Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing

The importance of proper mutational analysis of BRCA1/2 in individuals at risk for hereditary breast and ovarian cancer syndrome is widely accepted. Standard genetic screening includes targeted analysis of recurrent, population-specific mutations. The purpose of the study was to establish the frequency of germline BRCA1/2 mutations in a group of 134 unrelated patients with primary ovarian cancer. Next generation sequencing analysis revealed a presence of 20 (14.9 %) mutations, where 65 % (n = 13) were recurrent BRCA1 alterations included in the standard diagnostic panel in northern Poland. However, the remaining seven BRCA1/2 mutations (35 %) would be missed by the standard approach and were detected in unique patients. A substantial proportion (n = 5/12; 41 %) of mutation-positive individuals with complete family history reported no incidence of breast or ovarian cancer in their relatives. This observation, together with the raising perspectives for personalized therapy targeting BRCA1/2 signaling pathways indicates the necessity of comprehensive genetic screening in all ovarian cancer patients. However, due to the limited sensitivity of the standard genetic screening presented in this study (65 %) an application of next generation sequencing in molecular diagnostics of BRCA1/2 genes should be considered

Sobre tû-tû

The goal of this short paper is to argue that so-called intermediary concepts play an essential role in organizing and generating legal knowledge. The point of departure is a reconstruction and a critique of Alf Ross’s analysis of such concepts. His goal was to argue that there exist concepts in the law which have no semantic reference, yet it is reasonable to use them as they perform some useful function regarding the presentation of legal rules. The author believes that Ross is wrong on both counts: his argument to the effect that intermediary concepts have no reference is flawed, and his characterization of the functions such concepts play in the law is too limiting.El propósito en este breve artículo es argumentar que los llamados conceptos intermediarios juegan un rol esencial en la organización y generación del conocimiento jurídico. El punto de partida es una reconstrucción y crítica del análisis de Alf Ross sobre dichos conceptos. Su objetivo era argumentar que existen conceptos en el derecho que no tienen referencia semántica, pero que aun así es razonable usarlos dado que cumplen con algunas funciones útiles relacionadas con la presentación de las reglas jurídicas. El autor de este artículo afirma que Ross está equivocado en ambos casos: su argumento al efecto de que los conceptos intermediarios no tienen referencia es defectuoso, y su caracterización de las funciones que dichos conceptos cumplen en el derecho es muy limitante

On tû-tû

The goal in this short paper is to argue that so-called intermediary concepts play an essential role in organizing and generating legal knowledge. The point of departure is a reconstruction and a critique of Alf Ross’s analysis of such concepts. His goal was to argue that there exist concepts in the law which have no semantic reference, yet it is reasonable to use them as they perform some useful function regarding the presentation of legal rules. The author believes that Ross is wrong on both counts: his argument to the effect that intermediary concepts have no reference is flawed, and his characterization of the functions such concepts play in the law is too limiting

Introduction: Between law and the cognitive sciences - A manifesto

This commentary examines the issue of judicial bias in response to the chapter, The Psychology of the Trial Judge, by Morris Hoffman. With a focus on retributive punishment judgments, it questions whether human decision makers, including judges, can rely on their powers of rationality, or whether such judgments are fundamentally emotional and intuitive. I begin with the observation that we, as a society, do not have a clear conceptual understanding of why we punish criminals. Further, there are good reasons to think that retributive attitudes might be the expression of psychological biases, and this poses problems for the prospect of rational punishment. At the least, a coherent justification for punishment should be informed by an empirical understanding of the causes of these psychological biases, including their evolutionary origins. Evolutionary scholarship suggests that retributive attitudes evolved to generate consequentialist outcomes like deterrence, but they did so to achieve a competitive advantage between individuals, not to protect society as a whole. Such findings suggest that our retributive attitudes today might not always function in ways that are best for society. Thus, understanding why our punishment psychology evolved in the ways that it did, we as a society can more cogently evaluate whether we embrace those reasons or reject them. An appreciation of our evolved psychology of punishment can also provide a framework for unifying the rival legal justifications for punishment. From this perspective, retributive and consequentialist motives for punishment are not completely incompatible. Rather, they are different levels of analysis for describing our universal punishment psychology

Are the cognitive sciences relevant for law?

This chapter addresses the question of whether the cognitive sciences are relevant for law. The answer to this question will turn out to be a threefold ‘yes’. First, if law is traditionally conceived as a set of rules that prescribe what ought to be done, there is a role for the cognitive sciences in determining the facts of the cases to which the law is to be applied (evidential reasoning). Legal decision making often involves the application of open-textured concepts, and the cognitive sciences can study the psychological processes and perhaps also the biases involved in such an application. Moreover, the results of the cognitive sciences may also be important for the evaluation of law, and for determining what good law might be. A perhaps more ambitious role for cognitive sciences in law has to do with the determination of the content of the law. If law is a social phenomenon, and if social phenomena depend on what goes on in human minds, cognitive sciences can, at least in theory, study the content of the law. Some would argue that the cognitive sciences could never fulfil this more ambitious role, because law has to do with what OUGHT to be done, or ought to be the case, while sciences, including cognitive sciences, can only study what IS the case. It will be argued that this fundamental objection against this role for the cognitive sciences is misguided: there is no hard difference between IS and OUGHT and even if law belongs to the realm of OUGHT, cognitive sciences may still be relevant for determining the content of the law. Finally, the cognitive sciences may disrupt the image of humankind that underlies law. It turns out that people are less rational than they may seem at first glance, that they often do not know what motivates them, that it is not obvious what actions and agents are and that it is unclear what the best level of explanation is for human actions or bodily movements. A change in the image of humankind that underlies law, to reflect the recent insights of the cognitive sciences but also of ancient philosophical debates, may have important consequences for the contents of law

The insanity defense

Legal insanity is an element of many legal systems, and it has often stirred debate. It appears that many are intrigued by this defense, which touches upon a variety of enigmatic subjects, such as severe crimes, fairness, free will, retribution, and the reliability of expert testimony. In this chapter, key questions regarding the insanity defense will be considered. Why should insanity be part of our legal system? What should be the criteria for legal insanity? Can neuroscience help to assess a defendant’s sanity? Since legal insanity lies at the interface of law and psychiatry, we will have to consider both legal and psychiatric matters. As we are interested in the foundations of legal insanity, we will take moral philosophy into account as well. First, we consider some arguments pro and con the insanity defense. This implies addressing certain challenges regarding psychiatric assessments, such as the fact that it concerns a past mental state, and the risk that defendants will malinger (faking bad) or hide their symptoms (faking good). Second, we will examine the components of several legal standards for insanity such as the M’Naghten Rule and the Model Penal Code test. Third, the idea that the defense relies on the possibility that a mental illness may compromise a person’s free will will be discussed. I will conclude that the notion of “free will” provides at best a partial justification for legal insanity. Many legal systems define a specific threshold of proof for insanity, for instance, “by a preponderance of the evidence.” We concisely consider the burden of proof, in particular the threshold of proof. Next, the ethics of forensic psychiatric assessment and testimony about a defendant’s insanity will be discussed. Since forensic psychiatric evaluations of defendants do not take place in a therapeutic doctor–patient relationship, the ethical context is also different from the standard healthcare setting. Finally, the role of neuroimaging in insanity evaluations will be considered

The insanity defense

Legal insanity is an element of many legal systems, and it has often stirred debate. It appears that many are intrigued by this defense, which touches upon a variety of enigmatic subjects, such as severe crimes, fairness, free will, retribution, and the reliability of expert testimony. In this chapter, key questions regarding the insanity defense will be considered. Why should insanity be part of our legal system? What should be the criteria for legal insanity? Can neuroscience help to assess a defendant’s sanity? Since legal insanity lies at the interface of law and psychiatry, we will have to consider both legal and psychiatric matters. As we are interested in the foundations of legal insanity, we will take moral philosophy into account as well. First, we consider some arguments pro and con the insanity defense. This implies addressing certain challenges regarding psychiatric assessments, such as the fact that it concerns a past mental state, and the risk that defendants will malinger (faking bad) or hide their symptoms (faking good). Second, we will examine the components of several legal standards for insanity such as the M’Naghten Rule and the Model Penal Code test. Third, the idea that the defense relies on the possibility that a mental illness may compromise a person’s free will will be discussed. I will conclude that the notion of “free will” provides at best a partial justification for legal insanity. Many legal systems define a specific threshold of proof for insanity, for instance, “by a preponderance of the evidence.” We concisely consider the burden of proof, in particular the threshold of proof. Next, the ethics of forensic psychiatric assessment and testimony about a defendant’s insanity will be discussed. Since forensic psychiatric evaluations of defendants do not take place in a therapeutic doctor–patient relationship, the ethical context is also different from the standard healthcare setting. Finally, the role of neuroimaging in insanity evaluations will be considered