Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

BackgroundPublic Safety Personnel are routinely exposed to human suffering and need to make quick, morally challenging decisions. Such decisions can affect their psychological wellbeing. Participating in or observing an event or situation that conflicts with personal values can potentially lead to the development of moral injury. Common stressors associated with moral injury include betrayal, inability to prevent death or harm, and ethical dilemmas. Potentially psychologically traumatic event exposures and post-traumatic stress disorder can be comorbid with moral injury; however, moral injury (...) extends beyond fear to include spiritual, cognitive, emotional or existential struggles, which can produce feelings of severe shame, guilt, and anger.ObjectiveThis scoping review was designed to identify the extant empirical research regarding the construct of moral injury, its associated constructs, and how it relates to moral distress in firefighters, paramedics, and police officers.MethodsA systematic literature search of peer-reviewed research was conducted using databases MEDLINE, EMBASE, APA PsychInfo, CINHAL PLUS, Web of Science, SCOPUS, and Google Scholar. Included studies were selected based on the inclusion criteria before being manually extracted and independently screened by two reviewers.ResultsThe initial database search returned 777 articles, 506 of which remained after removal of duplicates. Following review of titles, abstracts, and full texts, 32 studies were included in the current review. Participants in the articles were primarily police officers, with fewer articles focusing on paramedics and firefighters. There were two studies that included mixed populations. Most studies were qualitative and focused on four topics: values, ethical decision-making, organizational betrayal, and spirituality.ConclusionPublic safety organizations appear to recognize the experience of moral distress or moral injury among public safety personnel that results from disconnects between personal core values, formal and informal organizational values, vocational duties, and expectations. Further research is needed to better understand moral distress or moral injury specific to public safety personnel and inform training and treatment in support of public safety personnel mental health. (shrink)

Neuroethics entails investigations of neurocognitive mechanisms of morality and ethics; and studies and address of the ethical issues spawned by the use of neuroscience and its technologies to investigate cognition, emotion and actions. These two principal emphases, or what have been called “traditions” of neuroethics both mirror traditional bioethical discussions (such as debates about the safety of technological and pharmaceutical advances and ethical implications of new scientific and technological discoveries), and engage discourse about neuroscientific investigations of (proto-moral and moral) cognition, (...) emotions and behaviors, and what such findings may mean for human beliefs and conduct - from the individual to the political levels. (shrink)

Paperwork plays a key role in a how institutions accommodate, refuse, or manage disabled people. This article develops modes for reading paperwork that build on each other, beginning with (a) recognizing the institutional pressures at work in shaping bureaucratic practices, then (b) considering how a person's relationship to disability influences how they might encounter these practices, and ultimately (c) noticing how the encounter between disabled/mad people and an institution might create something new, what the author calls archival excess. These methods (...) for reading are in conversation with disability studies, medical humanities, and document studies, and ultimately work toward a goal adapted from the principles of Disability Justice: recognizing the wholeness of disabled subjects in institutional archives. (shrink)

The boundaries, openness and character of the future European society will crucially depend on the degree and scope of identity politics. Religion, culture and nationality remain strong reference frameworks for individuals in their inter-personal but also political relations and tend, in practice, to favour weak rather than strong forms of citizenship. Whether this is a viable model for large and diverse democratic societies is an old debate known primarily from the discussions and theory on multiculturalism. How this debate is played (...) out at European level and especially with respect to the role of religion is illustrated with reference to the ideas of Daniel Cohn-Bendit and Tariq Ramadan, two well-known public figures with a strong commitment to Europe and European identity, albeit from rather different perspectives and outlooks. At the substantive or philosophical level, it appears impossible to resolve the fundamental questions underlying the opposition between liberalism and communitarianism as represented by the two men. The usefulness of a middle-range pragmatic approach insofar as political solutions or societal compromises are concerned is scrutinized for its usefulness. (shrink)

This article, based on grandparents' narratives collected in a doctoral research project, aims to weave together reflections on childhood, intergenerational bonding, and love. Seven grandmothers and three grandfathers, between fifty-one and seventy-one years old, participated in the research; nine residents of the city of Rio de Janeiro and one of Niterói, Brazil. In addition, narratives were collected from six of their grandchildren, all of them between five and twelve years old, and residents of Rio de Janeiro, Niterói, Brasília and Montevideo, (...) Uruguay. Conducted during the Covid-19 pandemic, our methodological strategy involved interviews conducted on Zoom. Interviews with the adults were conducted individually, and collectively with the children. The themes that emerged in the grandparents' narratives led to reflections on the relationship between adults and children that are emblematic of the conception of childhood found in Walter Benjamin's work, as well as the philosophical anthropology of Martin Buber and the psychoanalysis of Donald Winnicott. The emphasis of the research participants was on affective security, built on the basis of small, everyday gestures, which result in an atmosphere of mutual support between children and adults. From these affectionate encounters between the youngest and the oldest, what we characterize as a “childlike force” is established—an energy field that produces new existential possibilities. The narratives collected here teach us new ways of being adult through our relationships with children: in our encounter with the lifeworlds of the youngest among us, we re-encounter our own deeper sensibilities, and regain the ability to play, to create, and to reinvent ourselves in relearning the joy of beginnings. (shrink)

