Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.

Common law and civil law as pro-market adaptations

We argue that in the development of the Western legal system, cognitive departures are themain determinant of the optimal degree of judicial rule-making. Judicial discretion, seen here as the main distinguishing feature between both legal systems, is introduced in civil law jurisdictions to protect, rather than to limit, freedom of contract against potential judicial backlash. Such protection was unnecessary in common law countries, where free-market relations enjoyed safer judicial ground mainly due to their relatively gradual evolution, their reliance on practitioners as judges, and the earlier development of institutional checks and balances that supported private property rights. In our framework, differences in costs and benefits associated with self-interest and lack of information require a cognitive failure to be active.

Towards equivalent health care of prisoners: European soft law and public health policy in Geneva.

Prisoners have a right to health care and to be protected against inhumane and degrading treatment. Health care personnel and public policy makers play a central role in the protection of these rights and in the pursuit of public health goals. This article examines the legal framework for prison medicine in the canton of Geneva, Switzerland and provides examples of this framework that has shaped prisoners' medical care, including preventive measures. Geneva constitutes an intriguing example of how the Council of Europe standards concerning prison medicine have acquired a legal role in a Swiss canton. Learning how these factors have influenced implementation of prison medicine standards in Geneva may be helpful to public health managers elsewhere and encourage the use of similar strategies.

Corporate criminal law and organization incentives: A managerial perspective

Corporate criminal liability puts a serious challenge to the economictheory of enforcement. Are corporate crimes different from other crimes?Are these crimes best deterred by punishing individuals, punishing corporations, or both? What is optimal structure of sanctions? Shouldcorporate liability be criminal or civil? This paper has two majorcontributions to the literature. First, it provides a common analyticalframework to most results presented and largely discussed in the field.In second place, by making use of the framework, we provide new insightsinto how corporations should be punished for the offenses committed bytheir employees.

Water planning law and government.

Water planning efforts typically identify problems and needs. But simply calling attention to issues is usually not enough to spur action; the end result of many well-intentioned planning efforts is a report that ends up gathering dust on a shelf. Vague recommendations like “Water conservation measures should be implemented” usually accomplish little by themselves as they don’t assign responsibility to anyone. Success is more likely when an implementation strategy — who can and should do what — is developed as part of the planning process. The more detailed and specific the implementation strategy, the greater the chance that something will actually be done. The question then becomes who has the legal authority or responsibility to do what? Are new laws and programs needed or can existing ones be used to implement the recommendations? ... This document is divided into four main parts. The first, “Carrots and Sticks” looks at two basic approaches — regulatory and non-regulatory — that can be, and are, used to carry out water policy. Both have advantages and disadvantages that need to be considered. The second, “The powers of federal, state and local governments…,” looks at the constitutional powers the federal government and state and local governments have to carry out water policy. An initial look at the U. S. Constitution might suggest the federal government’s regulatory authority over water is limited but, in fact, its powers are very substantial. States have considerable authority to do a number of things but have to be mindful of any federal efforts that might conflict with those state efforts. And local governments can only do those things the state constitution or state legislature says they can do and must conform to any requirements or limitations on those powers that are contained in the enabling acts. Parts three and four examine in more detail the main programs and agencies at the federal level as well as Iowa’s state and local levels and the roles they play in national and state water policy.

Floods of June 17, 1990 and July 9, 1993, Along Squaw Creek and the South Skunk River in Ames, Iowa, and Vicinity, HR-140, 1996

Water-surface-elevation profiles and peak discharges for the floods of June 17, 1990, and July 9, 1993, along Squaw Creek and the South Skunk River, in Ames, Iowa, are presented in this report. The maximum flood-peak discharge of 24,300 cubic feet per second for the streamflow-gaging station on Squaw Creek at Ames, Iowa (station number 05470500) occurred on July 9, 1993. This discharge was 80 percent larger than the 100-year recurrence-interval discharge and exceeded the previous record flood-peak discharge of June 17, 1990, by 94 percent. The July 9, 1993, flood-peak discharge of 26,500 cubic feet per second on the South Skunk River below Squaw Creek (station number 05471000) was also a peak of record, exceeding the previous record flood-peak discharge of June 27,1975, by 80 percent, and the 100-year recurrence-interval discharge by 60 percent. A flood history describes rainfall conditions for floods that occurred during 1990 and 1993.

The ambiguous disruption of gender-role expectations in the law and the lady name

The main purpose of this research project is to analyse the major female figures in Wilkie Collins' work of fiction The Law and the Lady, in relation to the times in which the novel was produced and the situation of women in the Victorian era. After taking into account the major events of the life of the author, as well as the sociohistorical conditions of the Victorian period, I try to reach conclusions about whether the author challenges gender-role expectations, presenting the readers with a new form of femininity, of if, on the contrary, he preserves and maintains a conservative, traditional perspective of femininity and female conventions proper to the established parameters of the times in which he lived. Keywords:

Water Planning Law and Government, November 2008

Water planning efforts typically identify problems and needs. But simply calling attention to issues is usually not enough to spur action; the end result of many well-intentioned planning efforts is a report that ends up gathering dust on a shelf. Vague recommendations like “Water conservation measures should be implemented” usually accomplish little by themselves as they don’t assign responsibility to anyone. Success is more likely when an implementation strategy — who can and should do what — is developed as part of the planning process. The more detailed and specific the implementation strategy, the greater the chance that something will actually be done.

Internet, Law and Politics. A decade of transformations.

Proceedings of Internet, Law and Politics. A decade of transformations.

Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment

The dose makes the poison, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to"diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to 'oncobiguanides' with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides