Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier function in schizophrenia pathogenesis. However, direct evidence demonstrating an impaired BBB function is missing. In this preliminary study, we used immunohistochemistry and serum immunoglobulin G antibodies to investigate the state of BBB function in formalin-fixed postmortem samples from the hippocampus and surrounding temporal cortex of patients with schizophrenia and controls without (...) schizophrenia matched for age, sex, and race. Since a functional BBB prevents the extravasation of IgGs, detection of IgGs in the parenchyma is used as direct evidence of BBB breakdown. We also developed a semi-quantitative approach to quantify the extent of IgG leak and therein BBB breach. Analysis of our immunohistochemistry data demonstrated a significantly higher incidence of IgG leak in patients with schizophrenia compared to controls. Further, BBB permeability was significantly higher in advanced-age patients with schizophrenia than both advanced-age controls and middle-aged patients with schizophrenia. Male patients with schizophrenia also demonstrated a significant increase in IgG permeability compared to control males. Interestingly, the extravasated IgGs also demonstrated selective immunoreactivity for neurons. Based on these observations, we suggest that BBB dysfunction and IgG autoantibodies could be two key missing pathoetiological links underwriting schizophrenia hippocampal damage. (shrink)

One dark and rainy night, Yuso sexually assaults and tortures Zelan. In escaping from the scene of his crime, he falls heavily and becomes an impotent paraplegic. Instead of treating his fate as divine retribution for his wicked acts, Yuso sees it as sheer bad luck. He shows no remorse for what he has done, and vainly hopes that he will recover his powers, which he now treats as involuntarily hoarded resources to be used on less rainy days. In the (...) presence of others, he pretends that he has turned over a new leaf. He asks for religious and educational books, hoping to make up for his poor education and deprived social background. But he immediately discards them when he is alone in favor of the pornographic magazines which he has bribed a nurse to smuggle in for him. His deception and various obscene acts committed in the hospital are exposed; by the time he comes up for trial, everyone knows that he is still a lustful, sadistic, and unrepentant man. Most retributivists have a sufficient justification for punishing Yuso independently of the social consequences of his punishment. Two features of the case might cause some difficulties. First, Yuso has already experienced considerable suffering and deprivation both before and after his crime, and retributivists might disagree about the relevance of the suffering to his punishment. Secondly, Yuso is unrepentant, and it is unlikely that punishment will change him. This might, as we shall see, create a problem for those who think that the justifying aim of punishment is the moral reform of the offender. (shrink)

This paper discusses the nature of liberty from the point of view of value. Liberty is the highest value for liberals. The root of this liberal view is their particular conception of self. Rawls says 'the self is prior to the ends which are affirmed by it.' This is also the Kantian view of the self: the self is prior to its socially given roles and relationships. Therefore, no end is exempt from possible revision by the self. There is nothing (...) wrong with this basic idea. In fact, all theories agree on free choice of life plan or self-determination. But they disagree about what package of rights and resources best enables people to pursue their own conceptions of the good. However, the liberal view of liberty is based on a metaphysically reasoned idealism. This results in a conception of liberty that is absolute, supreme, and has infinite value compared with other things. Communitarians have several arguments against the liberal view. I consider the following two points to be of utmost import: The liberal view of the self is empty; The liberal view ignores our embeddedness in communal practices. My reasoning is not exactly that of the communitarians. I view 'emptiness' as freedom associated with the substance of an action, which has a value that does not lie in itself. (shrink)

The purpose of this essay is to study the problem of inherent obscurity of the criterion for maximal utility in utilitarianism. For the sake of convenience of analysis, situations of moral actions are classified into four categories. It is shown that morality is flexible, especially in the positive sense, in that a virtuous action can be taken in various ways and/or to various degrees. For some situations it is inherently unclear what the moral requirement is, and whether it is a (...) maximum or a minimum. It is concluded that the schism of the principle of utility between the principle of the good and the principle of the right seems to be inevitable, and the interpretation of the ultimate criterion for maximal utility should be relaxed or interpreted separately and differently according to the situation of action. (shrink)

Adaptive management is commonly identified as a way to address situations where ecological and social uncertainty exists. Two discourses are common: a focus on experimentation, and a focus on collaboration. The roles of experimental and collaborative adaptive management in contemporary practice are reviewed to identify tools for bridging the discourses. Examples include broadening the scope of contributions during the buy-in and goal-setting stages, using conceptual models and decision support tools to include stakeholders in model development, experimentation using indicators of concern (...) to stakeholders, an experimental focus that reflects the level of statistical confidence required by management, and the engagement of stakeholders in data interpretation so that those affected by management outcomes can learn and adapt accordingly. In this context, a framework of questions that managers can use to reflect on both ecological and social uncertainties as they relate to individual management contexts is proposed. (shrink)