The lack of access to gender-affirming surgery represents a significant unmet health care need within the transgender community, frequently resulting in depression and self-destructive behavior. While some transgender people may have access to gender reassignment surgery, an overwhelming majority cannot afford facial feminization surgery. The former may be covered as a “medical necessity,” but FFS is considered “cosmetic” and excluded from insurance coverage. This demarcation between “necessity” and “cosmetic” in transgender health care based on specific body parts is in direct (...) opposition to the scientific community’s understanding of gender dysphoria and professional guidelines for transgender health. GRS affects one’s ability to function in an intimate relationship, while FFS has the same impact on social interactions an, therefore may have a far greater implication for one’s quality of life. FFS is a cost-effective intervention that needs to be covered by insurance policies. The benefits of such coverage far exceed the insignificant costs. (shrink)

Since its inception, modern anthropology has stood at the confluence of two mutually constitutive modes of knowledge production: participant-observation and theoretical analysis. This unique combination of practice and theory has been the subject of recurrent intellectual and methodological debate, raising questions that strike at the very heart of the discipline. How Do We Know? is a timely contribution to emerging debates that seek to understand this relationship through the theme of evidence. Incorporating a diverse selection of case studies ranging from (...) the Tibetan emotion of shame to films of Caribbean musicians, it critically addresses such questions as: What constitutes viable anthropological evidence? How does evidence generated through small-scale, intensive periods of participant-observation challenge or engender abstract theoretical models? Are certain types of evidence inherently better than others? How have recent interdisciplinary collaborations and technological innovations altered the shape of anthropological evidence? Extending a long-standing tradition of reflexivity within the discipline, the contributions to this volume are ethnographically-grounded and analytically ambitious meditations on the theme of evidence. Cumulatively, they challenge the boundaries of what anthropologists recognise and construct as evidence, while pointing to its thematic and conceptual potential in future anthropologies. (shrink)

The Arabic original of the ninth-century Kitāb al-Nawāmīs has not been discovered, save for three incomplete chapters. We have access to a fuller version only through a Latin translation, often known as the Liber vaccae, a title derived from its notorious experiments which involve the gruesome slaughter and mutilation of a cow to magically produce a rational animal or bees. Recent research on the Liber vaccae has focused mostly on its reception in medieval and early modern Europe. By contrast, the (...) present article explores the Indo-Arabic tradition to which Kitāb al-Nawāmīs belongs, as a re-orientation of the Liber vaccae established on two levels: textual and theoretical. Section I, on 'Texts and Practices', introduces ʿUyūn al-ḥaqāʾiq of Abū al-Qāsim al-ʿIrāqī, a text on magical practices which contains 26 chapters that correspond to sections in the Liber vaccae, affording us a glance into the Arabic reception of Kitāb al-Nawāmīs and bringing us closer to the Arabic original. The textual connection is established further by highlighting parallels between the experiments of the Liber vaccae / Kitāb al-Nawāmīs and other texts on natural magic, namely Ghāyat al-ḥakīm of Maslama al-Qurṭubī and Kitāb al-Sumūm by Ibn Waḥshiyya. Section II investigates the theoretical bases of the Liber vaccae / Kitāb al-Nawāmīs, by associating its content with the theories of spontaneous and artificial generation in Kitāb al-Tajmīʿ attributed to Jābir ibn Hayyān, Ghāyat al-ḥakīm, Kitāb al-Sumūm and, finally, another work by Ibn Waḥshiyya, al-Filāḥa al-nabaṭiyya. Jābir's and al-Qurṭubī's works have been studied in relation to the Liber vaccae by David Pingree, Maaike Van der Lugt, Sophie Page and William Newman; their findings are re-evaluated here in light of the texts of Ibn Waḥshiyya and al-ʿIrāqī. (shrink)

У статті розглянуті методологічні підходи до визначення сутності та критеріїв класифікації економічних систем. У різноманітті підходів до класифікації економічних систем виділені два основних - формаційний та цивілізаційний. Проаналізовано погляди вчених на співвідношення цих підходів. Аргументована некоректність постановки питання про необхідність доповнити формаційні критерії цивілізаційними критеріями.

