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Although the deep-rooted, institutional issues of redlining, mass incarceration, and food apartheid in the West Side of Chicago are each loaded enough to warrant their own documentaries, Brett A. Schwartz's [...]

After a feasibility study, Repsol YPF decided to apply a model-based predictive controller to a batch reactor producing polyols. The predictive controller for reactors (PCR) is a set of control [...]

Objectives:Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.Methods:386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure.Results:Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death.Conclusions:A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

In the procedure to monitor a new batch using the method proposed by Nomikos and MacGregor [AIChE J. 1994, 40 (8), 1361−1375], an assumption about the unknown future samples in the batch has to be taken. This work demonstrates that using the missing data option and solving the score estimation problem with an appropriate method are equivalent to the use of an accurate adaptive forecast model for the future samples over the shrinking horizon of the remainder of the batch. The dynamic properties of the principal component analysis (PCA) model are illustrated by re-expressing the projection model as a time-varying multivariate prediction model. The benefits of using the missing data estimation option are analyzed by contrasting it with other options on the basis of (i) the accuracy of the forecast done for the unknown samples, (ii) the quality of the score estimates, and (iii) the detection performance during monitoring. Because of the tremendous structural information built into these multivariate PCA models for batch processes, the missing data option is shown to yield the best performance by all measures in predicting the future unknown part of the trajectory, even from the beginning of the batch. However, for the purpose of online detection of process faults (in process monitoring), the differences among the trajectory estimation methods appear to be much less critical because the control charts used in each case are tailored to the filling-in mechanism employed. All of the approaches appear to provide powerful charting methods for monitoring the progress of batch processes.

Multivariate statistical methods are used to analyze data from an industrial batch drying process. The objective of the study was to uncover possible reasons for major problems occurring in the quality of the product produced in the process. Partial least-squares (PLS) methods were able to isolate which group of variables in the chemistry, in the timing of the various stages of the batch, and in the shape of the time-varying trajectories of the process variables were related to a poor-quality product. The industrial study illustrates the approach and the power of these multivariate methods for troubleshooting problems occurring in complex batch processes. Several new variations in the multivariate PLS methodology for the analysis of batch data are also implemented. In particular, an application utilizing a novel approach to the time warping of the trajectories for batches, and the subsequent use of the time-warping information, is presented. The use of the time history of the PLS weights of the process variable trajectories to diagnose problems in the dynamic operation of the batches is also clearly illustrated, as is the use of contribution plots for finding features which distinguished between the operating histories of good and bad batches.

Twenty-one Trypanosoma cruzistocks isolated from Triatoma infestansand humans of the Chilean Andean highlands were studied at the genotypic level by schizodeme and molecular karyotype analyses, which allowed a clear distinction of the parasites from those hosts. A phenotypical characterization was performed by proteolytic activity after electrophoretic fractionation without discrimination among the stocks. Metacyclic trypomastigotes obtained in vitroproved to be infective to Swiss mice and the study of immune response and biological behavior was assessed. Of a total of 21 T. cruzistocks, only 11 proved to be infective in mice due to difficulties in obtaining metacyclic trypomastigotes with the parasite populations isolated from humans. Western blot analysis revealed a complex immune response even in the first days postinfection with each T. cruzistrain studied. Antigenic recognition by each immune serum is characteristic, although several major and common antigens were detected. Lytic antibodies were studied by the in vitrocomplement-mediated lytic assay using purified metacyclic trypomastigotes as target cells. All the T. cruziisolates tested induced lytic antibodies in this experimental model. Parasitemias were moderate and characteristic for each T. cruzistrain. Results are compared with metacyclic forms of the infective and pathogenic Tulahuen strain.

Forty-one Trypanosoma cruzi stocks isolated from the Chilean vectors Triatoma infestans and Triatoma spinolai were characterized by pulse-field gel electrophoresis and Southern blotting with the cruzipain gene, and by schizodeme analysis of kinetoplast DNA with EcoRI and Msp I. Seven parasite groups were found by molecular karyotype which correlate with schizodeme and multilocus enzyme electrophoresis, supporting the concept of clonal propagation for Trypanosoma cruzi. A predominant T. cruzi stock was isolated from domiciliary T. infestans in several geographical areas of Chile. In contrast, other frequently found genotypes were circulating in the sylvatic and domestic transmission cycles of specific geographical areas. The greatest heterogeneity of T. cruzi stocks was found among sylvatic T. spinolai where at least 4 genotypes were obtained from a sample of 16 T. cruzi stocks.

Abstract.: Background: To evaluate the clinical significance of the computed tomographic finding of subcapsular hepatic necrosis following liver transplantation. Methods: 105 computed tomography scans performed in 50 allografts, 6 days to 4 years following transplantation, were retrospectively reviewed and divided into two groups: those with and those without the computed tomographic finding of subcapsular hepatic necrosis. Extrahepatic fluid, biliary dilatation, circumcaval rings, periportal collar, biochemistry, and random biopsies were correlated with the computed tomographic finding of subcapsular hepatic necrosis. Results: Computed tomographic finding of subcapsular hepatic necrosis was demonstrated at some point in 21 (42%) patients and was never demonstrated in 29 (58%) patients. The association of periportal collar with the computed tomographic finding of subcapsular hepatic necrosis was significant; there was no significant association with other computed tomographic findings. There was no significant difference in serum transaminases between the two groups. There was no significant difference in necrosis on biopsy between the two groups; however, the association of acute cellular rejection with the computed tomographic finding of subcapsular hepatic necrosis was significant. Conclusions: Computed tomographic finding of subcapsular hepatic necrosis is a common finding following liver transplantation, which has little clinical prognostic significance.

