Evaluation of drug toxicity in clinical trials

An increasing number of drugs removed from the market because of unacceptable toxicity raises concerns regarding preapproval testing of drug safety. In the present paper it is postulated that the non-inferiority type of trial should be abandoned in favor of the superiority trial with active controls and less stringent (p<0.1, both for efficacy and toxicity) statistics. This approach will increase sensitivity of detection of drug-induced adverse effects at the expense of increasing false positive results regarding the difference in efficacy between the tested and reference drug. Such a move will increase the protection of future patients. In addition, the proposed design is far more acceptable from the clinical (e.g. no need to specify the statistically expected “unimportant” number of deaths) and ethical points of view, as well as being favored by the strong incentive of involved parties. In the second part of this paper arguments are presented in favor of the hypothesis that placebo (still used in some superiority trials) does not induce adverse effects. The assertion that placebo may induce adverse effects is probably biased by the nature of the clinical experiment. Such a conclusion is supported by studies indicating that placebo-induced adverse effects are disease — and treatment — specific. The modification of clinical trials according to the proposed changes may increase the trials’ sensitivity at detecting adverse effects of drugs. A lecture on the subject of this paper was presented at the 6th International Bioethics Conference on the subject of ‘The Responsible Conduct of Basic and Clinical Research’, held in Warsaw, Poland, 3–4 June 2005.     

The Pentus Theorem for Lambek Calculus with Simple Nonlogical Axioms

The Lambek calculus introduced in Lambek [6] is a strengthening of the type reduction calculus of Ajdukiewicz [1]. We study Associative Lambek Calculus L in Gentzen style axiomatization enriched with a finite set Γ of nonlogical axioms, denoted by L(Γ).It is known that finite axiomatic extensions of Associative Lambek Calculus generate all recursively enumerable languages (see Buszkowski [2]). Then we confine nonlogical axioms to sequents of the form p → q, where p and q are atomic types. For calculus L(Γ) we prove interpolation lemma (modifying the Roorda proof for L [10]) and the binary reduction lemma (using the Pentus method [9] with modification from [3]). In consequence we obtain the weak equivalence of the Context-Free Grammars and grammars based on L(Γ).     

Enhanced involvement of brain vasopressin V1 receptors in cardiovascular responses to stress in rats with myocardial infarction

Stress is one of the factors provoking cardiovascular complications. The purpose of the study was to explore the role of vasopressin (VP) in central control of arterial blood pressure and heart rate under resting conditions and during stimulation by an alarming stress (air jet stress) in myocardial infarct-induced cardiac failure. Six groups of male Sprague Dawley (SD) rats were subjected either to sham surgery (sham rats) or to ligation of a left coronary artery (infarcted rats). After 5 weeks both infarcted and sham rats were subjected either to intracerebroventricular infusion of artificial cerebrospinal fluid (aCSF) (sham aCSF and infarcted aCSF), [Arg8]-VP (sham VP and infarcted VP) or VP V1a receptor antagonist (d(CH2)5[Tyr(Me)2Ala-]VP, sham V1ANT and infarcted V1ANT). Air jet stress elicited significantly greater increases in mean arterial blood pressure (MABP) and heart rate in the infarcted aCSF than in the sham aCSF rats. Intracerebroventricular infusion of V1ANT significantly reduced resting MABP and MABP and heart rate increases in response to stress in the infarcted but not in the sham rats. Intracerebroventricular infusion of VP elicited a significant increase in resting MABP in the infarcted VP but not in the sham VP rats. The results provide evidence for enhanced engagement of the brain V1 VP receptors in regulation of resting MABP and in generation of exaggerated cardiovascular responses to air jet stress during the post-infarct state.     

Number of Extensions of Non-Fregean Logics

We show that there are continuum many different extensions of SCI (the basic theory of non-Fregean propositional logic) that lie below WF (the Fregean extension) and are closed under substitution. Moreover, continuum many of them are independent from WB (the Boolean extension), continuum many lie above WB and are independent from WH (the Boolean extension with only two values for the equality relation), and only countably many lie between WH and WF.     

Age equivalence in switch costs for prosaccade and antisaccade tasks

This study examined age differences in task switching using prosaccade and antisaccade tasks. Significant specific and general switch costs were found for both young and old adults, suggesting the existence of 2 types of processes: those responsible for activation of the currently relevant task set and deactivation of the previously relevant task set and those responsible for maintaining more than 1 task active in working memory. Contrary to the findings of previous research, which used manual response tasks with arbitrary stimulus-response mappings to study task-switching performance, no age-related deficits in either type of switch costs were found. These data suggest age-related sparing of task-switching processes in situations in which memory load is low and stimulus-response mappings are well learned.     

Collective Narcissism as a Basis for Nationalism

Recent work suggests that collective narcissism—an exaggerated, unrealistic belief in an ingroup's greatness that demands constant external validation—is a strong predictor of a variety of political attitudes. In the present study, we use nationally representative panel data from Poland to examine the relationship between national collective narcissism and nationalism, a belief that the national ingroup is superior and should dominate other nations. We first demonstrate that national collective narcissism, nationalism, and mere satisfaction with national ingroup are distinct. In turn, in both cross-sectional and panel analyses, we find that (1) national collective narcissism is positively related to nationalism, whereas satisfaction with the national ingroup is not; and (2) national collective narcissism is a stronger predictor of nationalism than national ingroup satisfaction is in absolute terms. Our analyses thus provide evidence that nationalism may be rooted in narcissistic exaggeration of the greatness of the national ingroup rather than nonnarcissistic national ingroup satisfaction.     

Próba uporządkowania podstawowego słownictwa prawniczego

Allatum est die 3 Junii 1963     

Emergency Research without Consent under Polish Law

Although Directive 2001/20/EC of the European Parliament and of Council of 4 April 2001 on the approximation of the laws regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use does not contain an exception for emergency situations, and requires the informed consent of a legal representative in all cases where research is conducted on legally competent individuals who are unable to give informed consent, in Poland, emergency research can be conducted without consent. Polish regulations on emergency research can hardly be treated as a result of intentional legislative policy. Our provisions arise from multiple and sophisticated interpretations of different regulations that govern medical experiments on human subjects and clinical trials. These interpretations can be summarized as follows: (1) There are two categories of medical experiments: therapeutic and non-therapeutic experiments. Emergency research without consent may be conducted in the category of therapeutic experiment only (therapeutic experiment consists of the introduction by the physician of new or only partially proven diagnostic, therapeutic or preventive methods in order to achieve direct benefit to the health of the patients, and it can be carried out when hitherto applied methods were ineffective or their effectiveness was insufficient). (2). Emergency research may be conducted without consent if there is a situation of great urgency in which the research subject's life is in danger and there is no possibility of obtaining immediate consent from the research subject him or herself, or from his or her legal representative or guardianship court, and the research subject has not refused to give consent for the participation in an emergency therapeutic experiment. The legal representative or guardianship court shall be provided with all the relevant information concerning subject's participation in an experiment as soon as possible. All projects of emergency research with intent to be done without the research subject's consent must be approved by an independent bioethics committee. Because these five requirements seem to provide insufficient protection for a subject's autonomy and rights it is necessary to add to them two other conditions: (1) the emergency research could not be conducted using other research participants capable of giving informed consent; and (2) informed consent for continued participation in the emergency research shall be obtained from either the participant him or herself or the legally authorized representative as soon as possible (requirement of obtaining deferred consent). A consolidated single Act that will govern all aspects of medical experiments on human subjects, including emergency research, should be prepared and enacted as soon as possible.