Forecast dataset associated with “From Random Forests to Flood Forecasts: A Research to Operations Success Story”

Gridded forecasts from the Colorado State University-Machine Learning Probabilities (CSU-MLP) system for excessive rainfall prediction over the continental United States. The dataset includes probabilistic forecasts for days 1, 2, and 3 from the 2017, 2019, and 2020 versions of the CSU-MLP forecast system. For the day 2 and 3 forecasts, daily forecasts are included from 19 June 2018 through 15 October 2020; for day-1 forecasts a period from 15 March 2019 through 15 October 2020 is used.Because excessive rainfall is poorly defined and difficult to forecast, there is a need for tools for Weather Prediction Center (WPC) forecasters to use when generating Excessive Rainfall Outlooks (EROs), which are issued for the contiguous United States at lead times of 1--3 days. To address this need, a probabilistic forecast system for excessive rainfall, known as the Colorado State University-Machine Learning Probabilities (CSU-MLP) system, was developed based on ensemble reforecasts, precipitation observations, and machine learning algorithms, specifically random forests. The CSU-MLP forecasts were designed to emulate the EROs, with the goal being a tool that forecasters can use as a ``first guess'' in the ERO forecast process. Resulting from close collaboration between CSU and WPC and evaluation at the Flash Flood and Intense Rainfall experiment, iterative improvements were made to the forecast system and it was transitioned into operational use at WPC. Quantitative evaluation shows that the CSU-MLP forecasts are skillful and reliable, and they are now being used as a part of the WPC forecast process. This project represents an example of a successful research-to-operations transition, and highlights the potential for machine learning and other post-processing techniques to improve operational predictions.This research and operational transition was supported by NOAA Joint Technology Transfer Initiative grants NA16OAR4590238 and NA18OAR4590378

Quantum mutual information and the one-time pad

Alice and Bob share a correlated composite quantum system AB. If AB is used as the key for a one-time pad cryptographic system, we show that the maximum amount of information that Alice can send securely to Bob is the quantum mutual information of AB.Comment: 11 pages, LaTe

Pain Medication Management Processes Used by Oncology Outpatients and Family Caregivers Part II: Home and Lifestyle Contexts

Context—Despite the increasing complexity of medication regimens for persistent cancer pain, little is known about how oncology outpatients and their family caregivers manage pain medications at home. Objectives—To describe the day-to-day management of pain medications from the perspectives of oncology outpatients and their family caregivers who participated in a randomized clinical trial (RCT) of a psycho-educational intervention called the Pro-Self © Plus Pain Control Program. In this article, we focus on pain medication management in the context of highly individualized home environments and lifestyles. Methods—This qualitative study was conducted as part of a RCT in which an embedded mixed methods research design was used. Audio-recorded dialogue among patients, family caregivers, and intervention nurses was analyzed using qualitative research methods. Results—Home and lifestyle contexts for managing pain medications included highly individualized home environments, work and recreational activities, personal routines, and family characteristics. Pain medication management processes particularly relevant in these contexts included understanding, organizing, storing, scheduling, remembering, and taking the medications. With the exception of their interactions with the intervention nurses, most study participants had little involvement with clinicians as they worked through these processes. Conclusion—Pain medication management is an ongoing multidimensional process, each step of which has to be mastered by patients and family caregivers when cancer treatment and supportive care is provided on an outpatient basis. Realistic patient- and family-centered skill-building interventions are needed to achieve effective and safe pain medication management in the contexts of individual home environments and lifestyles

Pain Medication Management Processes Used by Oncology Outpatients and Family Caregivers Part I: Health Systems Contexts

Context—Oncology patients with persistent pain treated in outpatient settings and their family caregivers have significant responsibility for managing pain medications. However, little is known about their practical, day-to-day experiences with pain medication management. Objective—To describe day-to-day pain medication management from the perspectives of oncology outpatients and their family caregivers who participated in a randomized clinical trial of a psycho-educational intervention called the Pro-Self© Plus Pain Control Program. In this article, we focus on pain medication management by patients and family caregivers in the context of multiple, complex health systems. Methods—We qualitatively analyzed audio-recorded intervention sessions that included extensive dialogue between patients, family caregivers, and nurses about pain medication management during the 10-week intervention. Results—The health systems context for pain medication management included multiple complex systems for clinical care, reimbursement, and regulation of analgesic prescriptions. Pain medication management processes particularly relevant to this context were getting prescriptions and obtaining medications. Responsibilities that fell primarily to patients and family caregivers included facilitating communication and coordination among multiple clinicians, overcoming barriers to access, and serving as a final safety checkpoint. Significant effort was required of patients and family caregivers to insure safe and effective pain medication management. Conclusion—Health systems issues related to access to needed analgesics, medication safety in outpatient settings, and the effort expended by oncology patients and their family caregivers require more attention in future research and healthcare reform initiatives

