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Background The availability of direct-acting antivirals (DAA) for the treatment of hepatitis C (HCV) has resulted in the ability to safely and effectively treat patients with cirrhosis and end-stage liver disease. However, information is limited with regard to the impact of DAA treatment on inpatient health-related resource utilization in patients with advanced HCV-related cirrhosis. We aimed to ascertain the impact of DAA treatment on the frequency of liver-related hospitalizations and associated costs in patients with cirrhosis. Patients and methods Retrospective cohort analysis carried out at a single US reference center that compared patients with HCV cirrhosis according to treatment status: the untreated group (January 2011 to December 2013) and the DAA-treated group (January 2014 to March 2017). The primary outcome was the difference in the incidence rate of liver-related hospitalizations. Secondary outcomes included differences in the incidence of hepatocellular carcinoma, liver transplant, and all-cause mortality. We calculated the projected savings per-patient treated per-year on the basis of calculated hospitalization rate stratified by Child-Turquotte-Pugh (CTP) score. Results Baseline characteristics were similar between the untreated (n=182) and DAA-treated (n=196) cohorts. Mean follow-up time in the untreated and treated cohort was 20.4 and 17.7 months, respectively. The incidence rates of liver-related hospitalizations were 29.1/100 and 10.4/100 person-years of follow-up (P≤0.0001) in the untreated and treated cohorts, respectively. This was accounted for by a decreased incidence of hospitalizations in patients with CTP-A (75.8%) and CTP-B (64.5%), but not CTP-C. Conclusion Successful DAA treatment reduces hospitalization rate and resource utilization costs in patients with CTP-A and CTP-B, but not in those with CTP-C.

Recent developments in genome sequencing combined with bioinformatic analysis have revealed that actinomycetes contain a plethora of unexpected BGCs and thus have the potential to produce many more natural products than previously thought. This reflects the inability to detect the production of these compounds under laboratory conditions, perhaps through the use of inappropriate growth media or the absence of the environmental cues required to elicit expression of the corresponding BGCs. One approach to overcoming this problem is to circumvent the regulatory mechanisms that control expression of the BGC in its natural host by deploying heterologous expression. The generally compact nature of lasso peptide BGCs makes them particularly amenable to this approach, and, in the example given here, analysis revealed a new member of the lasso peptide family of RiPPs. This approach should be readily applicable to other cryptic lasso peptide gene clusters and would also facilitate the design and production of nonnatural variants by changing the sequence encoding the core peptide, as has been achieved with other classes of RiPPs., Analysis of the genome sequence of Streptomyces leeuwenhoekii C34T identified biosynthetic gene clusters (BGCs) for three different lasso peptides (Lp1, Lp2, and Lp3) which were not known to be made by the strain. Lasso peptides represent relatively new members of the RiPP (ribosomally synthesized and posttranslationally modified peptides) family of natural products and have not been extensively studied. Lp3, whose production could be detected in culture supernatants from S. leeuwenhoekii C34T and after heterologous expression of its BGC in Streptomyces coelicolor, is identical to the previously characterized chaxapeptin. Lp1, whose production could not be detected or achieved heterologously, appears to be identical to a recently identified member of the citrulassin family of lasso peptides. Since production of Lp2 by S. leeuwenhoekii C34T was not observed, its BGC was also expressed in S. coelicolor. The lasso peptide was isolated and its structure confirmed by mass spectrometry and nuclear magnetic resonance analyses, revealing a novel structure that appears to represent a new family of lasso peptides. IMPORTANCE Recent developments in genome sequencing combined with bioinformatic analysis have revealed that actinomycetes contain a plethora of unexpected BGCs and thus have the potential to produce many more natural products than previously thought. This reflects the inability to detect the production of these compounds under laboratory conditions, perhaps through the use of inappropriate growth media or the absence of the environmental cues required to elicit expression of the corresponding BGCs. One approach to overcoming this problem is to circumvent the regulatory mechanisms that control expression of the BGC in its natural host by deploying heterologous expression. The generally compact nature of lasso peptide BGCs makes them particularly amenable to this approach, and, in the example given here, analysis revealed a new member of the lasso peptide family of RiPPs. This approach should be readily applicable to other cryptic lasso peptide gene clusters and would also facilitate the design and production of nonnatural variants by changing the sequence encoding the core peptide, as has been achieved with other classes of RiPPs.

In a pilot study, heavy water labeling was used to determine hepatitis B surface antigen (HBsAg) turnover rates in chronic hepatitis B (CHB) patients. The mean (standard deviation) half-life of HBsAg in blood was 6.7 (5.5) days, which reflects recent production in the liver and supports strategies aimed at reducing HBsAg production in CHB patients.