There is a need to consider the impact of the new resident-hours regulations on the variety of aspects of medical education and patient care. Most existing literature about this subject has focused on the role of fatigue in resident performance, education, and health care delivery. However, there are other possible consequences of these new regulations, including a negative impact on decision ownership. Our main assumption of is that increased shift work in medicine can decrease ownership of treatment decisions and impact (...) negatively on quality of care. We review some potential components of decision ownership in treatment context and suggest possible ways in which the absence of decision ownership may decrease the quality of medical decision making. The article opens with the definition of decision ownership and the overview of some contextual factors that may contribute to the development of ownership in medical residency. The following section discusses decision ownership in medical care from the perspe... (shrink)

_Islamicate Occult Sciences in Theory and Practice_ presents the latest research on Islamic occult sciences from a variety of disciplinary perspectives, namely intellectual history, manuscript studies and material culture.

Fighting ability, although recognized as fundamental to intrasexual competition in many nonhuman species, has received little attention as an explanatory variable in the social sciences. Multiple lines of evidence from archaeology, criminology, anthropology, physiology, and psychology suggest that fighting ability was a crucial aspect of intrasexual competition for ancestral human males, and this has contributed to the evolution of numerous physical and psychological sex differences. Because fighting ability was relevant to many domains of interaction, male psychology should have evolved such (...) that a man’s attitudes and behavioral responses are calibrated according to his formidability. Data are reviewed showing that better fighters feel entitled to better outcomes, set lower thresholds for anger/aggression, have self-favoring political attitudes, and believe more in the utility of warfare. New data are presented showing that among Hollywood actors, those selected for their physical strength (i.e., action stars) are more likely to believe in the utility of warfare. (shrink)

The concept of a G‐quartet, a unique structural arrangement intrinsic to guanine‐rich DNA, was first introduced by Gellert and colleagues1 over 40 years ago. For decades, it has been uncertain whether the G‐quartet and the structure that it gives rise to, the G‐quadruplex, are purely in vitro phenomena. Nevertheless, the presence of signature G‐rich motifs in the eukaryotic genome, and the plethora of proteins that bind to, modify or resolve this nucleic acid structure in vitro have provided circumstantial evidence for (...) its physiological relevance. More recently, direct visualisation of G‐quadruplex DNA at native telomeres was achieved, bolstering the evidence for its existence in the cell. Furthermore, G‐quadruplex folded telomeric DNA has been found to perturb telomere function and to impede the action of telomerase, an enzyme overexpressed in >85% of human cancers, hence opening up a novel avenue for cancer therapy in the form of G‐quadruplex stabilising agents. BioEssays 29: 155–165, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Philosophical interests of Joseph Życiński in the domain of the philosophy of science were focused on the debate concerning the nature of science and philosophy of science that followed the Einstein-Planck revolution in science. The unexpected discovery of the philosophical, extra-scientific presuppositions in science, as well as of the extra-rational factors determining the way these presuppositions are accepted in science were to be explained within the meta-scientific framework. It is the aim of this paper to present ˙ Życiński’s diagnosis of (...) this post-revolutionary situation in the philosophy of science as well as his critique of the metascientific answers to this challenge. The reasons will be given why all those answers are put under two dichotomous rubrics of _internalism_ and _externalism_. It will be also explained how Życiński intends to supersede this false in his opinion opposition with a new concept of the doxatic rationality. However, the details of the metascientific proposal of Życiński will be given only in the subsequent paper. In order to perform the aim of the paper the metatheoretic tools set out by Popper will be used. (shrink)

The author discusses the meaning of the paradox, which rises as a result of the controversy between the principles of scientific ethos (R. Merton) and fallibilism (K. Popper). She argues that the justification of the moral authority of science should not depend on this paradox. The author uses Max Weber’s concept of substantive rationality to consider the idea of social legitimation of science. She argues for understanding expertise as a special mode of scientific knowledge which aims at justifying the authority (...) of science in the society. (shrink)

Engineering failure investigations seek to reconstruct the actual causes of major engineering failures. The investigators need to establish the existence of certain past events and the actual causal relationships that these events bear to the failures in question. In this paper, I examine one method for reconstructing the actual causes of failure events, which I call "feature dependence". The basic idea of feature dependence is that some features of an event are informative about the features of its causes; therefore, the (...) investigators can use the features of a known failure event to reconstruct details of its causes. I make explicit the structure of feature dependence and the evidential basis of its key premises, and show how feature dependence works in the investigation of the American Airlines Flight 191 accident. (shrink)

