Stabilization of troponin I for applications in clinical chemistry and forensic medicine. Cardiac troponin I: A time of death marker

Cardiac troponin I (cTnI) is one of the most useful serum marker test for the determination of myocardial infarction (MI). The first commercial assay of cTnI was released for medical use in the United States and Europe in 1995. It is useful in determining if the source of chest pains, whose etiology may be unknown, is cardiac related. Cardiac TnI is released into the bloodstream following myocardial necrosis (cardiac cell death) as a result of an infarct (heart attack). In this research project the utility of cardiac troponin I as a potential marker for the determination of time of death is investigated. The approach of this research is not to investigate cTnI degradation in serum/plasma, but to investigate the proteolytic breakdown of this protein in heart tissue postmortem. If our hypothesis is correct, cTnI might show a distinctive temporal degradation profile after death. This temporal profile may have potential as a time of death marker in forensic medicine. The field of time of death markers has lagged behind the great advances in technology since the late 1850's. Today medical examiners are using rudimentary time of death markers that offer limited reliability in the medico-legal arena. Cardiac TnI must be stabilized in order to avoid further degradation by proteases in the extraction process. Chemically derivatized magnetic microparticles were covalently linked to anti-cTnI monoclonal antibodies. A charge capture approach was also used to eliminate the antibody from the magnetic microparticles given the negative charge on the microparticles. The magnetic microparticles were used to extract cTnI from heart tissue homogenate for further bio-analysis. Cardiac TnI was eluted from the beads with a buffer and analyzed. This technique exploits banding pattern on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by a western blot transfer to polyvinylidene fluoride (PVDF) paper for probing with anti-cTnI monoclonal antibodies. Bovine hearts were used as a model to establish the relationship of time of death and concentration/band-pattern given its homology to human cardiac TnI. The final concept feasibility was tested with human heart samples from cadavers with known time of death. ^

Examining moderators of the hindsight bias in the context of civil legal decision -making: Counterfactuals, causal proximity, and self -referencing

The current research sought to clarify the diverging relationships between counterfactual thinking and hindsight bias observed in the literature thus far. In a non-legal context, Roese and Olson (1996) found a positive relationship between counterfactuals and hindsight bias, such that counterfactual mutations that undid the outcome also increased participants’ ratings of the outcome’s a priori likelihood. Further, they determined that this relationship is mediated by causal attributions about the counterfactually mutated antecedent event. Conversely, in the context of a civil lawsuit, Robbennolt and Sobus (1997) found that the relationship between counterfactual thinking and hindsight bias is negative. The current research sought to resolve the conflicting findings in the literature within a legal context. ^ In Experiment One, the manipulation of the normality of the defendant’s target behavior, designed to manipulate participants’ counterfactual thoughts about said behavior, did moderate the hindsight effect of outcome knowledge on mock jurors’ judgments of the foreseeability of that outcome as well as their negligence verdicts. Although I predicted that counterfactual thinking would increase, or exacerbate, the hindsight bias, as found by Roese and Olson (1996), my results provided some support for Robbenolt and Sobus’s (1997) finding that counterfactual thinking decreases the hindsight bias. Behavior normality did not moderate the hindsight effect of outcome knowledge in Experiment Two, nor did causal proximity in Experiment Three. ^ Additionally, my hypothesis that self-referencing may be an effective hindsight debiasing technique received little support across the three experiments. Although both the self-referencing instructions and self-report measure consistently decreased mock jurors’ likelihood of finding the defendant negligent, and self-referencing instructions decreased their foreseeability ratings in studies two and three, the self-referencing manipulation did not interact with outcome knowledge to moderate a hindsight bias effect on either foreseeability or negligence judgments. The consistent pattern of results across the three experiments, however, suggests that self-referencing may be an effective technique in reducing the likelihood of negligence verdicts.^

Examining Moderators of the Hindsight Bias in the Context of Civil Legal Decision-Making: Counterfactuals, Causal Proximity, and Self-Referencing

The current research sought to clarify the diverging relationships between counterfactual thinking and hindsight bias observed in the literature thus far. In a non-legal context, Roese and Olson (1996) found a positive relationship between counterfactuals and hindsight bias, such that counterfactual mutations that undid the outcome also increased participants’ ratings of the outcome’s a priori likelihood. Further, they determined that this relationship is mediated by causal attributions about the counterfactually mutated antecedent event. Conversely, in the context of a civil lawsuit, Robbennolt and Sobus (1997) found that the relationship between counterfactual thinking and hindsight bias is negative. The current research sought to resolve the conflicting findings in the literature within a legal context. In Experiment One, the manipulation of the normality of the defendant’s target behavior, designed to manipulate participants’ counterfactual thoughts about said behavior, did moderate the hindsight effect of outcome knowledge on mock jurors’ judgments of the foreseeability of that outcome as well as their negligence verdicts. Although I predicted that counterfactual thinking would increase, or exacerbate, the hindsight bias, as found by Roese and Olson (1996), my results provided some support for Robbenolt and Sobus’s (1997) finding that counterfactual thinking decreases the hindsight bias. Behavior normality did not moderate the hindsight effect of outcome knowledge in Experiment Two, nor did causal proximity in Experiment Three. Additionally, my hypothesis that self-referencing may be an effective hindsight debiasing technique received little support across the three experiments. Although both the self-referencing instructions and self-report measure consistently decreased mock jurors’ likelihood of finding the defendant negligent, and self-referencing instructions decreased their foreseeability ratings in studies two and three, the self-referencing manipulation did not interact with outcome knowledge to moderate a hindsight bias effect on either foreseeability or negligence judgments. The consistent pattern of results across the three experiments, however, suggests that self-referencing may be an effective technique in reducing the likelihood of negligence verdicts.