Do unbalanced data have a negative effect on LDA?

For two-class discrimination, Xie and Qiu [The effect of imbalanced data sets on LDA: a theoretical and empirical analysis, Pattern Recognition 40 (2) (2007) 557–562] claimed that, when covariance matrices of the two classes were unequal, a (class) unbalanced data set had a negative effect on the performance of linear discriminant analysis (LDA). Through re-balancing 10 real-world data sets, Xie and Qiu [The effect of imbalanced data sets on LDA: a theoretical and empirical analysis, Pattern Recognition 40 (2) (2007) 557–562] provided empirical evidence to support the claim using AUC (Area Under the receiver operating characteristic Curve) as the performance metric. We suggest that such a claim is vague if not misleading, there is no solid theoretical analysis presented in Xie and Qiu [The effect of imbalanced data sets on LDA: a theoretical and empirical analysis, Pattern Recognition 40 (2) (2007) 557–562], and AUC can lead to a quite different conclusion from that led to by misclassification error rate (ER) on the discrimination performance of LDA for unbalanced data sets. Our empirical and simulation studies suggest that, for LDA, the increase of the median of AUC (and thus the improvement of performance of LDA) from re-balancing is relatively small, while, in contrast, the increase of the median of ER (and thus the decline in performance of LDA) from re-balancing is relatively large. Therefore, from our study, there is no reliable empirical evidence to support the claim that a (class) unbalanced data set has a negative effect on the performance of LDA. In addition, re-balancing affects the performance of LDA for data sets with either equal or unequal covariance matrices, indicating that having unequal covariance matrices is not a key reason for the difference in performance between original and re-balanced data

Therapeutic targeting of ALS pathways: refocusing an incomplete picture

© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes have been observed with only modest effects. Along with an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution of more sophisticated and diverse in vitro and in vivo preclinical modeling platforms, as well as clinical trial designs. We highlight proposed pathological pathways that have been major therapeutic targets for investigational compounds. It is likely that the failures of so many of these therapeutic compounds may not have occurred because of lack of efficacy but rather because of a lack of preclinical modeling that would help define an appropriate disease pathway, as well as a failure to establish target engagement. These challenges are compounded by shortcomings in clinical trial design, including lack of biomarkers that could predict clinical success and studies that are underpowered. Although research investments have provided abundant insights into new ALS-relevant pathways, most have not yet been developed more fully to result in clinical study. In this review, we detail some of the important, well-established pathways, the therapeutics targeting them, and the subsequent clinical design. With an understanding of some of the shortcomings in translational efforts over the last three decades of ALS investigation, we propose that scientists and clinicians may choose to revisit some of these therapeutic pathways reviewed here with an eye toward improving preclinical modeling, biomarker development, and the investment in more sophisticated clinical trial designs.Research funding: Cytokinetics National Institutes of Health, USA. Grant Number: 5R01NS117604-03info:eu-repo/semantics/publishedVersio

Return times, recurrence densities and entropy for actions of some discrete amenable groups

Results of Wyner and Ziv and of Ornstein and Weiss show that if one observes the first k outputs of a finite-valued ergodic process, then the waiting time until this block appears again is almost surely asymptotic to $2^{hk}$, where $h$ is the entropy of the process. We examine this phenomenon when the allowed return times are restricted to some subset of times, and generalize the results to processes parameterized by other discrete amenable groups. We also obtain a uniform density version of the waiting time results: For a process on $s$ symbols, within a given realization, the density of the initial $k$-block within larger $n$-blocks approaches $2^{-hk}$, uniformly in $n>s^k$, as $k$ tends to infinity. Again, similar results hold for processes with other indexing groups.Comment: To appear in Journal d'Analyse Mathematiqu

The interferon-induced exonuclease ISG20 exerts antiviral activity through upregulation of type I interferon response proteins

The host immune responses to infection lead to the production of type I interferon (IFN), and the upregulation of interferon-stimulated genes (ISGs) reduces virus replication and virus dissemination within a host. Ectopic expression of the interferon-induced 20-kDa exonuclease ISG20 suppressed replication of chikungunya virus and Venezuelan equine encephalitis virus, two mosquito-vectored RNA alphaviruses. Since the replication of alphavirus genomes occurs exclusively in the cytoplasm, the mechanism of nucleus-localized ISG20 inhibition of replication is unclear. In this study, we determined that ISG20 acts as a master regulator of over 100 genes, many of which are ISGs. Specifically, ISG20 upregulated IFIT1 genes and inhibited translation of the alphavirus genome. Furthermore, IFIT1-sensitive alphavirus replication was increased in Isg20−/− mice compared to the replication of wild-type viruses but not in cells ectopically expressing ISG20. We propose that ISG20 acts as an indirect regulator of RNA virus replication in the cytoplasm through the upregulation of many other ISGs.Type I interferon (IFN)-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20-kDa ISG ISG20 is a nuclear 3′–5′ exonuclease with preference for single-stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20−/− mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20−/− mice compared to that of wild-type viruses but not in cells ectopically expressing ISG20. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expression of other ISGs that inhibit translation and possibly other activities in the replication cycle

