The US is more likely to impose sanctions on countries that have poor allies.

For decades, the US has used sanctions against countries and regimes where they seek to encourage change. But what determines whether or not the US imposes sanctions in the first place? In new research that examines more than 50 years of sanctions, Timothy M. Peterson finds that sanctions are more likely to be imposed against countries with poor allies that will not be able to step in with economic assistance. As the target country’s allies become wealthier, it is less likely that sanctions will be put in place

International trade : costs, coercion, and conflict

Title from PDF of title page (University of Missouri--Columbia, viewed on March 7, 2011).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Dissertation advisor: Dr. A. Cooper Drury.Vita.Ph. D. University of Missouri--Columbia 2010.There is a large literature examining the relationship between trade and international politics. However, the majority of extant studies examine the extent of trade interaction, despite acknowledging the potential for states to rely on trade to differing degrees. In this dissertation, I devise measures of potential trade gains and potential trade losses, using these measures to address three important research questions in the study of international relations. First, I look at the relationship between exit costs and conflict, arguing that asymmetry in exit costs is associated with a higher likelihood of militarized conflict. Second, I examine the connection between exit costs and sanction threats, finding that vulnerable states are more likely to be targeted with sanction threats but are not likely to give in to these threats. Finally, I look at the connection between potential trade gains and protectionism, arguing that inelastic demand is associated with lower tariffs for democracies, but higher tariffs for autocracies. This study demonstrates that there is considerable room for further exploration into the connection between trade potential and international outcomes.Includes bibliographical reference

Predicting Emergency Department Volume Using Forecasting Methods to Create a “Surge Response” for Noncrisis Events

Objectives:  This study investigated whether emergency department (ED) variables could be used in mathematical models to predict a future surge in ED volume based on recent levels of use of physician capacity. The models may be used to guide decisions related to on‐call staffing in non–crisis‐related surges of patient volume. Methods:  A retrospective analysis was conducted using information spanning July 2009 through June 2010 from a large urban teaching hospital with a Level I trauma center. A comparison of significance was used to assess the impact of multiple patient‐specific variables on the state of the ED. Physician capacity was modeled based on historical physician treatment capacity and productivity. Binary logistic regression analysis was used to determine the probability that the available physician capacity would be sufficient to treat all patients forecasted to arrive in the next time period. The prediction horizons used were 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 12 hours. Five consecutive months of patient data from July 2010 through November 2010, similar to the data used to generate the models, was used to validate the models. Positive predictive values, Type I and Type II errors, and real‐time accuracy in predicting noncrisis surge events were used to evaluate the forecast accuracy of the models. Results:  The ratio of new patients requiring treatment over total physician capacity (termed the care utilization ratio [CUR]) was deemed a robust predictor of the state of the ED (with a CUR greater than 1 indicating that the physician capacity would not be sufficient to treat all patients forecasted to arrive). Prediction intervals of 30 minutes, 8 hours, and 12 hours performed best of all models analyzed, with deviances of 1.000, 0.951, and 0.864, respectively. A 95% significance was used to validate the models against the July 2010 through November 2010 data set. Positive predictive values ranged from 0.738 to 0.872, true positives ranged from 74% to 94%, and true negatives ranged from 70% to 90% depending on the threshold used to determine the state of the ED with the 30‐minute prediction model. Conclusions:  The CUR is a new and robust indicator of an ED system’s performance. The study was able to model the tradeoff of longer time to response versus shorter but more accurate predictions, by investigating different prediction intervals. Current practice would have been improved by using the proposed models and would have identified the surge in patient volume earlier on noncrisis days.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92015/1/j.1553-2712.2012.01359.x.pd

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents

peer-reviewedThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction

Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates

Nitrogen-containing-bisphosphonates (N-BPs) are widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice.

In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop

Myonuclear Transcription is Responsive to Mechanical Load and DNA Content but Uncoupled from Cell Size During Hypertrophy

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (\u3c 1000 μm2) demonstrated the highest transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy

The Black Hole Mass of NGC 4151: Comparison of Reverberation Mapping and Stellar Dynamical Measurements

We present a stellar dynamical estimate of the black hole (BH) mass in the Seyfert 1 galaxy, NGC 4151. We analyze ground-based spectroscopy as well as imaging data from the ground and space, and we construct 3-integral axisymmetric models in order to constrain the BH mass and mass-to-light ratio. The dynamical models depend on the assumed inclination of the kinematic symmetry axis of the stellar bulge. In the case where the bulge is assumed to be viewed edge-on, the kinematical data give only an upper limit to the mass of the BH of ~4e7 M_sun (1 sigma). If the bulge kinematic axis is assumed to have the same inclination as the symmetry axis of the large-scale galaxy disk (i.e., 23 degrees relative to the line of sight), a best-fit dynamical mass between 4-5e7 M_sun is obtained. However, because of the poor quality of the fit when the bulge is assumed to be inclined (as determined by the noisiness of the chi^2 surface and its minimum value), and because we lack spectroscopic data that clearly resolves the BH sphere of influence, we consider our measurements to be tentative estimates of the dynamical BH mass. With this preliminary result, NGC 4151 is now among the small sample of galaxies in which the BH mass has been constrained from two independent techniques, and the mass values we find for both bulge inclinations are in reasonable agreement with the recent estimate from reverberation mapping (4.57[+0.57/-0.47]e7 M_sun) published by Bentz et al.Comment: 20 pages, including 11 low-res figures. Accepted for publication in ApJ. High resolution version available upon reques