Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis

Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis, organ failure(s), and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT) or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4%, and worsened in 20.4%. The 28-day transplant-free mortality was low-to-moderate (6%-18%) in patients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥12 mg/dL) at ACLF diagnosis. Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short- (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3-7 days, and did not undergo LT, mortality was 100% by 28 days. CONCLUSIONS Assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility.

Metabolic syndrome and cardiovascular mortality among participants of the hypertension detection and follow-up program

Metabolic Syndrome (MetS) is a clustering of cardiovascular (CV) risk factors that includes obesity, dyslipidemia, hyperglycemia, and elevated blood pressure. Applying the criteria for MetS can serve as a clinically feasible tool for identifying patients at high risk for CV morbidity and mortality, particularly those who do not fall into traditional risk categories. The objective of this study was to examine the association between MetS and CV mortality among 10,940 American hypertensive adults, ages 30-69 years, participating in a large randomized controlled trial of hypertension treatment (HDFP 1973-1983). MetS was defined as the presence of hypertension and at least two of the following risk factors: obesity, dyslipidemia, or hyperglycemia. Of the 10,763 individuals with sufficient data available for analysis, 33.2% met criteria for MetS at baseline. The baseline prevalence of MetS was significantly higher among women (46%) than men (22%) and among non-blacks (37%) versus blacks (30%). All-cause and CV mortality was assessed for 10,763 individuals. Over a median follow-up of 7.8 years, 1,425 deaths were observed. Approximately 53% of these deaths were attributed to CV causes. Compared to individuals without MetS at baseline, those with MetS had higher rates of all-cause mortality (14.5% v. 12.6%) and CV mortality (8.2% versus 6.4%). The unadjusted risk of CV mortality among those with MetS was 1.31 (95% confidence interval [CI], 1.12-1.52) times that for those without MetS at baseline. After multiple adjustment for traditional risk factors of age, race, gender, history of cardiovascular disease (CVD), and smoking status, individuals with MetS, compared to those without MetS, were 1.42 (95% CI, 1.20-1.67) times more likely to die of CV causes. Of the individual components of MetS, hyperglycemia/diabetes conferred the strongest risk of CV mortality (OR 1.73; 95% CI, 1.39-2.15). Results of the present study suggest MetS defined as the presence of hypertension and 2 additional cardiometabolic risk factors (obesity, dyslipidemia, or hyperglycemia/diabetes) can be used with some success to predict CV mortality in middle-aged hypertensive adults. Ongoing and future prospective studies are vital to examine the association between MetS and cardiovascular morbidity and mortality in select high-risk subpopulations, and to continue evaluating the public health impact of aggressive, targeted screening, prevention, and treatment efforts to prevent future cardiovascular disability and death.^

Influence of sediment acidification and water flow on sediment acceptance and dispersal of juvenile soft-shell clams (Mya arenaria L.)

Although ocean acidification is expected to reduce carbonate saturation and yield negative impacts on open-ocean calcifying organisms in the near future, acidification in coastal ecosystems may already be affecting these organisms. Few studies have addressed the effects of sedimentary saturation state on benthic invertebrates. Here, we investigate whether sedimentary aragonite saturation (Omega aragonite) and proton concentration ([H+]) affect burrowing and dispersal rates of juvenile soft-shell clams (Mya arenaria) in a laboratory flume experiment. Two size classes of juvenile clams (0.5-1.5 mm and 1.51-2.5 mm) were subjected to a range of sediment Omega aragonite and [H+] conditions within the range of typical estuarine sediments (Omega aragonite 0.21-1.87; pH 6.8-7.8; [H+] 1.58 × 10**-8-1.51 × 10**- 7) by the addition of varying amounts of CO2, while overlying water pH was kept constant ~ 7.8 (Omega aragonite ~ 1.97). There was a significant positive relationship between the percent of juvenile clams burrowed in still water and Omega aragonite and a significant negative relationship between burrowing and [H+]. Clams were subsequently exposed to one of two different flow conditions (flume; 11 cm/s and 23 cm/s) and there was a significant negative relationship between Omega aragonite and dispersal, regardless of clam size class and flow speed. No apparent relationship was evident between dispersal and [H+]. The results of this study suggest that sediment acidification may play an important role in soft-shell clam recruitment and dispersal. When assessing the impacts of open-ocean and coastal acidification on infaunal organisms, future studies should address the effects of sediment acidification to adequately understand how calcifying organisms may be affected by shifting pH conditions.

Separation of Control and Cash-Flow Rights of State Owned Listed Enterprises: Channels of Expropriation after the Discriminated Share Reform in China

Literature on agency problems arising between controlling and minority owners claim that separation of cash flow and control rights allows controllers to expropriate listed firms, and further that separation emerges when dual class shares or pyramiding corporate structures exist. Dual class share and pyramiding coexisted in listed companies of China until discriminated share reform was implemented in 2005. This paper presents a model of controller to expropriate behavior as well as empirical tests of expropriation via particular accounting items and pyramiding generated expropriation. Results show that expropriation is apparent for state controlled listed companies. While reforms have weakened the power to expropriate, separation remains and still generates expropriation. Size of expropriation is estimated to be 7 to 8 per cent of total asset at mean. If the "one share, one vote" principle were to be realized, asset inflation could be reduced by 13 percent.

Lithogeochemistry and fluid flow in the epithermal Veta Rublo base metal-silver deposit, Chonta Mine (Huancavelica, Perú)

The Chonta Mine (75º00’30” W & 13º04’30”S, 4495 to 5000 m absl), owned by Compañía Minera Caudalosa, operates a polymetallic Zn-Pb-Cu-Ag vein system of the low sulphidation epithermal type, hosted by cenozoic volcanics of dacitic to andesitic composition (Domos de Lava Formation). Veta Rublo, one of the main veins of the system, is worked underground to nearly 300 m. It strikes 60-80º NE and dips 60-70º SE; its width varies between 0.30 and 2.20m, and it crops out along 1 km, but is continued along strike by other veins, as Veta Caudalosa, for some 5 km. Typical metal contents are 7% Zn, 5% Pb, 0.4% Cu and 3 oz/t Ag, with quartz, sericite, sphalerite, galena, pyrite, chalcopyrite, fahlore as main minerals, and minor carbonate and sulphosalts.

Geothermometry, ore geochemistry and fluid flow in the Esperanza Vein, Huachocolpa District (Huancavelica, Peru)

The Esperanza Zn-Pb-Ag vein, owned by Compañía de Minas Buenaventura S.A.A., lies over 4000 to 4650 masl in the Western Cordillera of the Peruvian Central Andes. The Esperanza low sulphidation epithermal vein trends ~E-W along 1500 m; it dips to the South and can be followed to 350 m depth. As other veins of the district, like Teresita and Bienaventurada, it is hosted by intermediate to felsic volcanics (andesitic to dacitic compositions) of the Huachocolpa Group (Middle Miocene to Upper Pliocene). The mineralisation occurs mostly as open space filling related to fracture development during the Quechua III deformational event. Main ore minerals are sphalerite, galena, tetrahedrite, pyrite, chalcopyrite and Ag and Pb sulfosalts; quartz, barite and calcite are the main gangue minerals. Current production grades are ~5% Zn, ~8Oz/t Ag, ~3% Pb; usually very low Cu (mean ~0.04%).

Effects of diet and exercise on metabolic syndrome and the underlying factors = Efectos de la dieta y el ejercicio sobre el síndrome metabólico y sus factores

Introducción. El número de personas que padecen síndrome metabólico ha incrementado a nivel mundial durante las últimas dos décadas. Existen numerosos estudios que tratan de comparar prevalencias según los diferentes criterios y estimaciones del riesgo metabólico. De ellos se puede concluir que el principal hallazgo ha sido recalcar la necesidad de una definición estándar universal. A pesar de estas discrepancias no hay lugar a duda sobre el problema de salud pública que esto conlleva. Se necesitan medidas y estrategias urgentes para prevenir y controlar esta emergente epidemia global y para ello se debe prestar especial atención a los cambios en el estilo de vida, fundamentalmente dieta y ejercicio. A pesar de todo, existe a día de hoy una importante controversia sobre el tipo de ejercicio más efectivo y su combinación con la dieta para conseguir mejoras en la salud. Objetivos. Estudiar los índices de riesgo metabólico empleados en la literatura científica y las terapias basadas en dieta y ejercicio para el tratamiento de los factores del síndrome metabólico en adultos con sobrepeso. Diseño de investigación. Los datos empleados en el análisis de esta tesis son, primeramente un estudio piloto, y posteriormente parte del estudio “Programas de Nutrición y Actividad Física para el tratamiento de la obesidad” (PRONAF). El estudio PRONAF es un proyecto consistente en un estudio clínico sobre programas de nutrición y actividad física para el sobrepeso y la obesidad, desarrollado en España durante varios años de intervenciones. Fue diseñado, en parte, para tratar de comparar protocolos de entrenamiento de resistencia, cargas y combinado en igualdad de volumen e intensidad, con el objetivo de evaluar su impacto en los factores de riesgo y la prevalencia del síndrome metabólico en personas con sobrepeso y obesidad. El diseño experimental es un control aleatorio y el protocolo incluye 3 modos de ejercicio (entrenamiento de resistencia, con cargas y combinado) y restricción dietética sobre diversas variables determinantes del estado de salud. Las principales variables para la investigación que comprende esta tesis fueron: actividad física habitual, marcadores de grasa corporal, niveles de insulina, glucosa, triglicéridos, colesterol total, colesterol HDL, colesterol LDL, presión arterial y parámetros relacionados con el ejercicio. Conclusiones. A) Los índices de riesgo metabólico estudiados presentan resultados contradictorios en relación al riesgo metabólico en un individuo, dependiendo de los métodos matemáticos empleados para el cálculo y de las variables introducidas, tanto en mujeres sanas como en adultos en sobrepeso. B) El protocolo de entrenamiento combinado (de cargas y de resistencia) junto con la dieta equilibrada propuesto en este estudio fue la mejor estrategia para la mejora del riesgo de síndrome metabólico en adultos con sobrepeso. C) Los protocolos de entrenamiento supervisado de resistencia, con cargas y combinado junto con la restricción nutricional, no obtuvieron mejoras sobre el perfil lipídico, más allá de los cambios conseguidos con el protocolo de dieta y recomendaciones generales de actividad física habitual en clínica, en adultos con sobrepeso. Background. Over the past two decades, a striking increase in the number of people with the MetS worldwide has taken place. Many studies compare prevalences using different criteria and metabolic risk estimation formulas, and perhaps their main achievement is to reinforce the need for a standardized international definition. Although these discrepancies, there is no doubt it is a public health problem. There is urgent need for strategies to prevent and manage the emerging global epidemic, special consideration should be given to behavioral and lifestyle, mainly diet and exercise. However, there is still controversy about the most effective type of exercise and diet combination to achieve improvements. Objectives. To study the metabolic risk scores used in the literature and the diet and exercise therapies for the treatment of the MetS factors in overweight adults. Research design. The data used in the analysis was collected firstly in a pilot study and lately, as a part of the “Programas de Nutrición y Actividad física para el tratamiento de la obesidad” study (PRONAF). The PRONAF Study is a clinical research project in nutrition and physical activity programs for overweight and obesity, carried out in Spain (2008-2011). Was designed, in part, to attempt to match the volume and intensity of endurance, strength and combined training protocols in order to evaluate their impact on risk factors and MetS prevalence in overweight and obese people. The design and protocol included three exercise modes (endurance, strength and combined training) and diet restriction, in a randomized controlled trial concerning diverse health status variables. The main variables under investigation were habitual physical activity, markers of body fat, fasting serum levels of insulin, glucose, triglycerides, total, LDL and HDL cholesterol, blood pressure and diet and exercise parameters. Main outcomes. A) The metabolic risk scores studied presented contradictory results in relation to the metabolic risk of an individual, depending on the mathematical method used and the variables included, both in healthy women and overweight adults. B) The protocol proposed for combination of strength and endurance training combined with a balance diet was the optimal strategy for the improvement of MetS risk in overweight adults. C) The intervention program of endurance, strength or combined supervised training protocol with diet restriction did not achieved further improvements in lipid profile than a habitual clinical practice protocol including dietary advice and standard physical activity recommendations, in overweight adults.

