Income Smoothing over the Business Cycle: Changes in Banks’ Coordinated Management of Provisions for Loan Losses and Loan Charge-offs from the Pre-1990 Bust to the 1990s Boom

We provide evidence that banks smooth income by managing provisions for loan losses and loan charge-offs in a coordinated fashion that varies across the bust and boom phases of the business cycle and across homogeneous and heterogeneous loan types. In particular, during the 1990s boom, we predict and find that banks accelerated provisioning for loan losses and made this less obvious by accelerating loan charge-offs, especially for homogenous loans for which charge-offs are determined using number-of-days-past-due rules. We also provide evidence that the valuation implications of banks’ provisions for loan losses and loan charge-offs vary across the phases of the business cycle and loan types reflecting the effect of these factors on banks’ income smoothing. In particular, during the 1990s boom, we predict and find that charge-offs of homogenous loans have a positive association with current returns and future cash flows, because these charge-offs are recorded primarily by healthy banks with good future prospects reducing over-stated allowances for loan losses. We also predict and find that these charge-offs have a positive association with future returns that is explained by their positive association with future net income and recoveries. Our results are consistent with the market only partially appreciating healthy banks’ overstatement of charge-offs of homogeneous loans based on number-of-days-past-due rules during the 1990s boom, because of the perceived non-discretionary nature of these charge-offs

Temporal Subsampling Diminishes Small Spatial Scales in Recurrent Neural Network Emulators of Geophysical Turbulence

The immense computational cost of traditional numerical weather and climate models has sparked the development of machine learning (ML) based emulators. Because ML methods benefit from long records of training data, it is common to use datasets that are temporally subsampled relative to the time steps required for the numerical integration of differential equations. Here, we investigate how this often overlooked processing step affects the quality of an emulator's predictions. We implement two ML architectures from a class of methods called reservoir computing: (1) a form of Nonlinear Vector Autoregression (NVAR), and (2) an Echo State Network (ESN). Despite their simplicity, it is well documented that these architectures excel at predicting low dimensional chaotic dynamics. We are therefore motivated to test these architectures in an idealized setting of predicting high dimensional geophysical turbulence as represented by Surface Quasi-Geostrophic dynamics. In all cases, subsampling the training data consistently leads to an increased bias at small spatial scales that resembles numerical diffusion. Interestingly, the NVAR architecture becomes unstable when the temporal resolution is increased, indicating that the polynomial based interactions are insufficient at capturing the detailed nonlinearities of the turbulent flow. The ESN architecture is found to be more robust, suggesting a benefit to the more expensive but more general structure. Spectral errors are reduced by including a penalty on the kinetic energy density spectrum during training, although the subsampling related errors persist. Future work is warranted to understand how the temporal resolution of training data affects other ML architectures

On-stack replacement, distilled

On-stack replacement (OSR) is essential technology for adaptive optimization, allowing changes to code actively executing in a managed runtime. The engineering aspects of OSR are well-known among VM architects, with several implementations available to date. However, OSR is yet to be explored as a general means to transfer execution between related program versions, which can pave the road to unprecedented applications that stretch beyond VMs. We aim at filling this gap with a constructive and provably correct OSR framework, allowing a class of general-purpose transformation functions to yield a special-purpose replacement. We describe and evaluate an implementation of our technique in LLVM. As a novel application of OSR, we present a feasibility study on debugging of optimized code, showing how our techniques can be used to fix variables holding incorrect values at breakpoints due to optimizations

Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests

Collider signals from slow decays in supersymmetric models with an intermediate-scale solution to the mu problem

The problem of the origin of the mu parameter in the Minimal Supersymmetric Standard Model can be solved by introducing singlet supermultiplets with non-renormalizable couplings to the ordinary Higgs supermultiplets. The Peccei-Quinn symmetry is broken at a scale which is the geometric mean between the weak scale and the Planck scale, yielding a mu term of the right order of magnitude and an invisible axion. These models also predict one or more singlet fermions which have electroweak-scale masses and suppressed couplings to MSSM states. I consider the case that such a singlet fermion, containing the axino as an admixture, is the lightest supersymmetric particle. I work out the relevant couplings in several of the simplest models of this type, and compute the partial decay widths of the next-to-lightest supersymmetric particle involving leptons or jets. Although these decays will have an average proper decay length which is most likely much larger than a typical collider detector, they can occasionally occur within the detector, providing a striking signal. With a large sample of supersymmetric events, there will be an opportunity to observe these decays, and so gain direct information about physics at very high energy scales.Comment: 24 pages, LaTeX, 4 figure

Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders

Temporal Ordering in Endocytic Clathrin-Coated Vesicle Formation via AP2 Phosphorylation.

Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells' limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the μ2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime. μ2Thr156 phosphorylation favors a new, cargo-bound conformation of AP2 and simultaneously creates a binding platform for the endocytic NECAP proteins but without significantly altering AP2's cargo affinity in vitro. We describe the structural bases of both. NECAP arrival at CCPs parallels that of clathrin and increases with μ2Thr156 phosphorylation. In turn, NECAP recruits drivers of late stages of CCP formation, including SNX9, via a site distinct from where NECAP binds AP2. Disruption of the different modules of this phosphorylation-based temporal regulatory system results in CCP maturation being delayed and/or stalled, hence impairing global rates of CME

Randomised Controlled Trial of Lactobacillus Rhamnosus (LGG) Versus Placebo in Children Presenting to the Emergency Department with Acute Gastroenteritis: the PECARN Probiotic Study Protocol.

INTRODUCTION: Acute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration and infection control; no disease-modifying interventions exist. Probiotics, defined as live microorganisms beneficial to the host, have shown promise in improving AGE outcomes, but existing studies have sufficient limitations such that the use of probiotics cannot currently be recommended with confidence. Here we present the methods of a large, rigorous, randomised, double-blind placebo-controlled study to assess the effectiveness and side effect profile of Lactobacillus rhamnosus GG (LGG) (ATCC 53103) in children with AGE. METHODS AND ANALYSIS: The study is being conducted in 10 US paediatric emergency departments (EDs) within the federally funded Pediatric Emergency Care Applied Research Network, in accordance with current SPIRIT and CONSORT statement recommendations. We will randomise 970 children presenting to participating EDs with AGE to either 5 days of treatment with LGG (10(10)colony-forming unit twice a day) or placebo between July 2014 to December 2017. The main outcome is the occurrence of moderate-to-severe disease over time, as defined by the Modified Vesikari Scale. We also record adverse events and side effects related to the intervention. We will conduct intention-to-treat analyses and use an enrichment design to restore the statistical power in case the presence of a subpopulation with a substantially low treatment effect is identified. ETHICS AND DISSEMINATION: Institutional review board approval has been obtained at all sites, and data and material use agreements have been established between the participating sites. The results of the trial will be published in peer-reviewed journals. A deidentified public data set will be made available after the completion of all study procedures. TRIAL REGISTRATION NUMBER: NCT01773967