Product and content personalization is now ubiquitous in e-commerce. There are typically not enough available transactional data for this task. As such, companies today seek to use a variety of ...information on the interactions between a product and a customer to drive personalization decisions. We formalize this problem as one of recovering a large-scale matrix with side information in the form of additional matrices of conforming dimension. Viewing the matrix we seek to recover and the side information we have as slices of a tensor, we consider the problem of
slice
recovery
, which is to recover specific slices of “simple” tensors from noisy observations of the entire tensor. We propose a definition of simplicity that on the one hand elegantly generalizes a standard generative model for our motivating problem and on the other hand subsumes low-rank tensors for a variety of existing definitions of tensor rank. We provide an efficient algorithm for slice recovery that is practical for massive data sets and provides a significant performance improvement over state-of-the-art incumbent approaches to tensor recovery. Furthermore, we establish near-optimal recovery guarantees that, in an important regime, represent an order improvement over the best available results for this problem. Experiments on data from a music streaming service demonstrate the performance and scalability of our algorithm.
The e-companion is available at
https://doi.org/10.1287/mnsc.2018.3092
.
This paper was accepted by Noah Gans, stochastic models and simulation.
The external incentives model (EIM) proved highly compelling in explaining Europeanization and rule adoption in countries from Central, Eastern and Southeast Europe. Building on the EIM, the present ...article seeks to contribute along three key objectives. First, it proposes to re‐evaluate the EIM for the Eastern European Neighbourhood Policy (ENP) region: Armenia, Azerbaijan, Georgia, Moldova and Ukraine. Second, the paper introduces a conceptual distinction between domestic transformation costs and regulatory costs. Third, it integrates and evaluates the EIM in a broader framework, incorporating domestic and alternative international conditions. The paper combines theory‐guided case comparisons and panel data analysis, based on a dataset with evidence collected from the Eastern ENP countries. The study corroborates the EIM and finds that higher domestic transformation costs lead to lower levels of democratic development and a positive cost–benefit balance of transformation, on the other hand, tends to encourage democratic consolidation in the Eastern ENP region.
RET fusions in solid tumors Li, Andrew Y.; McCusker, Michael G.; Russo, Alessandro ...
Cancer treatment reviews,
December 2019, 2019-Dec, 2019-12-00, 20191201, Letnik:
81
Journal Article
Recenzirano
•RET fusions represent an emerging relatively small subgroup of solid tumors that exhibit selective sensitivity to RET inhibitors.•Multiple non-selective RET inhibitors showed some activity in ...RET-rearranged NSCLC, albeit at lesser extent seen in other oncogene-addicted subgroups.•LOXO-292 and BLU-667 are novel RET inhibitors that provide a more selective blockage of the pathway, with a promising clinical activity in early clinical trials.•If these agents keep their promises, RET rearrangements could represent a novel tumor agnostic predictive biomarker for RET inhibition.
The RET proto-oncogene has been well-studied. RET is involved in many different physiological and developmental functions. When altered, RET mutations influence disease in a variety of organ systems from Hirschsprung’s disease and multiple endocrine neoplasia 2 (MEN2) to papillary thyroid carcinoma (PTC) and non-small cell lung cancer (NSCLC). Changes in RET expression have been discovered in 30–70% of invasive breast cancers and 50–60% of pancreatic ductal adenocarcinomas in addition to colorectal adenocarcinoma, melanoma, small cell lung cancer, neuroblastoma, and small intestine neuroendocrine tumors. RET mutations have been associated with tumor proliferation, invasion, and migration. RET fusions or rearrangements are somatic juxtapositions of 5′ sequences from other genes with 3′ RET sequences encoding tyrosine kinase. RET rearrangements occur in approximately 2.5–73% of sporadic PTC and 1–3% of NSCLC patients. The most common RET fusions are CDCC6-RET and NCOA4-RET in PTC and KIF5B-RET in NSCLC. Tyrosine kinase inhibitors are drugs that target kinases such as RET in RET-driven (RET-mutation or RET-fusion-positive) disease. Multikinase inhibitors (MKI) target various kinases and other receptors. Several MKIs are FDA-approved for cancer therapy (sunitinib, sorafenib, vandetanib, cabozantinib, regorafenib, ponatinib, lenvatinib, alectinib) and non-oncologic disease (nintedanib). Selective RET inhibitor drugs LOXO-292 (selpercatinib) and BLU-667 (pralsetinib) are also undergoing phase I/II and I clinical trials, respectively, with preliminary results demonstrating partial response and low incidence of serious adverse events. RET fusions provide a viable therapeutic target for oncologic treatment, and further study is warranted into the prevalence and pathogenesis of RET fusions as well as development of current and new tyrosine kinase inhibitors.