Influence of gravity on heavy particle statistics in turbulent channel and pipe flow at matched Kàrmàn number

In this work, we use large eddy simulations (LES) and Lagrangian tracking to study the influence of gravity on particle statistics in a fully developed turbulent upward/downward flow in a vertical channel and pipe at matched Kàrmàn number. Only drag and gravity are considered in the equation of motion for solid particles, which are assumed to have no influence on the flow field. Particle interactions with the wall are fully elastic. Our findings obtained from the particle statistics confirm that: (i) the gravity seems to modify both the quantitative and qualitative behavior of the particle distribution and statistics of the particle velocity in wall normal direction; (ii) however, only the quantitative behavior of velocity particle in streamwise direction and the root mean square of velocity components is modified; (iii) the statistics of fluid and particles coincide very well near the wall in channel and pipe flow with equal Kàrmàn number; (iv) pipe curvature seems to have quantitative and qualitative influence on the particle velocity and on the particle concentration in wall normal direction.

Aeroacoustic noise prediction in high speed trains due to attached and detached flow

This paper aims to set out the influence of the flow field around high speed trains in open field. To achieve this parametric analysis of the sound pressure inside the train was performed. Three vibroacoustic models of a characteristic train section are used to predict the noise inside the train in open field by using finite element method FEM, boundary element method (BEM) and statistical energy analysis (SEA) depending on the frequency range of analysis. The turbulent boundary layer excitation is implemented as the only airborne noise source, in order to focus on the study of the attached and detached flow in the surface of the train. The power spectral densities of the pressure fluctuation in the train surface proposed by [Cockburn and Roberson 1974, Rennison et al. 2009] are applied on the exterior surface of the structural subsystems in the vibroacoustic models. An increase in the sound pressure level up to10 dB can be appreciated due to the detachment of the flow around the train. These results highlight the importance to determine the detached regions prediction, making critical the airborne noise due to turbulent boundary layer.

Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: A dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia

Severe jaundice leading to kernicterus or death in the newborn is the most devastating consequence of glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G-6-PD) deficiency. We asked whether the TA repeat promoter polymorphism in the gene for uridinediphosphoglucuronate glucuronosyltransferase 1 (EC 2.4.1.17; UDPGT1), associated with benign jaundice in adults (Gilbert syndrome), increases the incidence of neonatal hyperbilirubinemia in G-6-PD deficiency. DNA from term neonates was analyzed for UDPGT1 polymorphism (normal homozygotes, heterozygotes, variant homozygotes), and for G-6-PD Mediterranean deficiency. The variant UDPGT1 promoter allele frequency was similar in G-6-PD-deficient and normal neonates. Thirty (22.9%) G-6-PD deficient neonates developed serum total bilirubin ≥ 257 μmol/liter, vs. 22 (9.2%) normals (P = 0.0005). Of those with the normal homozygous UDPGT1 genotype, the incidence of hyperbilirubinemia was similar in G-6-PD-deficients and controls (9.7% and 9.9%). In contrast, in the G-6-PD-deficient neonates, those with the heterozygous or homozygous variant UDPGT1 genotype had a higher incidence of hyperbilirubinemia than corresponding controls (heterozygotes: 31.6% vs. 6.7%, P < 0.0001; variant homozygotes: 50% vs. 14.7%, P = 0.02). Among G-6-PD-deficient infants the incidence of hyperbilirubinemia was greater in those with the heterozygous (31.6%, P = 0.006) or variant homozygous (50%, P = 0.003) UDPGT1 genotype than in normal homozygotes. In contrast, among those normal for G-6-PD, the UDPGT1 polymorphism had no significant effect (heterozygotes: 6.7%; variant homozygotes: 14.7%). Thus, neither G-6-PD deficiency nor the variant UDPGT1 promoter, alone, increased the incidence of hyperbilirubinemia, but both in combination did. This gene interaction may serve as a paradigm of the interaction of benign genetic polymorphisms in the causation of disease.

Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly

At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human PEX19 cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (Pex19p) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated Pex19p is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal Pex19p. These results demonstrate that PEX19 is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of Pex19p. Moreover, Pex19p is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.