Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly

PURPOSE: Cushing’s disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia. METHODS: Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed. RESULTS: The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3–67.0 %) than in patients with CD treated with pasireotide SC (68.4–73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791–799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875–884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320–326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914–924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues. CONCLUSIONS: Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly. Hyperglycemic effects associated with pasireotide have a predictable pattern, can be managed with antidiabetic agents, and are reversible upon discontinuation

ERTS Applications in earthquake research and mineral exploration in California

Examples that ERTS imagery can be effectively utilized to identify, locate, and map faults which show geomorphic evidence of geologically recent breakage are presented. Several important faults not previously known have been identified. By plotting epicenters of historic earthquakes in parts of California, Sonora, Mexico, Arizona, and Nevada, we found that areas known for historic seismicity are often characterized by abundant evidence of recent fault and crustal movements. There are many examples of seismically quiet areas where outstanding evidence of recent fault movements is observed. One application is clear: ERTS-1 imagery could be effectively utilized to delineate areas susceptible to earthquake recurrence which, on the basis of seismic data alone, may be misleadingly considered safe. ERTS data can also be utilized in planning new sites in the geophysical network of fault movement monitoring and strain and tilt measurements

Matrix Description of Interacting Theories in Six Dimensions

We propose descriptions of interacting (2,0) supersymmetric theories without gravity in six dimensions in the infinite momentum frame. They are based on the large $N$ limit of quantum mechanics or 1+1 dimensional field theories on the moduli space of $N$ instantons in \IR^4.Comment: 10 pages, harvmac bi

Using the West Key Number System as a Data Collection and Coding Device for Empirical Legal Scholarship: Demonstrating the Method Via a Study of Contract Interpretation

Empirical research is an increasingly important type of legal scholarship. Such research generally requires the collection and coding of large quantities of data. These tasks pose critical challenges for legal scholars. Most crucially, they are often resource-intensive. The primary purpose of this article is to explain how researchers can use the West Key Number System to dramatically streamline the process of data collection and coding. The article accomplishes this, in part, through a demonstration: it employs the Key Number System to conduct an empirical study of contract interpretation. Contract interpretation is one of the most significant areas of commercial law. And the subject has received considerable scholarly attention during the last decade. Virtually all academic work in this field is doctrinal or theoretical. But numerous contract interpretation issues cry out for empirical investigation. The secondary purpose of this article is to test one of the central claims in the judicial and academic debate over the optimal method of contract interpretation—the claim that the “contextualist” approach to interpretation results in more litigation over the meaning of contracts than does the “textualist” approach. The results of the study set forth below are inconsistent with that thesis. By thirteen of fourteen measures, there was no statistically significant difference in the amount of interpretation litigation between textualist and contextualist regimes. And for the fourteenth measure, while there was a statistically significant difference, the result was the opposite of that predicted by textualist theory: there was more litigation under textualism

A Case for Grade Inflation in Legal Education

This Article contends that every American law school ought to substantially eliminate C grades by setting its good academic standing grade point average at the B- level. Grading systems that require or encourage law professors to award a significant number of C marks are flawed for two reasons. First, low grades damage students\u27 placement prospects. Employers frequently consider a job candidate\u27s absolute GPA in making hiring decisions. If a school systematically assigns inferior grades, its students are at an unfair disadvantage when competing for employment with students from institutions that award mostly A\u27s and B\u27s. Second, marks in the C range injure students psychologically. Students perceive C\u27s as a sign of failure. Accordingly, when they receive such grades, their stress level is exacerbated in unhealthy ways. This psychological harm is both intrinsically problematic and compromises the educational process. Substantially eliminating C grades will bring about critical improvements in *488 both the fairness of the job market and the mental well-being of our students. These benefits outweigh any problems that might be caused or aggravated by inflated grades. C marks virtually always denote unsatisfactory work in American graduate education. Law schools are the primary exception to this convention. It is time we adopted the practice followed by the rest of the academy

Contract Interpretation Enforcement Costs: An Empirical Study of Textualism Versus Contextualism Conducted Via the West Key Number System

This Article sets forth an empirical study of a central issue in the judicial and academic debate over the optimal method of contract interpretation: Whether “textualism” or “contextualism” best minimizes contract enforcement costs. The study measured enforcement costs in twelve ways. Under each of those measures, there was no statistically significant difference in the level of interpretation litigation between textualist and contextualist regimes. Accordingly, the study finds no support for either the textualist hypothesis that contextualism has higher enforcement costs or the contextualist counter-hypothesis that textualism has higher enforcement costs. The study herein was conducted via the West Key Number System. It is the second study of contract interpretation enforcement costs that I have completed employing that tool. In a prior article, I presented the first study and discussed how to use the Key Number System for empirical research generally. This paper expands on the analysis of the Key Number System from the earlier article. It also addresses how the complexity and confusion in the interpretation caselaw create challenges for empirical work concerning contract interpretation

Using the West Key Number System as a Data Collection and Coding Device for Empirical Legal Scholarship: Demonstrating the Method Via a Study of Contract Interpretation

Empirical research is an increasingly important type of legal scholarship. Such research generally requires the collection and coding of large quantities of data. These tasks pose critical challenges for legal scholars. Most crucially, they are often resource-intensive. The primary purpose of this article is to explain how researchers can use the West Key Number System to dramatically streamline the process of data collection and coding. The article accomplishes this, in part, through a demonstration: it employs the Key Number System to conduct an empirical study of contract interpretation. Contract interpretation is one of the most significant areas of commercial law. And the subject has received considerable scholarly attention during the last decade. Virtually all academic work in this field is doctrinal or theoretical. But numerous contract interpretation issues cry out for empirical investigation. The secondary purpose of this article is to test one of the central claims in the judicial and academic debate over the optimal method of contract interpretation—the claim that the “contextualist” approach to interpretation results in more litigation over the meaning of contracts than does the “textualist” approach. The results of the study set forth below are inconsistent with that thesis. By thirteen of fourteen measures, there was no statistically significant difference in the amount of interpretation litigation between textualist and contextualist regimes. And for the fourteenth measure, while there was a statistically significant difference, the result was the opposite of that predicted by textualist theory: there was more litigation under textualism