Author(s): Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P; Mendler, Michel; Kono, Yuko; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Loomba, Rohit; Familial NAFLD Cirrhosis Research Consortium | Abstract: BackgroundThe risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.MethodsThis is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).ResultsThe prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).ConclusionUsing a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.Trial registrationUcsd irb140084.FundingNational Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Kinder mit gesteigertem Bewegungsdrang landen oft mit „grob- und feinmotorischen Unsicherheiten” auf dem Rezept in der Ergotherapie. Genau wie Otto. Der ist funf Jahre alt, standig in Bewegung und malt nicht gern. Seine Therapeutin vermutete vestibulare Storungen und ging dem Verdacht nach – mit Hangematte & Co. Barbara Andrews ist seit 43 Jahren Ergotherapeutin und war davon 34 Jahre in eigener Praxis tatig. Die Bobath- und SI-Lehrtherapeutin arbeitete mehrere Jahre in Kanada und vier Monate in der Ayres Klinik im kalifornischen Los Angeles. Christiane Kolberg-Neuesus ist seit 25 Jahren Ergotherapeutin. Die Bobath- und SI-Lehrtherapeutin arbeitete im Kinderneurologischen Zentrum in Mainz, in der Praxis von Barbara Andrews und aktuell in einer Praxis bei Koblenz.

Two decades ago, minimally invasive surgery (MIS) was introduced and led to a revolution in modern surgery. Currently MIS procedures are the standard of care for many surgical interventions and patients often seek out surgeons with special training in MIS. Today, natural orifice transluminal endoscopic surgery (NOTES) appears to be on the threshold of another such revolution. We surmise that its advantages are similar to those of other MIS procedures, but there are no associated abdominal wall complications as there are no abdominal incisions. To date, there is no data evaluating women’s perceptions of such a procedure and their willingness to consent to this type of surgical approach. We surveyed 100 women who were given a written description of MIS and NOTES surgery along with a 10-question survey exploring their concerns and opinions regarding transvaginal surgery. The majority of women (68%) indicated that they would want a transvaginal procedure in the future because of decreased risk of hernia and decreased operative pain (90 and 93%, respectively), while only 39% were concerned with the improved cosmesis of NOTES surgery. Of the women polled, nulliparous women and those under age 45 years were significantly more often concerned with how transvaginal surgery may affect healthy sexual life and fertility issues (p

The goal of this full-day workshop is to create a place where people can share experiences, plans, and questions about teaching Participatory Design (PD). We aim to create a context for all of us to talk about how we design and set up courses, what challenges we face and how we solve them. The workshop is for people who are interested in the way people teach as well as in what is taught and what resources are gathered to aid the process. During the workshop, we will explore in an interactive manner how constructivist approaches to teaching can support the teaching and learning of participatory design in academic and non-academic contexts. We will also discuss experiences in using recent material such as the new (2012) PD Handbook. We hope that this dialogue can become a regular part of PDC.

This paper presents a novel solution strategy for the synthesis of multiproduct and multihost protein production processes. There are several possible hosts that may express each of the products, and different downstream processing separation and purification tasks are needed, which in part depend on the host selection. Moreover, alternative unit operations may be available for some of these separation tasks. Finally, these processing units may be arranged in different configurations. A single mixed-integer optimization model represents the different decisions involved in synthesizing a plant for producing multiple proteins. The mathematical model optimizes the profit of the multiproduct plant and allows the decisions to be made simultaneously, namely, the choice of hosts, downstream operations, the configuration and size of units, as well as their scheduling. An example is solved for a plant that must produce four proteins for which there are alternative hosts for their expression (Escherichia coli, Chinese hamster ovary cells, and yeast that, depending on the product, may express it as an extracellular or intracellular protein) that require 15 stages with choices of unit operations as well as in or out of phase operations. Given the very large quantity of novel recombinant proteins for a number of novel therapeutic uses presently being approved or "in the pipeline", multiproduct and multihost recombinant protein production plants have recently been or are being built for the manufacture of these products. The strategy presented in this paper is of crucial value for the optimal utilization of such plants.

There are very few middle level advocates who will dispute the value of an advisory program. It has been purported and supported by research that student achievement rises when students have a more personal, caring relationship with an adult in an intimate group setting while still being part of a larger school community. However, many professionals feel that the implementation of an advisory program is not possible, or certainly not worth the effort, unless the district's commitment is more than

The newly discovered Weddell Fan, Antarctica, covers 0.75 million km2. The adjacent continental shelf is characterized by deep, rugged topography; the inner shelf is covered by a grounded polar ice sheet. The upper fan has numerous deep, V-shaped canyons that intersect a slope-base, leveed fan valley. Piston cores from the valley contain disorganized gravel grading upward into graded gravel and sand. Levee cores contain interbedded hemipelagic sediments and fine-grained turbidites. The lower fan is sand-rich. Sediment supply to the fan apparently occurred before development of glacial shelf topography and during a more temperate glacial setting.

(1944). Posture Wears a Uniform. The Journal of Health and Physical Education: Vol. 15, No. 9, pp. 486-520.