The Krüppel‐like factors (KLFs) comprise a family of evolutionarily conserved zinc finger transcription factors that regulate numerous biological processes including proliferation, differentiation, development and apoptosis. KLF4 and KLF5 are two closely related members of this family and are both highly expressed in epithelial tissues. In the intestinal epithelium, KLF4 is expressed in terminally differentiated epithelial cells at the villus borders of the mucosa and inhibits cell growth, while KLF5 is expressed in proliferating epithelial cells at the base of the intestinal (...) crypts and promotes cell growth. KLF4 and KLF5 respond to a myriad of external stress stimuli and are likely involved in restoring cellular homeostasis following exposure to stressors. Confirming their importance in maintaining tissue integrity, KLF4 and KLF5 are both dysregulated in various types of cancer. Here we review the recent advances in defining the physiological and pathobiological roles of KLF4 and KLF5, focusing on their functions in the intestinal epithelium. BioEssays 29:549–557, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Increased productivity may have negative impacts on farm animal welfare in modern animal production systems. Efficiency gains in production are primarily thought to be due to the intensification of production, and this has been associated with an increased incidence of production diseases, which can negatively impact upon FAW. While there is a considerable body of research into consumer attitudes towards FAW, the extent to which this relates specifically to a reduction in production diseases in intensive systems, and whether the increased (...) incidence of diseases represents a barrier to consumer acceptance of their increased use, requires further investigation. Therefore a systematic review of public attitudes towards FAW was conducted, with a specific focus on production diseases in intensive systems. Four databases were searched to identify relevant studies. A screening process, using a set of pre-determined inclusion criteria, identified 80 studies, with the strength of evidence and uncertainty assessed for each. A thematic analysis led to the identification of 6 overarching themes constructed from 15 subthemes. The results demonstrate that the public are concerned about FAW in modern production systems. Concern varied in relation to age, gender, education and familiarity with farming. Naturalness and humane treatment were central to what was considered good welfare. An evidence gap was highlighted in relation to attitudes towards specific production diseases, with no studies specifically addressing this. However, the prophylactic use of antibiotics was identified as a concern. A number of dissonance strategies were adopted by consumers to enable guilt free meat consumption. (shrink)

The current rise of neurodevelopmental disorders poses a critical need to detect risk early in order to rapidly intervene. One of the tools pediatricians use to track development is the standard growth chart. The growth charts are somewhat limited in predicting possible neurodevelopmental issues. They rely on linear models and assumptions of normality for physical growth data – obscuring key statistical information about possible neurodevelopmental risk in growth data that actually has accelerated, non-linear rates-of-change and variability encompassing skewed distributions. Here, (...) we use new analytics to profile growth data from 36 newborn babies that were tracked longitudinally for 5 months. By switching to incremental (velocity-based) growth charts and combining these dynamic changes with underlying fluctuations in motor performance – as the transition from spontaneous random noise to a systematic signal – we demonstrate a method to detect very early stunting in the development of voluntary neuromotor control and to flag risk of neurodevelopmental derail. (shrink)

Tobacco mosaic virus has served as a model organism for pathbreaking work in plant pathology, virology, biochemistry and applied genetics for more than a century. We were intrigued by a photograph published in Phytopathology in 1934 showing that Tabasco pepper plants responded to TMV infection with localized necrotic lesions, followed by abscission of the inoculated leaves. This dramatic outcome of a biological response to infection observed by Francis O. Holmes, a virologist at the Rockefeller Institute for Medical Research, was used (...) to score plants for resistance to TMV infection. Our objective was to gain a better understanding of early to mid-twentieth century ideas of genetic resistance to viruses in crop plants. We investigated Holmes’ observation as a practical exercise in reworking an experiment, having been inspired by Pamela Smith’s innovative Making and Knowing Project. We had a great deal of difficulty replicating Holmes’ experiment, finding that biological materials and experimental customs change over time, in ways that ideas do not. Using complementary tools plus careful study and interpretation of the original text and figures, we were able to rework, yet only partially replicate, this experiment. Reading peer-reviewed manuscripts that cited Holmes’ 1934 report provided an additional level of insight into the interpretation and replication of this work in the decades that followed. From this, we touch on how experimental reworking can inform our strategies to address the reproducibility “crisis” in twenty-first century science. (shrink)