Universal geometric approach to uncertainty, entropy and information

It is shown that for any ensemble, whether classical or quantum, continuous or discrete, there is only one measure of the "volume" of the ensemble that is compatible with several basic geometric postulates. This volume measure is thus a preferred and universal choice for characterising the inherent spread, dispersion, localisation, etc, of the ensemble. Remarkably, this unique "ensemble volume" is a simple function of the ensemble entropy, and hence provides a new geometric characterisation of the latter quantity. Applications include unified, volume-based derivations of the Holevo and Shannon bounds in quantum and classical information theory; a precise geometric interpretation of thermodynamic entropy for equilibrium ensembles; a geometric derivation of semi-classical uncertainty relations; a new means for defining classical and quantum localization for arbitrary evolution processes; a geometric interpretation of relative entropy; and a new proposed definition for the spot-size of an optical beam. Advantages of the ensemble volume over other measures of localization (root-mean-square deviation, Renyi entropies, and inverse participation ratio) are discussed.Comment: Latex, 38 pages + 2 figures; p(\alpha)->1/|T| in Eq. (72) [Eq. (A10) of published version

Failure to establish HIV care: characterizing the no show phenomenon

It is estimated that up to one-third of persons with known human immunodeficiency virus (HIV) infection in the United States are not engaged in care. We evaluated factors associated with patients\u27 failure to establish outpatient HIV care at our clinic and found that females, racial minorities, and patients lacking private health insurance were more likely to be no shows. At the clinic level, longer waiting time from the call to schedule a new patient visit to the appointment date was associated with failure to establish care. Because increased numbers of patients will be in need of outpatient HIV care as a result of recent Centers for Disease Control and Prevention guidelines advocating routine HIV testing, it is imperative that strategies to improve access are developed to overcome the no show phenomenon

Ceramide levels in blood plasma correlate with major depressive disorder severity and its neutralization abrogates depressive behavior in mice

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced models of MDD. These blood plasma ceramide levels correlated with the severity of MDD in human patients and were independent of age, sex, or body mass index. In addition, intravenous injection of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and intravenous injection of blood plasma from mice with MDD induced depression-like behavior in untreated mice, which was abrogated by ex vivo preincubation of the plasma with anti-ceramide antibodies or ceramidase. Mechanistically, we demonstrate that ceramide accumulated in endothelial cells of the hippocampus of stressed mice, evidenced by the quantitative measurement of ceramide in purified hippocampus endothelial cells. We found ceramide inhibited the activity of phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus. Finally, we show intravenous injection of PLD or phosphatidic acid abrogated MDD, indicating the significance of this pathway in MDD pathogenesis. Our data indicate that ceramide controls PLD activity and phosphatidic acid formation in hippocampal endothelial cells and thereby mediates MDD. We propose that neutralization of plasma ceramide could represent a rapid-acting targeted treatment for MDD

Acid Sphingomyelinase Deficiency Ameliorates Farber Disease

Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients

Dysfunctional brain dynamics and their origin in Lewy body dementia.

Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia and is characterized by transient clinical symptoms such as fluctuating cognition, which might be driven by dysfunction of the intrinsic dynamic properties of the brain. In this context we investigated whole-brain dynamics on a subsecond timescale in 42 Lewy body dementia compared to 27 Alzheimer's disease patients and 18 healthy controls using an EEG microstate analysis in a cross-sectional design. Microstates are transiently stable brain topographies whose temporal characteristics provide insight into the brain's dynamic repertoire. Our additional aim was to explore what processes in the brain drive microstate dynamics. We therefore studied associations between microstate dynamics and temporal aspects of large-scale cortical-basal ganglia-thalamic interactions using dynamic functional MRI measures given the putative role of these subcortical areas in modulating widespread cortical function and their known vulnerability to Lewy body pathology. Microstate duration was increased in Lewy body dementia for all microstate classes compared to Alzheimer's disease (P < 0.001) and healthy controls (P < 0.001), while microstate dynamics in Alzheimer's disease were largely comparable to healthy control levels, albeit with altered microstate topographies. Correspondingly, the number of distinct microstates per second was reduced in Lewy body dementia compared to healthy controls (P < 0.001) and Alzheimer's disease (P < 0.001). In the dementia with Lewy bodies group, mean microstate duration was related to the severity of cognitive fluctuations (ρ = 0.56, PFDR = 0.038). Additionally, mean microstate duration was negatively correlated with dynamic functional connectivity between the basal ganglia (r = - 0.53, P = 0.003) and thalamic networks (r = - 0.38, P = 0.04) and large-scale cortical networks such as visual and motor networks in Lewy body dementia. The results indicate a slowing of microstate dynamics and disturbances to the precise timing of microstate sequences in Lewy body dementia, which might lead to a breakdown of the intricate dynamic properties of the brain, thereby causing loss of flexibility and adaptability that is crucial for healthy brain functioning. When contrasted with the largely intact microstate dynamics in Alzheimer's disease, the alterations in dynamic properties in Lewy body dementia indicate a brain state that is less responsive to environmental demands and might give rise to the apparent slowing in thinking and intermittent confusion which typify Lewy body dementia. By using Lewy body dementia as a probe pathology we demonstrate a potential link between dynamic functional MRI fluctuations and microstate dynamics, suggesting that dynamic interactions within the cortical-basal ganglia-thalamic loop might play a role in the modulation of EEG dynamics