The identification and cloning of the mitochondrial autoantigens in primary biliary cirrhosis (PBC) have provided new clues in disease pathogenesis. The two major autoantigens are the E2 subunits of pyruvate dehydrogenase and branched-chain ketoacid dehydrogenase (BCKD). Interestingly, one of these complexes, BCKD-E2, is already well known to clinical medicine based on its association with genetic mutations in maple syrup urine disease (MSUD). Patients with this disease have an inability to metabolize branched-chain amino acids. In the present study, we have taken advantage of the known sequence of BCKD-E2 from normal humans, and addressed the issue of whether there is an altered autoantigen sequence in hepatocytes of individuals with primary biliary cirrhosis. In particular, we examined both the leader sequence and the B-cell immunodominant epitope, the lipoic acid domain. In addition, because patients with PBC have autoantibodies to the BCKD-E2 complex, we have quantitated plasma levels of α-ketoacids potentially affected in maple syrup urine disease. These include pyruvic acid (PY), phenylpyruvic acid (PP), α-ketoisocaproic acid (KIC) α-ketoisovalerate (KIV) and α-keto-β-methylvaleric acid (KMV). The levels of these α-ketoacids were compared in patients with primary sclerosing cholangitis and normal volunteers. The sequence of BCKD-E2 obtained from PBC hepatocytes showed homology with normal BCKD. Further studies of autoantigen structure and sequence are clearly indicated, including those involved in mitochondrial transport and localization. Finally, we noted a statistically significant increase in all plasma α-ketoacids except α-keto-β-methylvaleric acid in PBC patients. The significance of this is unknown, but suggests that abnormalities in amino acid metabolism are secondary, not only to hepatic failure, but potentially to autoantibodies.

Intraperitoneal (i.p.) injection of peptidoglycan-polysaccharide derived from group A streptococci (PG-APS) causes chronic arthritis with spontaneous remissions and exacerbations. We hypothesized that, following i.p. injection, PG-APS released from hepatic stores mediated spontaneous recurrences of arthritis. We tested whether transplanted livers with large amounts of PG-APS were able to reactivate quiescent arthritis. Saline-loaded (group 1) or PG-APS-loaded (group 2) livers were transplanted into rats which had been injected intra-articularly 10 days earlier with PG-APS in one joint and saline in the other. A comparison was made with the arthritis that occurred in rats injected i.p. with PG-APS which did not receive transplants (group 3). Arthritis was monitored by serial measurement of joint diameters. Transplantation of saline-loaded livers (group 1) caused no reactivation of arthritis. However, transplantation of PG-APS-loaded livers (group 2) reactivated arthritis (P < 0.0001). Injection of PG-APS i.p. (group 3) induced the most-severe arthritis. PG-APS levels in plasma decreased with time, and PG-APS accumulated in the spleen in groups 2 and 3. Plasma and hepatic levels of PG-APS in rats injected i.p. with PG-APS were greater than levels in rats transplanted with PG-APS-loaded livers, which in turn were greater than levels in rats with saline-loaded livers. Plasma tumor necrosis factor did not correlate with recurrence of arthritis. Transplantation with PG-APS-loaded livers induced reactivation of arthritis in preinjured joints. The extent of arthritis was proportional to hepatic PG-APS content. Reactivation of arthritis may be mediated by slow release of liver-sequestered PG-APS or cytokines (not tumor necrosis factor) released by the liver.

The extraordinary specificity of bile duct destruction in primary biliary cirrhosis (PBC) and the presence of T cell infiltrates in the portal tracts have suggested that biliary epithelial cells are the targets of an autoimmune response. The immunodominant antimitochondrial response in patients with PBC is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). Hitherto, there have only been limited reports on the characterization and V beta usage of PDC-E2-specific cloned T cell lines. In this study, we examined peripheral blood mononuclear cells (PBMC) for their reactivity to the entire PDC complex as well as to the E1- and E2-specific components. We also examined the phenotype, lymphokine profile, and V beta usage of PDC-specific T cell clones isolated from cellular infiltrates from the livers of PBC patients. We report that PBMC from 16/19 patients with PBC, but not 12 control patients, respond to the PDC-E2 subunit. Interestingly, this response was directed to the inner and/or the outer lipoyl domains, despite the serologic observation that the autoantibody response is directed predominantly to the inner lipoyl domain. Additionally, lymphokine analysis of interleukin (IL) 2/IL-4/interferon gamma production from individual liver-derived autoantigen-specific T cell clones suggests that both T helper cell Th1- and Th2-like clones are present in the liver. Moreover, there was considerable heterogeneity in the T cell receptor for antigen (TCR) V beta usage of these antigen-specific autoreactive T cell clones. This is in contrast to murine studies in which animals are induced to develop autoimmunity by specific immunization and have an extremely limited T cell V beta repertoire. Thus, our data suggest that in human organ-specific autoimmune diseases, such as PBC, the TCR V beta repertoire is heterogenous.

Staphylococcus aureuscells suspended in a human immunoglobulin G (IgG) solution adsorbed nearly 90% of the IgG; electron micrographs showed the cells enclosed in a thick, dense envelope of IgG.

Profiles on the progress of spinal extradural anaesthesia were made in 246 patients using various concentrations of lignocaine, bupivacaine and etidocaine. The advance of analgesia through the different dermatomes showed a consistent and orderly spread on the upper lumbar and thoracic segments. This spread was irregular through the lower lumbar and upper sacral segments. The first sacral segment was especially difficult to block with an overall failure rate of 17.53% with presently available concentrations of various local anaesthetics. This failure was abolished with the use of etidocaine 1.5%. The presence of a delay or failure at the level of L5–S2 is probably related to the larger diameter of these nerve roots as ascertained from measurements in 11 cadavers.