Sexual well-being and diurnal cortisol after prostate cancer treatment.

Sexual dysfunction and psychological distress are common after prostate cancer. Research has not examined the role of neuroendocrine markers of stress (e.g. cortisol). This study examines whether sexual functioning or sexual bother is associated with diurnal cortisol. Men treated for prostate cancer completed the University of California-Los Angeles Prostate Cancer Index and provided saliva samples four times daily for cortisol assessment. Higher sexual bother, but not sexual functioning, was associated with steeper cortisol slope. Better sexual functioning, and not sexual bother, was significantly associated with the cortisol awakening response. Assessment of stress and stress-reducing interventions might be warranted in sexual rehabilitation after prostate cancer

ECONOMIC AND ENVIRONMENTAL EVALUATION OF DAIRY MANURE UTILIZATION FOR YEAR ROUND CROP PRODUCTION

The production of excess on-farm manure is placing continuous pressures on dairy producers to meet or exceed standards for environmental regulations while maintaining profitability and competitiveness. Evaluation of the effects of recycling nutrients on the profitability of the whole farm enterprise is important for a dairy operation. The objective of this study was to develop a linear programming model that evaluates the economic performance of a dairy operation considering production and environmental constraints. The main goal was to maximize profits from the dairy enterprise considering milk production, manure production, crop production while maintaining a balance of nutrients in the system. Results from simulation analyses showed greater effects on total farm profits at the more restrictive P-based than N-based manure application rates.Environmental Economics and Policy,

Territorial Integrity Treaties, Uti Possidetis, and Armed Conflict over Territory

Paper presented at the 2006 Shambaugh Conference Building Synergies: Institutions and Cooperation in World Politics, University of Iowa, 13 October 2006. Earlier versions of this paper were presented at the 37th Annual Meeting of the Peace Science Society (International), Ann Arbor, November 2003, and the 45th Annual Meeting of the International Studies Association, Montreal, March 2004. The authors wish to thank Ashley Leeds, Bumba Mukherjee, Chris Reenock, and Jeff Staton for their valuable comments and suggestions, while taking full blame for all errors and interpretations herein. Abstract A recent article suggests that a norm of territorial integrity spread rapidly across the globe during the twentieth century. While the successful acquisition of territory by force has become much less frequent, though, there have been numerous attempts to acquire territory by force during this time, and there appear to be several different types of obligations in territorial integrity treaties. Drawing from the content of treaties with territorial integrity provisions, we reconceptualize the norm to distinguish between treaties guaranteeing territorial integrity in a general sense and those that only proscribe the acquisition of territory by force, and we examine an important precursor in the nineteenth-century Latin American norm of uti possidetis juris. We find that both norms seem to have been associated with generally increased low-level conflict over territory but (at least for general territorial integrity obligations and for the Latin American states that developed uti possidetis) less of the more intense forms of conflict

Measuring Health Care Costs of Individuals with Employer-Sponsored Health Insurance in the U.S.: A Comparison of Survey and Claims Data

As the core nationally representative health expenditure survey in the United States, the Medical Expenditure Panel Survey (MEPS) is increasingly being used by statistical agencies to track expenditures by disease. However, while MEPS provides a wealth of data, its small sample size precludes examination of spending on all but the most prevalent health conditions. To overcome this issue, statistical agencies have turned to other public data sources, such as Medicare and Medicaid claims data, when available. No comparable publicly available data exist for those with employer-sponsored insurance. While large proprietary claims databases may be an option, the relative accuracy of their spending estimates is not known. This study compared MEPS and MarketScan estimates of annual per person health care spending on individuals with employer-sponsored insurance coverage. Both total spending and the distribution of annual per person spending differed across the two data sources, with MEPS estimates 10 percent lower on average than estimates from MarketScan. These differences appeared to be a function of both underrepresentation of high expenditure cases and underestimation across the remaining distribution of spending.

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

Lipid analogues as potential drugs for the regulation of mitochondrial cell death

The mitochondrion plays an important role in the production of energy as ATP, the regulation of cell viability and apoptosis, and the biosynthesis of major structural and regulatory molecules, such as lipids. During ATP production, reactive oxygen species are generated that alter the intracellular redox state and activate apoptosis. Mitochondrial dysfunction is a well-recognized component of the pathogenesis of diseases such as cancer. Understanding mitochondrial function, and how this is dysregulated in disease, offers the opportunity for the development of drug molecules to specifically target such defects. Altered energy metabolism in cancer, in which ATP production occurs largely by glycolysis, rather than by oxidative phosphorylation, is attributable in part to the up-regulation of cell survival signalling cascades. These pathways also regulate the balance between pro- and anti-apoptotic factors that may determine the rate of cell death and proliferation. A number of anti-cancer drugs have been developed that target these factors and one of the most promising groups of agents in this regard are the lipid-based molecules that act directly or indirectly at the mitochondrion. These molecules have emerged in part from an understanding of the mitochondrial actions of naturally occurring fatty acids. Some of these agents have already entered clinical trials because they specifically target known mitochondrial defects in the cancer cell.Support of research in the authors' laboratory by the Australian National Health and Medical Research Council is gratefully acknowledged

A Helium-Surface Interaction Potential of Bi2_2Te3_3(111) from Ultrahigh-Resolution Spin-Echo Measurements

We have determined an atom-surface interaction potential for the He$-$Bi$_2$Te$_3$(111) system by analysing ultrahigh resolution measurements of selective adsorption resonances. The experimental measurements were obtained using $^3$He spin-echo spectrometry. Following an initial free-particle model analysis, we use elastic close-coupling calculations to obtain a three-dimensional potential. The three-dimensional potential is then further refined based on the experimental data set, giving rise to an optimised potential which fully reproduces the experimental data. Based on this analysis, the He$-$Bi$_2$Te$_3$(111) interaction potential can be described by a corrugated Morse potential with a well depth $D=(6.22\pm0.05)~\mathrm{meV}$, a stiffness $\kappa =(0.92\pm0.01)~\mathrm{\AA}^{-1}$ and a surface electronic corrugation of $(9.6\pm0.2)$% of the lattice constant. The improved uncertainties of the atom-surface interaction potential should also enable the use in inelastic close-coupled calculations in order to eventually study the temperature dependence and the line width of selective adsorption resonances