Directed Chaotic Transport in Hamiltonian Ratchets

We present a comprehensive account of directed transport in one-dimensional Hamiltonian systems with spatial and temporal periodicity. They can be considered as Hamiltonian ratchets in the sense that ensembles of particles can show directed ballistic transport in the absence of an average force. We discuss general conditions for such directed transport, like a mixed classical phase space, and elucidate a sum rule that relates the contributions of different phase-space components to transport with each other. We show that regular ratchet transport can be directed against an external potential gradient while chaotic ballistic transport is restricted to unbiased systems. For quantized Hamiltonian ratchets we study transport in terms of the evolution of wave packets and derive a semiclassical expression for the distribution of level velocities which encode the quantum transport in the Floquet band spectra. We discuss the role of dynamical tunneling between transporting islands and the chaotic sea and the breakdown of transport in quantum ratchets with broken spatial periodicity.Comment: 22 page

Self-assessment of quality of life and aging of Alzheimer development risk adults

ABSTRACT: middle-age adult carriers and non-carriers of mutation E280A in gene Presenilin 1 for Early Onset Familial Alzheimer’s Disease and of elderly adults in Antioquia-Colombia. Study conducted from January 2005 to June 2007. Methodology: descriptive transversal study in which 162 asymptomatic people at risk of developing Alzheimer’s disease as a genetic consequence or as a consequence of the process of aging. They were subdivided into three groups: 27 carriers of the mutation, 39 non-carriers and 96 elderly adults. The study was conducted at the Neuroscience Group in Medellín (Antioquia) and at a gerontology center in Envigado (Antioquia) named Atardecer. Social-demographic characteristics were analyzed and quality of life and overall aging selfassessment tests were applied, which included the World Health Organization Quality of Life, and the Nürnberg -Self-Evaluation-List respectively. Statistic Analysis: The groups were described and they were compared to the variables of the study using Kruskall Wallis non-parametric ANOVA and Mann-Whitney’s U-test. Results: the mean scores of the instruments to assess quality of life and overall aging of three groups of participants were above 50 points and below 55 points respectively. Conclusions: elderly adults assessed themselves as having a lower quality of life than carriers and non-carriers, especially in the physical health area, and in their perception of aging, in spite of carriers’ conditions, although in general the scores were good in all the groups.RESUMEN: Describir la autovaloración de calidad de vida y del envejecimiento de tres grupos: adultos portadores y no portadores de la mutación E280A en el gen de la Presenilina 1 para Enfermedad de Alzheimer Familiar Precoz, y adultos mayores, en Antioquia-Colombia, estudio realizado entre enero de 2005 y junio de 2007. Metodología: estudio descriptivo transversal donde participaron 162 personas asintomáticas en riesgo de desarrollar Enfermedad de Alzheimer como consecuencia genética o del proceso de envejecimiento, quienes se subdividieron en tres grupos: 27 portadores, 39 no portadores y 96 adultos mayores. Investigación realizada en el Grupo de Neurociencias de la Universidad de Antioquia (Medellín) y en el Centro Gerontológico Atardecer (Envigado). Se analizaron las características sociodemográficas, y se aplicaron pruebas para la autovaloración de la calidad de vida global del envejecimiento: World Health Organization Quality of Life y la Nürnberg -Self-Evaluation-List respectivamente. Análisis estadístico: Se describieron los grupos y se compararon frente a las variables de estudio utilizando el análisis de varianza no paramétrico de Kruskall Wallis y la prueba U de Mann-Whitney. Resultados: las calificaciones medias de los instrumentos para la autovaloración de calidad de vida y global del envejecimiento en los tres grupos de participantes, fueron superiores a 50 puntos e inferiores a 55 puntos respectivamente. Conclusiones: los adultos mayores se autovaloran con menor calidad de vida que los portadores y los no portadores, especialmente en el área de salud física, al igual que en la percepción del envejecimiento, a pesar de las condiciones de los portadores, aunque, en general, todos los grupos las puntuaron bien

A Spontaneous Mutation of the Rat Themis Gene Leads to Impaired Function of Regulatory T Cells Linked to Inflammatory Bowel Disease

Spontaneous or chemically induced germline mutations, which lead to Mendelian phenotypes, are powerful tools to discover new genes and their functions. Here, we report an autosomal recessive mutation that occurred spontaneously in a Brown-Norway (BN) rat colony and was identified as causing marked T cell lymphopenia. This mutation was stabilized in a new rat strain, named BNm for “BN mutated.” In BNm rats, we found that the T cell lymphopenia originated in the thymus, was intrinsic to CD4 T lymphocytes, and was associated with the development of an inflammatory bowel disease. Furthermore, we demonstrate that the suppressive activity of both peripheral and thymic CD4+ CD25bright regulatory T cells (Treg) is defective in BNm rats. Complementation of mutant animals with BN Treg decreases disease incidence and severity, thus suggesting that the impaired Treg function is involved in the development of inflammatory bowel disease in BNm rats. Moreover, the cytokine profile of effector CD4 T cells is skewed toward Th2 and Th17 phenotypes in BNm rats. Linkage analysis and genetic dissection of the CD4 T cell lymphopenia in rats issued from BNm×DA crosses allowed the localization of the mutation on chromosome 1, within a 1.5 megabase interval. Gene expression and sequencing studies identified a frameshift mutation caused by a four-nucleotide insertion in the Themis gene, leading to its disruption. This result is the first to link Themis to the suppressive function of Treg and to suggest that, in Themis-deficient animals, defect of this function is involved in intestinal inflammation. Thus, this study highlights the importance of Themis as a new target gene that could participate in the pathogenesis of immune diseases characterized by chronic inflammation resulting from a defect in the Treg compartment

Harmonizing methods for wildlife abundance estimation and pathogen detection in Europe-a questionnaire survey on three selected host-pathogen combinations

__Background:__ The need for wildlife health surveillance as part of disease control in wildlife, domestic animals and humans on the global level is widely recognized. However, the objectives, methods and intensity of existing wildlife health surveillance programs vary greatly among European countries, resulting in a patchwork of data that are difficult to merge and compare. This survey aimed at evaluating the need and potential for data harmonization in wildlife health in Europe. The specific objective was to collect information on methods currently used to estimate host abundance and pathogen prevalence. Questionnaires were designed t

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk