An Unbiased Survey for Outflows in the W3 and W5 Star-Formation Regions

During their birth all stars undergo periods of copious mass loss, frequently characterized by the occurrence of bipolar outflows. These outflows are believed to play a fundamental role in the star formation process. However the exact outflow generating method is obscure at present. To elucidate this problem we are investigating whether the flow properties are correlated over the entire protostellar mass spectrum. Progress in this area requires that we assemble a statistically valid sample of high-mass outflow systems. This is necessary since existing catalogues of such objects are heterogeneous and statistically incomplete.Comment: 2 pages, 1 figure, uses newpasp.sty. To appear in "Hot Star Workshop III: The Earliest Phases of Massive Star Birth" (ed. P.A. Crowther

Clearance and Phosphorylation of Alpha-Synuclein Are Inhibited in Methionine Sulfoxide Reductase A Null Yeast Cells

Aggregated α-synuclein and the point mutations Ala30Pro and Ala53Thr of α-synuclein are associated with Parkinson’s disease. The physiological roles of α-synuclein and methionine oxidation of the α-synuclein protein structure and function are not fully understood. Methionine sulfoxide reductase A (MsrA) reduces methionine sulfoxide residues and functions as an antioxidant. To monitor the effect of methionine oxidation to α-synuclein on basic cellular processes, α-synucleins were expressed in msrA null mutant and wild-type yeast cells. Protein degradation was inhibited in the α-synuclein-expressing msrA null mutant cells compared to α-synuclein-expressing wild-type cells. Increased inhibition of degradation and elevated accumulations of fibrillated proteins were observed in SynA30P-expressing msrA null mutant cells. Additionally, methionine oxidation inhibited α-synuclein phosphorylation in yeast cells and in vitro by casein kinase 2. Thus, a compromised MsrA function combined with α-synuclein overexpression may promote processes leading to synucleinopathies

Which is more cost‐effective under the MELD system: primary liver transplantation, or salvage transplantation after hepatic resection or after loco‐regional therapy for hepatocellular carcinoma within Milan criteria?

AbstractObjectiveThe optimal strategy for treating hepatocellular carcinoma (HCC), a disease with increasing incidence, in patients with Child–Pugh class A cirrhosis has long been debated. This study evaluated the cost‐effectiveness of hepatic resection (HR) or locoregional therapy (LRT) followed by salvage orthotopic liver transplantation (SOLT) vs. that of primary orthotopic liver transplantation (POLT) for HCC within the Milan Criteria.MethodsA Markov‐based decision analytic model simulated outcomes, expressed in costs and quality‐adjusted life years (QALYs), for the three treatment strategies. Baseline parameters were determined from a literature review. Sensitivity analyses tested model strength and parameter variability.ResultsBoth HR and LRT followed by SOLT were associated with earlier recurrence, decreased survival, increased costs and decreased quality of life (QoL), whereas POLT resulted in decreased recurrence, increased survival, decreased costs and increased QoL. Specifically, HR/SOLT yielded 3.1QALYs (at US$96000/QALY) and LRT/SOLT yielded 3.9QALYs (at US$74000/QALY), whereas POLT yielded 5.5QALYs (at US$52000/QALY). Sensitivity analyses supported these findings at clinically meaningful probabilities.ConclusionsUnder the Model for End‐stage Liver Disease (MELD) system, in patients with HCC within the Milan Criteria, POLT increases survival and QoL at decreased costs compared with HR or LRT followed by SOLT. Therefore, POLT is the most cost‐effective strategy for the treatment of HCC

Is liver transplantation using organs donated after cardiac death cost‐effective or does it decrease waitlist death by increasing recipient death?

AbstractObjectivesThe aim of this study was to evaluate the cost‐effectiveness in liver transplantation (LT) of utilizing organs donated after cardiac death (DCD) compared with organs donated after brain death (DBD).MethodsA Markov‐based decision analytic model was created to compare two LT waitlist strategies distinguished by organ type: (i) DBD organs only, and (ii) DBD and DCD organs. The model simulated outcomes for patients over 10 years with annual cycles through one of four health states: survival; ischaemic cholangiopathy; retransplantation, and death. Baseline values and ranges were determined from an extensive literature review. Sensitivity analyses tested model strength and parameter variability.ResultsOverall survival is decreased, and biliary complications and retransplantation are increased in recipients of DCD livers. Recipients of DBD livers gained 5.6 quality‐adjusted life years (QALYs) at a cost of US$69 000/QALY, whereas recipients on the DBD + DCD LT waitlist gained 6.0 QALYs at a cost of US$61 000/QALY. The DBD + DCD organ strategy was superior to the DBD organ‐only strategy.conclusionsThe extension of life and quality of life provided by DCD LT to patients on the waiting list who might otherwise not receive a liver transplant makes the continued use of DCD livers cost‐effective

Which is more cost‐effective under the MELD system: primary liver transplantation, or salvage transplantation after hepatic resection or after loco‐regional therapy for hepatocellular carcinoma within Milan criteria?

AbstractObjectiveThe optimal strategy for treating hepatocellular carcinoma (HCC), a disease with increasing incidence, in patients with Child–Pugh class A cirrhosis has long been debated. This study evaluated the cost‐effectiveness of hepatic resection (HR) or locoregional therapy (LRT) followed by salvage orthotopic liver transplantation (SOLT) vs. that of primary orthotopic liver transplantation (POLT) for HCC within the Milan Criteria.MethodsA Markov‐based decision analytic model simulated outcomes, expressed in costs and quality‐adjusted life years (QALYs), for the three treatment strategies. Baseline parameters were determined from a literature review. Sensitivity analyses tested model strength and parameter variability.ResultsBoth HR and LRT followed by SOLT were associated with earlier recurrence, decreased survival, increased costs and decreased quality of life (QoL), whereas POLT resulted in decreased recurrence, increased survival, decreased costs and increased QoL. Specifically, HR/SOLT yielded 3.1QALYs (at US$96000/QALY) and LRT/SOLT yielded 3.9QALYs (at US$74000/QALY), whereas POLT yielded 5.5QALYs (at US$52000/QALY). Sensitivity analyses supported these findings at clinically meaningful probabilities.ConclusionsUnder the Model for End‐stage Liver Disease (MELD) system, in patients with HCC within the Milan Criteria, POLT increases survival and QoL at decreased costs compared with HR or LRT followed by SOLT. Therefore, POLT is the most cost‐effective strategy for the treatment of HCC

History of the Innovation of Damage Control for Management of Trauma Patients: 1902-2016

Objective: To review the history of the innovation of damage control (DC) for management of trauma patients. Background: DC is an important development in trauma care that provides a valuable case study in surgical innovation. Methods: We searched bibliographic databases (1950-2015), conference abstracts (2009-2013), Web sites, textbooks, and bibliographies for articles relating to trauma DC. The innovation of DC was then classified according to the Innovation, Development, Exploration, Assessment, and Long-term study model of surgical innovation. Results: The innovation\u27\u27 of DC originated from the use of therapeutic liver packing, a practice that had previously been abandoned after World War II because of adverse events. It then developed\u27\u27 into abbreviated laparotomy using rapid conservative operative techniques.\u27\u27 Subsequent exploration\u27\u27 resulted in the application of DC to increasingly complex abdominal injuries and thoracic, peripheral vascular, and orthopedic injuries. Increasing use of DC laparotomy was followed by growing reports of postinjury abdominal compartment syndrome and prophylactic use of the open abdomen to prevent intra-abdominal hypertension after DC laparotomy. By the year 2000, DC surgery had been widely adopted and was recommended for use in surgical journals, textbooks, and teaching courses ( assessment\u27\u27 stage of innovation). Long-term study\u27\u27 of DC is raising questions about whether the procedure should be used more selectively in the context of improving resuscitation practices. Conclusions: The history of the innovation of DC illustrates how a previously abandoned surgical technique was adapted and readopted in response to an increased understanding of trauma patient physiology and changing injury patterns and trauma resuscitation practices

The Multiscale Backbone of the Human Phenotype Network Based on Biological Pathways

Background: Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes. Results: The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. We extract the multi-scale information backbone of the PHPN based on the local densities of the network and discarding weak connection. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present examples of expected clinical connections identified by PHPN as proof of principle. Conclusions: We unveil a previously uncharacterized connection between phenotype modules and discuss potential mechanistic connections that are obvious only in retrospect. The PHPN shows tremendous potential to become a useful tool both in the unveiling of the diseases’ common biology, and in the elaboration of diagnosis and treatments

Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence Following Transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146434/1/lt25194.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146434/2/lt25194_am.pd

Biomarkers for ragwort poisoning in horses: identification of protein targets

BACKGROUND: Ingestion of the poisonous weed ragwort (Senecio jacobea) by horses leads to irreversible liver damage. The principal toxins of ragwort are the pyrrolizidine alkaloids that are rapidly metabolised to highly reactive and cytotoxic pyrroles, which can escape into the circulation and bind to proteins. In this study a non-invasive in vitro model system has been developed to investigate whether pyrrole toxins induce specific modifications of equine blood proteins that are detectable by proteomic methods. RESULTS: One dimensional gel electrophoresis revealed a significant alteration in the equine plasma protein profile following pyrrole exposure and the formation of a high molecular weight protein aggregate. Using mass spectrometry and confirmation by western blotting the major components of this aggregate were identified as fibrinogen, serum albumin and transferrin. CONCLUSION: These findings demonstrate that pyrrolic metabolites can modify equine plasma proteins. The high molecular weight aggregate may result from extensive inter- and intra-molecular cross-linking of fibrinogen with the pyrrole. This model has the potential to form the basis of a novel proteomic strategy aimed at identifying surrogate protein biomarkers of ragwort exposure in horses and other livestock

Identification of a Likely Radio Counterpart of the Rapid Burster

We have identified a likely radio counterpart to the low-mass X-ray binary MXB 1730-335 (the Rapid Burster). The counterpart has shown 8.4 GHz radio on/off behavior correlated with the X-ray on/off behavior as observed by the RXTE/ASM during six VLA observations. The probability of an unrelated, randomly varying background source duplicating this behavior is 1-3% depending on the correlation time scale. The location of the radio source is RA 17h 33m 24.61s; Dec -33d 23' 19.8" (J2000), +/- 0.1". We do not detect 8.4 GHz radio emission coincident with type II (accretion-driven) X-ray bursts. The ratio of radio to X-ray emission during such bursts is constrained to be below the ratio observed during X-ray persistent emission at the 2.9-sigma level. Synchrotron bubble models of the radio emission can provide a reasonable fit to the full data set, collected over several outbursts, assuming that the radio evolution is the same from outburst to outburst, but given the physical constraints the emission is more likely to be due to ~hour-long radio flares such as have been observed from the X-ray binary GRS 1915+105.Comment: 28 pages, 4 figures; accepted for publication in ApJ (no changes