Complete High Temperature Expansions for One-Loop Finite Temperature Effects

We develop exact, simple closed form expressions for partition functions associated with relativistic bosons and fermions in odd spatial dimensions. These expressions, valid at high temperature, include the effects of a non-trivial Polyakov loop and generalize well-known high temperature expansions. The key technical point is the proof of a set of Bessel function identities which resum low temperature expansions into high temperature expansions. The complete expressions for these partition functions can be used to obtain one-loop finite temperature contributions to effective potentials, and thus free energies and pressures.Comment: 9 pages, RevTeX, no figures. To be published in Phys. Rev D. v2 has revised introduction and conclusions, plus a few typographical errors are corrected; v3 corrects one typ

The Relative and Unique Contributions of Emotion Dysregulation and Impulsivity to Posttraumatic Stress Disorder Among Substance Dependent Inpatients

Background: Despite elevated rates of posttraumatic stress disorder (PTSD) among substance use disorder (SUD) patients, as well as the clinical relevance of this co-occurrence, few studies have examined psychological factors associated with a PTSD–SUD diagnosis. Two factors worth investigating are emotion dysregulation and impulsivity, both of which are associated with PTSD and SUDs. Therefore, this study examined associations between PTSD and facets of emotion dysregulation and impulsivity within a sample of trauma-exposed SUD inpatients. Methods: Participants were an ethnically diverse sample of 205 SUD patients in residential substance abuse treatment. Patients were administered diagnostic interviews and completed a series of questionnaires. Results: Patients with PTSD (n = 58) reported significantly higher levels of negative urgency (i.e., the tendency to engage in impulsive behaviors when experiencing negative affect) and lower sensation seeking, as well as higher levels of emotion dysregulation and the specific dimensions of lack of emotional acceptance, difficulties engaging in goal-directed behavior when upset, difficulties controlling impulsive behaviors when distressed, limited access to effective emotion regulation strategies, and lack of emotional clarity. Further, overall emotion dysregulation emerged as a significant predictor of PTSD status, accounting for unique variance in PTSD status above and beyond facets of impulsivity (as well as other relevant covariates). Conclusions: Results suggest that emotion dysregulation may contribute to the development, maintenance, and/or exacerbation of PTSD and highlight the potential clinical utility of targeting emotion dysregulation among SUD patients with PTSD

Nutritional Status of Children with Attention Deficit Hyperactivity Disorder: A Pilot Study

Objectives. This is a pilot study of the dietary intake and nutrient status of children with Attention Deficit Hyperactivity Disorder (ADHD). Method. Nutritional assessment of 43 children aged 6–12 with ADHD was performed using a 3-day food record, 24-hour recall, and serum assessors. Results. Macronutrient intake and consumption of Low-Nutrient Foods were comparable to population norms; however, 66% were found to be deficient in zinc and 23% in copper. Conclusions. This pilot study reports the food intake and nutrient status of children with ADHD and shows a predisposition for low zinc and copper status in ADHD

Global and local relaxation of a spin-chain under exact Schroedinger and master-equation dynamics

We solve the Schroedinger equation for an interacting spin-chain locally coupled to a quantum environment with a specific degeneracy structure. The reduced dynamics of the whole spin-chain as well as of single spins is analyzed. We show, that the total spin-chain relaxes to a thermal equilibrium state independently of the internal interaction strength. In contrast, the asymptotic states of each individual spin are thermal for weak but non-thermal for stronger spin-spin coupling. The transition between both scenarios is found for couplings of the order of $0.1 \times \Delta E$, with $\Delta E$ denoting the Zeeman-splitting. We compare these results with a master equation treatment; when time averaged, both approaches lead to the same asymptotic state and finally with analytical results.Comment: RevTeX, 8 pages, 14 figures, added DOI and forgotten reference

Case Report Megace Mystery: A Case of Central Adrenal Insufficiency

Megestrol acetate (MA) is a synthetic progestin with both antineoplastic and orexigenic properties. In addition to its effects on the progesterone receptor, MA also binds the glucocorticoid receptor. Some patients receiving MA therapy have been reported to develop clinical features of glucocorticoid excess, while others have experienced the clinical syndrome of cortisol deficiencyeither following withdrawal of MA therapy or during active treatment. We describe a patient who presented with clinical and biochemical features of central adrenal insufficiency. Pituitary function was otherwise essentially normal, and the etiology of the isolated ACTH suppression was initially unclear. The use of an exogenous glucocorticoid was suspected but was initially denied by the patient; ultimately, the culprit medication was uncovered when a synthetic steroid screen revealed the presence of MA. The patient's symptoms improved after she was switched to hydrocortisone. Clinicians should be aware of the potential effects of MA on the hypothalamic-pituitary-adrenal (HPA) axis

Local Versus Global Thermal States: Correlations and the Existence of Local Temperatures

We consider a quantum system consisting of a regular chain of elementary subsystems with nearest neighbor interactions and assume that the total system is in a canonical state with temperature $T$. We analyze under what condition the state factors into a product of canonical density matrices with respect to groups of $n$ subsystems each, and when these groups have the same temperature $T$. While in classical mechanics the validity of this procedure only depends on the size of the groups $n$, in quantum mechanics the minimum group size $n_{min}$ also depends on the temperature $T$! As examples, we apply our analysis to a harmonic chain and different types of Ising spin chains. We discuss various features that show up due to the characteristics of the models considered. For the harmonic chain, which successfully describes thermal properties of insulating solids, our approach gives a first quantitative estimate of the minimal length scale on which temperature can exist: This length scale is found to be constant for temperatures above the Debye temperature and proportional to $T^{-3}$ below.Comment: 12 pages, 5 figures, discussion of results extended, accepted for publication in Phys. Rev.