On the difficulty of learning chaotic dynamics with RNNs

Recurrent neural networks (RNNs) are wide-spread machine learning tools for modeling sequential and time series data. They are notoriously hard to train because their loss gradients backpropagated in time tend to saturate or diverge during training. This is known as the exploding and vanishing gradient problem. Previous solutions to this issue either built on rather complicated, purpose-engineered architectures with gated memory buffers, or - more recently - imposed constraints that ensure convergence to a fixed point or restrict (the eigenspectrum of) the recurrence matrix. Such constraints, however, convey severe limitations on the expressivity of the RNN. Essential intrinsic dynamics such as multistability or chaos are disabled. This is inherently at disaccord with the chaotic nature of many, if not most, time series encountered in nature and society. It is particularly problematic in scientific applications where one aims to reconstruct the underlying dynamical system. Here we offer a comprehensive theoretical treatment of this problem by relating the loss gradients during RNN training to the Lyapunov spectrum of RNN-generated orbits. We mathematically prove that RNNs producing stable equilibrium or cyclic behavior have bounded gradients, whereas the gradients of RNNs with chaotic dynamics always diverge. Based on these analyses and insights we suggest ways of how to optimize the training process on chaotic data according to the system's Lyapunov spectrum, regardless of the employed RNN architecture

Evaluating outcomes of medication-related interventions from the “Seniors At risk for Falls after Emergency Room visit” (SAFER) pilot project

Primary Author: Ling J. Zhan, PharmD Co-Authors: Sharon Leigh, PharmD BCPS, Mary Beth Kuebrich, MS, AGPCNP-BC, Clara Mikhaeil, PharmD, BCPS, Colleen M. Casey, PhD, ANP-BC Location: Providence Health & Services, Portland, Oregon Title: Evaluating outcomes of medication-related interventions from the “Seniors At risk for Falls after Emergency Room visit” (SAFER) pilot project Purpose: Falls are the leading cause of injury in older adults, resulting in decreased mobility, loss of independence, and increased health care costs. Even a single fall puts an older adult at higher risk for future falls. Despite numerous studies showing evidence that multifactorial fall risk interventions are effective in decreasing fall risk, even older adults who have an injurious fall often do not receive meaningful interventions to mitigate their fall risk. This study evaluated the impact of medication-related interventions for older adults who had a fall-related ED visit, as part of a larger study of multifactorial fall-risk interventions in the primary care setting. Methods: This study was approved by the Providence-Oregon Institutional Review Board. This retrospective chart review studied a subset of patients enrolled in the SAFER pilot project who presented to an ED following a fall. Included patients were 75 years or older and taking at least one high-risk medication (HRM) that is associated with increased risk for falls. Patients were enrolled in the SAFER pilot from December 2018 to June 2019. Eligible patients received a comprehensive medication review by a clinical pharmacist; some also received a Geriatric consult that included medication recommendations. Medication recommendations were then forwarded to the clinic’s Primary Care Provider (PCP) and Registered Nurse for follow up. The parent study used a matched control design to compare SAFER interventions with usual care; this study did not include a comparison to the control group. Study outcomes included: overall burden of high-risk medications, number of high-risk medications discontinued or tapered, initiation of osteoporosis treatment or prevention measures, changes in blood pressure (BP) or hemoglobin A1c goals, and overall reduction in polypharmacy. The study also evaluated to what degree medication-related recommendations were adopted by the PCP over a minimum follow-up period of 7 months. Results: Overall, 50 patients underwent chart review with 4 patients not meeting inclusion criteria; 46 patients were on HRM (average 4.3 HRM/person) and included in the final analysis. Of those patients, 25 (54%) received a PharmD consult. For these 25 patients, 117 medication-related recommendations were made by the Geriatric and Clinical Pharmacy teams. Of those, a total of 52 (44%) changes were implemented by the PCP: 17 HRMs were discontinued, 9 taper/cross-tapered, and 17 osteoporosis-related initiated. BP and A1c goals on patient’s problem list were not clearly defined for 69% and 50% of patients, respectively. Conclusion: Medication optimization and reduction of HRM was effective in patients receiving a PharmD consult. The most accepted recommendations included ordering DEXA, orthostatic BP testing, adding Vitamin D, and discontinuing opioids. Not every patient who qualified received a PharmD consult, suggesting that more medication changes could have been implemented had PharmDs been involved. The process of referring to a PharmD for a consult will need to be reviewed. Given that these patients are at high risk to fall, BP and A1c goals should be clarified and perhaps more lenient goals may be indicated. In addition, these results should be compared with the matched-control group of the parent study to determine the value of reducing HRM use in older patients at high risk of falls.https://digitalcommons.psjhealth.org/pharmacy_PGY1/1007/thumbnail.jp

Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity

<p>Abstract</p> <p>Background</p> <p>Originating from Africa, India, and the Middle East, frankincense oil has been important both socially and economically as an ingredient in incense and perfumes for thousands of years. Frankincense oil is prepared from aromatic hardened gum resins obtained by tapping <it>Boswellia </it>trees. One of the main components of frankincense oil is boswellic acid, a component known to have anti-neoplastic properties. The goal of this study was to evaluate frankincense oil for its anti-tumor activity and signaling pathways in bladder cancer cells.</p> <p>Methods</p> <p>Frankincense oil-induced cell viability was investigated in human bladder cancer J82 cells and immortalized normal bladder urothelial UROtsa cells. Temporal regulation of frankincense oil-activated gene expression in bladder cancer cells was identified by microarray and bioinformatics analysis.</p> <p>Results</p> <p>Within a range of concentration, frankincense oil suppressed cell viability in bladder transitional carcinoma J82 cells but not in UROtsa cells. Comprehensive gene expression analysis confirmed that frankincense oil activates genes that are responsible for cell cycle arrest, cell growth suppression, and apoptosis in J82 cells. However, frankincense oil-induced cell death in J82 cells did not result in DNA fragmentation, a hallmark of apoptosis.</p> <p>Conclusion</p> <p>Frankincense oil appears to distinguish cancerous from normal bladder cells and suppress cancer cell viability. Microarray and bioinformatics analysis proposed multiple pathways that can be activated by frankincense oil to induce bladder cancer cell death. Frankincense oil might represent an alternative intravesical agent for bladder cancer treatment.</p

Model Based Evaluation of Structural Measures Impact on the Inundation Area of Wadi Driven Flash Floods,.Case study of Wadi Dahab, Sinai Peninsula, Egypt

The Second International Symposium on Flash Floods in Wadi Systems: 25-27 October 2016. Technische Universität Berlin, Campus El Gouna, Egypt