21 research outputs found
Research Protocol
This protocol was developed in accordance with the Joanna Briggs Institute (JBI) Reviewers' Manual 2015 - Methodology for JBI Scoping Reviews. This protocol outlines the predefined methodology to be implemented during this research
Tragedies [electronic resource] /
Seneca (c. 4-65 CE) authored verse tragedies that strongly influenced Shakespeare and other Renaissance dramatists. Plots are based on myth, in keeping with classical tradition, but themes reflect imperial Roman politics. Powerful rhetoric conveys intensity and the perspective is much bleaker than in Seneca's prose writings.Includes index.v. I. Hercules. Trojan women. Phoenician women. Medea. Phaedra -- v. II. Oedipus. Agamemnon. Thyestes. Hercules on Oeta. Octavia.Seneca (c. 4-65 CE) authored verse tragedies that strongly influenced Shakespeare and other Renaissance dramatists. Plots are based on myth, in keeping with classical tradition, but themes reflect imperial Roman politics. Powerful rhetoric conveys intensity and the perspective is much bleaker than in Seneca's prose writings.Mode of access: World Wide Web.Description based on print version record
Performance of preclinical models in predicting drugâinduced liver injury in humans: a systematic review
Drugâinduced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidenceâbased methods to investigate the role of preclinical studies in predicting human DILI using two antiâdiabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazoneâ and rosiglitazoneârelated DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidenceâbased methodologies and performed according to preâregistered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in âlowâ or âvery lowâ certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more offâtarget effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liverârelated adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazoneâs potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugsâ offâtarget activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions
Seneca and Epicurus: the Allure of the Other
The philosophical role of Seneca's relationship to Epicuru