One of the main problems of modern rationalistic theories of science is the non-eliminability of the subjective factor in the development of science. Temperate rationalism of Newton-Smith was an attempt to solve this problem. J. Życiński developed his own version of temperate rationalism in which the subjective factor played much more substantial role. In the article I am presenting his specific idea of the personal _commitment_ as a necessary condition for rationalism and science. In the first section I proceed to (...) reconstruct ˙ Życiński’s argument leading him to the conclusion of this epistemological necessity. Next in the section 2 I present his idea of the epistemological uncertainty principle as a consequence of the subjective _commitment_. In sections 3 and 4 I explore axiological and pragmatic aspects of the Życiński solution. Finally, in the section 5 I do compare his temperate rationalism with Newton-Smith’s proposal in the context of the Polanyi’s idea of personal knowledge showing differences in their respective approach to the role of the subjective factor in science and rationalism. (shrink)

The author analyzes the phenomenon of denialism (denial of scientific consensus out of the normative boundaries of scientific discussion). The intellectual origins (including connection with P. Feyerabend’s post-positivism), sociocultural characteristics and political aspects of this phenomenon are discussed. The author defends the thesis that denialism is associated with scientism – non-reflexive trust in science, which is used for unscrupulous manipulations for the purpose of political influence. As an example, she considers the South African expert case related to HIV denial in (...) the early 2000s. The author believes that denialism needs a comprehensive analysis that takes into account the interdependence of its intellectual and socio-political foundations. (shrink)

The article reconstructs the premises of the reception of analytic philosophy in jurisprudence and shows that the development of a method for clarifying the meanings of legal concepts is not least connected with the problem of legitimizing law enforcement. The article analyzes H.L.A. Hart’s approach to the problem of correlation between the “letter” and “spirit” of the law in the process of interpreting legal norms. The article argues that the process of interpretation is determined teleologically. In its limit, the interpretation (...) of legal norms presupposes the re-creation of the desired image of society, the reconstruction of such social ontology that is most consistent with the ideal of achieving social welfare. The article examines the collision of the “ideal of order” and the “ideal of justice” as two regulations of law enforcement. The author believes that the interpretation of this collision within the analytical tradition was characterized by a gradual movement from the ideal of “mechanical” law enforcement, which minimizes the creative role of the interpreter, to the ideal of flexible interpretation focused on achieving legal goals in a changing environment. It is noted that, according to analytic approach, a theoretical solution to this conflict was proposed due to the development of the ideas of an “open texture” of law. The author demonstrates that the development of the analytic tradition in jurisprudence has shown that the criticism of language and the interpretation of meanings are not technical tasks, but it presupposes the construction of a metaphysics of law. In this regard, the author concludes: the development of the ideas of the analytic tradition in jurisprudence demonstrates that the thesis about the absence of a positive program in analytic philosophy, put forward in the first article of the discussion, can be challenged. (shrink)

This is a review of the book “The Future of Law and Economics” by American legal philosopher and judge Guido Calabresi (Moscow: Institut Gaidara, 2016). Author considers the theoretical aspects of the bilateral relations between the economic theory and legal studies developed by Calabresi. The author analyzes the differences between the previous tradition of the economic approach to law, which was based on the principle of epistemological expansion of economic theory into the field of legal studies, and the common program (...) of “law and economic”, which is aimed to find the basis for the bilateral dialogue between these sides of social knowledge. Both programs assume some alternatives for the formal analysis of law. The author discusses the concept of merit good and evaluates the prospects for the reception of this concept in legal philosophy. (shrink)

The author advocates the idea about the connection between the spirit of early Victorian England and the birth of philosophy of science. She pays special attention to the arguments provided by W. Whewell in support of “the scientific turn” of English university education. The author argues that the public intellectual discussions organized by the leading English daily magazines (i.e. Tatler, Spectator) played their role the formation of the public sphere (J. Habermas) in this period. These discussions contributed to the search (...) for a normative consensus between the bourgeoisie and the land aristocracy. (shrink)

Noted logician and philosopher addresses various forms of mathematical logic, discussing both theoretical underpinnings and practical applications. After historical survey, lucid treatment of set theory, model theory, recursion theory and constructivism and proof theory. Place of problems in development of theories of logic, logic’s relationship to computer science, more. Suitable for readers at many levels of mathematical sophistication. 3 appendixes. Bibliography. 1981 edition.