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Mice deficient in GHR (growth hormone receptor; ghr KO) have a dramatic lifespan extension and elevated levels of hepatic chaperone-mediated autophagy (CMA). Using quantitative proteomics to identify protein changes in purified liver lysosomes and whole liver lysates, we provide evidence that elevated CMA in ghr KO mice downregulates proteins involved in ribosomal structure, translation initiation and elongation, and nucleocytosolic acetyl-coA production. Following up on these initial proteomics findings, we used a cell culture approach to show that CMA is necessary and sufficient to regulate the abundance of ACLY and ACSS2, the two enzymes that produce nucleocytosolic (but not mitochondrial) acetyl-coA. Inhibition of CMA in NIH3T3 cells has been shown to lead to aberrant accumulation of lipid droplets. We show that this lipid droplet phenotype is rescued by knocking down ACLY or ACSS2, suggesting that CMA regulates lipid droplet formation by controlling ACLY and ACSS2. This evidence leads to a model of how constitutive activation of CMA can shape specific metabolic pathways in long-lived endocrine mutant mice. Abbreviations: CMA: chaperone-mediated autophagy; DIA: data-independent acquisition; ghr KO: growth hormone receptor knockout; GO: gene ontology; I-WAT: inguinal white adipose tissue; KFERQ: a consensus sequence resembling Lys-Phe-Glu-Arg-Gln; LAMP2A: lysosomal-associated membrane protein 2A; LC3-I: non-lipidated MAP1LC3; LC3-II: lipidated MAP1LC3; PBS: phosphate-buffered saline; PI3K: phosphoinositide 3-kinase

Background: The COVID -19 pandemic spread rapidly across the globe, making a land-fall on the Nigerian geo-space in early 2020. Key presenting features were; fever, dry cough, fatigue, myalgia, headache, sore-throat, abdominal pain, diarrhea, dyspnoea amongst others, with a clinical spectrum ranging from mild through severe forms. Aside infection control and supportive care, there was no specific therapy until trials with Remdesivir. Studies have described limited epidemiological findings, presentations and outcomes of COVID patients in Nigeria and elsewhere, but not for the Federal Capital Territory, (FCT) specifically Abuja, the Nation's capital city and the second epicenter of the pandemic in Nigeria. The objective of this study therefore, was to describe the Clinical and demographic characteristics of the patients admitted at the Asokoro District Hospital (ADH), Abuja. Methods: Retrospective study that used records of patients admitted, between April and September 2020. Data include; Socio-demographics, medical history, exposure, residential area, co-morbidities, symptoms, signs, treatment measures, duration of hospital stay and outcomes. Results: 270 patients were enrolled for this study. 170(63%) males and 100(37%) females. Mean age was 40.03+13.5years. Forty-one(15.2%) had travel history while 99(36.7%) had contact with confirmed cases. Majority of the patients were married(63.33%), and had tertiary education(74.82%). Commonest symptoms were cough(43.33%), fever(36.67%), headaches(32.22%) and fatigue(31.48%). The duration of stay at the ADH ranged from 2 hours to 28 days. Conclusion: Our patients were young, mainly of the upper class, educated people with mild to severe disease. There was one death, a case with multiple comorbid factors. Keywords: Abuja-Nigeria; COVID patients; Socio-demographics; clinical features; outcomes.

Compartment models are a widely used class of models that are useful when considering the flow of objects, people, or energy between different labeled states, referred to as compartments. Classic e...