Abstract
Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics. It has been challenging to assess mRNA packaging characteristics in LNPs, including payload ...distribution and capacity, which are critical to understanding structure-property-function relationships for further carrier development. Here, we report a method based on the multi-laser cylindrical illumination confocal spectroscopy (CICS) technique to examine mRNA and lipid contents in LNP formulations at the single-nanoparticle level. By differentiating unencapsulated mRNAs, empty LNPs and mRNA-loaded LNPs via coincidence analysis of fluorescent tags on different LNP components, and quantitatively resolving single-mRNA fluorescence, we reveal that a commonly referenced benchmark formulation using DLin-MC3 as the ionizable lipid contains mostly 2 mRNAs per loaded LNP with a presence of 40%–80% empty LNPs depending on the assembly conditions. Systematic analysis of different formulations with control variables reveals a kinetically controlled assembly mechanism that governs the payload distribution and capacity in LNPs. These results form the foundation for a holistic understanding of the molecular assembly of mRNA LNPs.
Background & Aim
Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced ...fibrosis in a large national population sample is not well understood.
Methods
Cross‐sectional data from the National Health and Nutrition Examination Survey 1999‐2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB‐4 score.
Results
Of the 6738 participants (mean age 46.3 years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20‐39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32‐4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13‐3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high‐density lipoprotein cholesterol (P for trend <.05 respectively).
Conclusions
In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors.
See Article on Page 1730
Abstract Objective Stress may promote ovarian cancer progression through mechanisms including autonomic nervous system mediators such as norepinephrine and epinephrine. Beta blockers, used to treat ...hypertension, block production of these adrenergic hormones, and have been associated with prolonged survival in several malignancies. We sought to determine the association between beta blocker use and epithelial ovarian cancer (EOC) disease progression and survival. Methods We performed an institutional retrospective review of patients with EOC treated between 1996 and 2006. Patients underwent cytoreductive surgery followed by platinum-based chemotherapy. Women were considered beta blocker users if these medications were documented on at least two records more than 6 months apart. Statistical tests included Fisher's exact, Kaplan–Meier, and Cox regression analyses. Results 248 met inclusion criteria. 68 patients used antihypertensives, and 23 used beta blockers. Median progression-free survival for beta blocker users was 27 months, compared with 17 months for non-users ( p = 0.05). Similarly, overall disease-specific survival was longer for beta blocker users (56 months) compared with non-users (48 months, p = 0.02, hazard ratio = 0.56). Multivariate analysis identified beta blocker use as an independent positive prognostic factor, after controlling for age, stage, grade, and cytoreduction status ( p = 0.03). Overall survival remained longer for beta blocker users (56 months) when compared with hypertensive patients on other medications (34 months) and patients without hypertension (51 months) ( p = 0.007). Conclusions In this cohort of patients with EOC, beta blocker use was associated with a 54% reduced chance of death compared with that of non-users.
Ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete Borrelia turicatae and African swine fever virus. Historic ...collections of O. turicata have been recorded from Latin America to the southern United States. However, the geographic distribution of this vector is poorly understood in relation to environmental variables, their hosts, and consequently the pathogens they transmit.
Localities of O. turicata were generated by performing literature searches, evaluating records from the United States National Tick Collection and the Symbiota Collections of Arthropods Network, and by conducting field studies. Maximum entropy species distribution modeling (Maxent) was used to predict the current distribution of O. turicata. Vertebrate host diversity and GIS analyses of their distributions were used to ascertain the area of shared occupancy of both the hosts and vector.
Our results predicted previously unrecognized regions of the United States with habitat that may maintain O. turicata and could guide future surveillance efforts for a tick capable of transmitting high-consequence pathogens to human and animal populations.
The Boreas dataset was collected by driving a repeated route over the course of 1 year, resulting in stark seasonal variations and adverse weather conditions such as rain and falling snow. In total, ...the Boreas dataset includes over 350 km of driving data featuring a 128-channel Velodyne Alpha-Prime lidar, a 360° Navtech CIR304-H scanning radar, a 5MP FLIR Blackfly S camera, and centimetre-accurate post-processed ground truth poses. Our dataset will support live leaderboards for odometry, metric localization, and 3D object detection. The dataset and development kit are available at boreas.utias.utoronto.ca.
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