patients were aged 18 years or older with ALK -rearranged locally advanced or metastatic cancer that had progressed despite standard therapy (or for which no effective standard therapy existed), who had at least one measurable lesion at baseline. The primary objective (to determine the maximum tolerated dose) has been reported previously. This updated analysis includes all patients with ALK -rearranged NSCLC given oral ceritinib at the recommended dose of 750 mg/day in the dose-escalation and expansion phases. Here we report the secondary outcomes of overall response, duration of response, and progression-free survival, analysed in all patients who received at least one 750 mg dose of ceritinib. Exploratory analyses included retrospective analysis of intracranial activity by independent neuroradiologists, in patients with untreated or locally treated neurologically stable brain metastases at baseline. Safety was assessed in all patients who received at least one dose of ceritinib. This study is no longer recruiting patients; however, treatment and follow-up are ongoing. This study is registered with ClinicalTrials.gov , number NCT01283516. Findings Between Jan 24, 2011, and July 31, 2013, 255 patients were enrolled and received at least one dose of ceritinib 750 mg/day, of whom 246 had ALK -rearranged NSCLC. At data cutoff (April 14, 2014), median follow-up was 11·1 months (IQR 6·7–15·2) and 147 (60%) patients had discontinued treatment, 98 (40%) as a result of disease progression. An overall response was reported in 60 (72% 95% CI 61–82) of 83 ALK inhibitor-naive patients and 92 (56% 49–64) of 163 ALK inhibitor-pretreated patients. Median duration of response was 17·0 months (95% CI 11·3–non-estimable NE) in ALK inhibitor-naive patients and 8·3 months (6·8–9·7) in ALK inhibitor-pretreated patients. Median progression-free survival was 18·4 months (95% CI 11·1–NE) in ALK inhibitor-naive patients and 6·9 months (5·6–8·7) in ALK inhibitor-pretreated patients. Of 94 patients with retrospectively confirmed brain metastases and at least one post-baseline MRI or CT tumour assessment, intracranial disease control was reported in 15 (79% 95% CI 54–94) of 19 ALK inhibitor-naive patients and in 49 (65% 54–76) of 75 ALK inhibitor-pretreated patients. Of these 94 patients, 11 had measurable brain lesions and no previous radiotherapy to the brain, six of whom achieved a partial intracranial response. Serious adverse events were recorded in 117 (48%) of 246 patients. The most common grade 3–4 laboratory abnormalities were increased alanine aminotransferase (73 30% patients) and increased aspartate aminotransferase (25 10%). The most common grade 3–4 non-laboratory adverse events were diarrhoea and nausea, both of which occurred in 15 (6%) patients. Two on-treatment deaths during the study were deemed to be related to study drug by the investigators, one due to interstitial lung disease and one as a result of multiorgan failure that occurred in the context of infection and ischaemic hepatitis. Interpretation The durable whole-body responses reported, together with the intracranial activity, support a clinical benefit for treatment with ceritinib in patients with ALK -rearranged NSCLC who have received crizotinib, or as an alternative to crizotinib. A confirmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK -rearranged NSCLC and brain or leptomeningeal metastases. Funding Novartis Pharmaceuticals Corporation.
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