Introduction La question de la survenue de maladies inflammatoires chroniques de l’intestin (MICI) de novo (MICI-DN) sous inhibiteurs de l’interleukine 17 (anti-IL 17) a ete soulevee a partir des donnees des essais pivots. Les objectifs principaux de l’etude MISSIL (Maladies Inflammatoires chroniques de l’Intestin SouS anti-IL 17) etaient de decrire les cas de MICI-DN sous anti-IL17 en France, d’identifier d’eventuels facteurs de risque et d’evaluer l’incidence des MICI-DN chez les patients (pts) sous anti-IL 17 en France. Patients et methodes Un registre national collectant les cas de MICI-DN chez les pts sous anti-IL 17 a ete mis en place entre 2016 et 2019 sous l’egide du CRI, du GETAID et de ResoPso. Une etude cas-temoins a ete realisee avec 2 temoins apparies sur l’âge (±8 ans), le sexe et la pathologie. Les comparaisons des cas aux temoins ont ete realisees grâce a des modeles lineaires mixtes generalises. Une regression logistique conditionnelle a ete utilisee en cas d’echec de la convergence des modeles lineaires mixes en incluant les blocs apparies comme effet aleatoire. Les taux d’incidence annuels de MICI-DN (en 100 pts-annees [PA]) ont ete calcules a partir du nombre de cas annuels declares de MICI-DN au numerateur, et le nombre annuel de PA sous anti-IL 17 (chiffres fournis par l’industrie pharmaceutique) au denominateur. Resultats 31 cas de MICI-DN sous secukinumab (SEK) ont ete recueillis entre janvier 2016 et decembre 2019 : 27 pts ayant une spondyloarthrite et 4 ayant un psoriasis. Aucun cas n’a ete declare sous ixekizumab. L’âge moyen etait de 49,2 ± 14,6 ans. 14/31 etaient des femmes, 10/25 avaient une sacro-iliite radiographique (SI-Rx) et 15/25 une sacro-iliite IRM (SI-IRM). Seuls 4 pts etaient naifs de biotherapies. Le delai median de survenue des symptomes de MICI-DN etait de 4,0 (1,5-7,5) mois apres initiation du SEK. Les symptomes principaux etaient la diarrhee et la perte de poids. La CRP mediane a la survenue des symptomes etait de 68,0 (34,0-177,5) mg/L. Les traitements recus apres arret du SEK (chez tous les pts) etaient : une corticotherapie chez 19 pts, un anti-TNFα chez 21 pts, l’ustekinumab chez 7 pts et la colectomie chez 2 pts, 3 pts ayant recu plusieurs biotherapies. L’evolution etait favorable pour 29/31 pts avec une remission (17/31), une amelioration (7/31) ou une stabilisation (5/31), 2 pts etant decedes : un infarctus massif du myocarde dans un contexte de denutrition majeure liee a la MICI-DN et deces des suites de la colectomie. L’incidence des MICI-DN etait calculee a 0,69 % (7/1010) en 2016, de 0,23 % (11/4704) en 2017, 0,11 % (7/6550) en 2018 et 0,08 % (6/7951) en 2019. Dans l’etude cas-temoins, la presence d’une SI-RX (OR = 0,65, IC95 % 0,45-0,94, p = 0,022), un antecedent de traitement par etanercept (ETN) (OR = 0,33, IC95 % 0,14-0,80, p = 0,014) et un nombre eleve de lignes de biotherapies anterieures (OR = 0,57, IC95 % 0,36-0,92, p = 0,021) etaient significativement associes a une moindre survenue de MICI-DN. L’association avec une SI-IRM tendait a la significativite (OR= 0,62, IC95 % 0,38-1,02, p = 0,059). Conclusion Dans cette etude nationale de vraie vie, la survenue d’une MICI-DN sous anti-IL 17 est rare, avec une incidence faible, proche de celle rapportee dans la litterature pour des patients atteints de spondyloarthrite et non traites par anti-IL 17 (0,2 %) [1] . De plus cette incidence annuelle diminue regulierement de 2016 a 2019. Dans l’etude cas-temoins, la presence d’un antecedent de traitement par ETN peut etre un facteur confondant (ETN prescrit souvent chez des pts pour lesquels une MICI associee a ete eliminee).

Explicit numerical finite difference schemes for partial differential equations are well known to be easy to implement but they are particularly problematic for solving equations whose solutions admit shocks, blowups and discontinuities. Here we present an explicit numerical scheme for solving non-linear advection-diffusion equations admitting shock solutions that is both easy to implement and stable. The numerical scheme is obtained by considering the continuum limit of a discrete time and space stochastic process for non-linear advection-diffusion. The stochastic process is well posed and this guarantees the stability of the scheme. Several examples are provided to highlight the importance of the formulation of the stochastic process in obtaining a stable and accurate numerical scheme.

The experiment was carried out at Federal College of Forestry Jos, in Jos North Local Government Area of Plateau State to determine the phytotoxicity of cypermethrin pesticide on seed germination, growth and yield parameters of cowpea. Cypermethrin is popularly used by farmers as a means of treating seeds before planting to prevent insect, pest and birds attack. Randomized Complete Block Design (RCBD) involving 5 treatments T0 as control (No cypermethrin used), T1 with 0.25% cypermethrin (0.25ml of cypermethrin in 99.75ml of water), T2 with 0.50% cypermethrin (0.50ml of cypermethrin in 99.50ml of water), T3 with 0.75% cypermethrin (0.75ml of cypermethrin in 99.25ml of water) and T4 contained 1.00% cypermethrin (1.0ml of cypermethrin in 99.00ml water). Data was collected on radicle length, plumule length, number of leaves, number of branches, stem girth, number of seeds/pod, 100 seed weight, pod length and dry matter. Data collected was subjected to analysis of variance (ANOVA) at 5% level of significance using SPSS 23 and where significance was declared, Duncan Multiple Range Test (DMRT) was used to separate the means. The result of the research indicates that significance difference occurs in the radicle length (P

We derive the generalized master equations for a stochastic process representing populations entering, leaving, or waiting in compartments at discrete times. This discrete time compartment model limits to a fractional order continuous time compartment model for a particular choice of waiting time distribution and the appropriate limiting process. We demonstrate that the discrete time master equations can be used to provide an explicit numerical method that can be employed for solving the fractional order compartment equations. The advantage of this approach is that the numerical scheme has a physical interpretation, it is stable, and it is easy to implement. The method can be applied to a wide class of fractional order compartment model equations that arise in a broad range of applications.

There has been considerable recent interest in certain integral transform operators with non-singular kernels and their ability to be considered as fractional derivatives. Two such operators are the Caputo&ndash, Fabrizio operator and the Atangana&ndash, Baleanu operator. Here we present solutions to simple initial value problems involving these two operators and show that, apart from some special cases, the solutions have an intrinsic discontinuity at the origin. The intrinsic nature of the discontinuity in the solution raises concerns about using such operators in modelling. Solutions to initial value problems involving the traditional Caputo operator, which has a singularity inits kernel, do not have these intrinsic discontinuities.

A standard reaction–diffusion equation consists of two additive terms, a diffusion term and a reaction rate term. The latter term is obtained directly from a reaction rate equation which is itself derived from known reaction kinetics, together with modelling assumptions such as the law of mass action for well-mixed systems. In formulating a reaction–subdiffusion equation, it is not sufficient to know the reaction rate equation. It is also necessary to know details of the reaction kinetics, even in well-mixed systems where reactions are not diffusion limited. This is because, at a fundamental level, birth and death processes need to be dealt with differently in subdiffusive environments. While there has been some discussion of this in the published literature, few examples have been provided, and there are still very many papers being published with Caputo fractional time derivatives simply replacing first order time derivatives in reaction–diffusion equations. In this paper, we formulate clear examples of reaction–subdiffusion systems, based on, equal birth and death rate dynamics, Fisher–Kolmogorov, Petrovsky and Piskunov (Fisher–KPP) equation dynamics, and Fitzhugh–Nagumo equation dynamics. These examples illustrate how to incorporate considerations of reaction kinetics into fractional reaction–diffusion equations. We also show how the dynamics of a system with birth rates and death rates cancelling, in an otherwise subdiffusive environment, are governed by a mass-conserving tempered time fractional diffusion equation that is subdiffusive for short times but standard diffusion for long times.

Purpose Helical Tomotherapy (HT) appears as a valuable technique for total body irradiation (TBI) to create highly homogeneous and conformal dose distributions with more precise repositioning than conventional TBI techniques. The aim of this work is to describe the technique implementation, including treatment preparation, planning and dosimetric monitoring of TBI delivered in our institution from October 2016 to March 2019. Material and method Prior to patient care, irradiation protocol was set up using physical phantoms. Gafchromic films were used to assess dose distribution homogeneity and evaluate imprecise patient positioning impact. Sixteen patients’ irradiations with a prescribed dose of 12 Gy were delivered in 6 fractions of 2 Gy over 3 days. Pre-treatment quality assurance (QA) was performed for the verification of dose distributions at selected positions. In addition, in-vivo dosimetry was carried out using optically stimulated luminescence dosimeters (OSLD). Results Planning evaluation, as well as results of pre-treatment verifications, are presented. In-vivo dosimetry showed the strong consistency of OSLD measured doses. OSLD mean relative dose differences between measurement and calculation were respectively +0,96% and −2% for armpit and hands locations, suggesting better reliability for armpit OSLD positioning. Repercussion of both longitudinal and transversal positioning inaccuracies on phantoms is depicted up to 2 cm shifts. Conclusion The full methodology to set up TBI protocol, as well as dosimetric evaluation and pre-treatment QA, were presented. Our investigations reveal strong correspondence between planned and delivered doses shedding light on the dose reliability of OSLD for HT based TBI in-vivo dosimetry.

A generalised advection equation with a time fractional derivative is derived from a continuous time random walk on a one-dimensional lattice, with power law distributed waiting times. We consider walks governed by a two-sided jump density and walks governed by a one-sided jump density. With the two-sided density, the particle can jump in both directions on the lattice, whereas with the one-sided density the particle cannot jump in one of these directions. The master equations describing the evolution of the probability density for the position of the particle are different for each of the jump densities. However in an advective limit both master equations limit to a common generalized advection equation with time fractional derivatives. We have also considered the stochastic processes in a discrete time setting, again arriving at different discrete time master equations for each of the jump densities. The discrete time master equations can be used to provide different numerical approximations to the solutions of the fractional generalized advection equation. The approximations allow us to compare the efficacy of the one-sided and two-sided densities.

In the standard continuous time random walk the initial state is taken as a non-equilibrium state, in which the random walking particle has just arrived at a given site. Here we consider generalizations of the continuous time random walk to accommodate arbitrary initial states. One such generalization provides information about the initial state through the introduction of a first waiting time density that is taken to be different from subsequent waiting time densities. Another generalization provides information about the initial state through the prior history of the arrival flux density. The master equations have been derived for each of these generalizations. They are different in general but they are shown to limit to the same master equation in the case of an equilibrium initial state. Under appropriate conditions they also reduce to the master equation for the standard continuous time random walk with the non-equilibrium initial state.The diffusion limit of the generalized master equations is also considered, with Mittag-Leffler waiting time densities, resulting in the same fractional FokkerPlanck equation for different initial conditions.

Here we present a numerical method for the solution of time fractional partial differential equations (fPDEs). The method is based on constructing a sequence of integrable approximations to the fPDE, such that in the appropriate limit the original fractional PDE is obtained. Convergence results are obtained in general and examples are given for simple cases such as the fractional heat equation and the fractional diffusion-wave equation.

Introduction Lors de l’evaluation de la densite minerale osseuse (DMO) basee sur l’absorptiometrie biphotonique a rayons X (DXA), la decouverte d’une hyperdensite osseuse est inhabituelle. La frequence et les etiologies des hyperdensites osseuses restent largement meconnues. L’objectif de cette etude multicentrique etait d’evaluer la frequence et les etiologies des hyperdensites osseuses parmi des patients adultes ayant beneficie d’une mesure de la DMO sur une periode de 10 ans. Patients et methodes Il s’agit d’une etude observationnelle, retrospective et multicentrique, portant sur l’ensemble des patients ≥ 18 ans ayant beneficie d’une DMO par DXA sur une machine Hologic® entre avril 2008 et avril 2018 dans 6 centres de reference des pathologies osseuses. L’hyperdensite osseuse etait definie par un Z-score ≥ +4 sur au moins 1 site de mesure (rachis lombaire, col femoral, hanche totale). Les donnees ont ete reinterpretees selon les courbes de reference, a la hanche NHANES pour les 2 sexes, au rachis IOG pour les femmes et BMDCS pour les hommes. Les frequences des hyperdensites osseuses et des differentes etiologies ont ete estimees avec un intervalle de confiance a 95 % (methode exacte de Clopper-Pearson, intervalle asymetrique). Resultats Parmi les 72 225 patients ayant eu une DXA, 909 avaient un Z-score ≥ + 4 sur au moins l’un des sites de mesure, soit une frequence de 1,26 % [1,18 %-1,34 %]. Une hyperdensite osseuse etait plus frequemment retrouvee chez les hommes : 1,83 % [1,63 %-2,04 %]) que chez les femmes : 1,08 % [0,99 %-1,17 %]), p Conclusion Dans cette premiere etude multicentrique Francaise ayant porte sur plus de 72 000 patients, la prevalence de l’hyperdensite osseuse est de l’ordre de 1 % environ dont 80 % de causes artefactuelles essentiellement arthrosiques, suivies par les causes acquises locales et generalisees (osteodystrophies renales, myelofibroses, hypoparathyroidie…) et quelques rares causes genetiques.

Reaction-diffusion equations are widely used as the governing evolution equations for modeling many physical, chemical, and biological processes. Here we derive reaction-diffusion equations to model transport with reactions on a one-dimensional domain that is evolving. The model equations, which have been derived from generalized continuous time random walks, can incorporate complexities such as subdiffusive transport and inhomogeneous domain stretching and shrinking. A method for constructing analytic expressions for short time moments of the position of the particles is developed and moments calculated from this approach are shown to compare favourably with results from random walk simulations and numerical integration of the reaction transport equation. The results show the important role played by the initial condition. In particular, it strongly affects the time dependence of the moments in the short time regime by introducing additional drift and diffusion terms. We also discuss how our reaction transport equation could be applied to study the spreading of a population on an evolving interface., 38 pages, 10 figures