This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non‐validated or hypothesis‐generating). There is, however, a trend for research participants to be permitted (...) access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico‐legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer ‘Points‐to‐Consider’ regarding returning research results in the context of drug development trials based on their knowledge and experience. These considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit‐to‐risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies. (shrink)

ABSTRACT This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non‐validated or hypothesis‐generating). There is, however, a trend for research participants to be (...) permitted access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico‐legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer ‘Points‐to‐Consider’ regarding returning research results in the context of drug development trials based on their knowledge and experience. These considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit‐to‐risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies. (shrink)

Objective:Prior research examining sexual and intimacy concerns among metastatic breast cancer patients and their intimate partners is limited. In this qualitative study, we explored MBC patients’ and partners’ experiences of sexual and intimacy-related changes and concerns, coping efforts, and information needs and intervention preferences, with a focus on identifying how the context of MBC shapes these experiences.Methods:We conducted 3 focus groups with partnered patients with MBC [N = 12; M age = 50.2; 92% White; 8% Black] and 6 interviews with (...) intimate partners [M age = 47.3; 83% White; 17% Black]. Participants were recruited through the Fox Chase Cancer Center Tumor Registry and the Cancer Support Community. Qualitative data were analyzed using the Framework Method and Dedoose software.Results:Qualitative analyses revealed several key themes reflecting ways in which MBC shapes experiences of sex/intimacy: the heavy disease/treatment burden leads to significant, long-term sexual concerns and consequent heightened emotional distress for both patients and partners ; viewing the relationship as having “an expiration date” influences patients’ and partners’ concerns related to sex/intimacy and complicates coping efforts; and information needs extend beyond managing sexual side effects to include emotional aspects of intimacy and the added strain of the life-limiting nature of the disease on the relationship. The heightened severity of sexual concerns faced by patients with MBC, compounded by the terminal nature of the disease, may place patients and partners at risk for significant adverse emotional and interpersonal consequences.Conclusion:Findings suggest unique ways in which sex and intimate relationships change after a diagnosis of metastatic breast cancer from both patients’ and partners’ perspectives. Consideration of the substantial physical and emotional burden of MBC and the broader context of the relationship and intimacy overall is important when developing a sexuality-focused intervention in this population. Addressing sexual concerns is a critical part of cancer care with important implications for patients’ health and quality of life. (shrink)

This paper examines Spinoza's remarks on women in the Political Treatise in the context of his views in the Ethics about human community and similitude. Although these remarks appear to exclude women from democratic participation on the basis of essential incapacities, I aim to show that Spinoza intended these remarks not as true statements, but as prompts for critical consideration of the place of women in the progressive democratic polity. In common with other scholars, I argue that women, in Spinoza's (...) system, are deprived of freedom and political participation not by their essential natures, but by their social and historical circumstances. I differ from other scholars, however, in basing this conclusion on the different critical functions of the Political Treatise and the Ethics. Following that critical comparison, I consider Spinoza's views on the `natural right' of women and their equal capacity for political participation in terms of his arguments for the compositional similarity of men and women. Finally, I argue that Spinoza offers an explanation for women's actual disempowerment through his account of economic dependence within marriage. (shrink)

A version of this paper was first presented at the conference The Radical Enlightenment: the Big Picture and its Details in Brussels in May 2013. I would like to thank Steffen Ducheyne and the organizing team at the Vrije Universiteit Brussel, and to acknowledge the many helpful comments I received from listeners there and at subsequent events. Thanks also to the anonymous reviewer who suggested several helpful refinements.

Beth Lord explores Spinoza’s rejection of natural moral equality and its relevance for modern democracy.

(2011). Spinoza and the Specters of Modernity: The Hidden Enlightenment of Diversity from Spinoza to Freud. British Journal for the History of Philosophy: Vol. 19, No. 2, pp. 339-342.

SummaryThe germs of future development, contained in Aristotle's logical works, are indicated, and their influence on the later evolution of logic is explained.The history of symbolic logic since Boole's Mathematical analysis and De Morgan's Formal logic, both of which were published in 1847, is divided into four approximately subsequent phases, viz.:1. algebra of logic; this phase is characterized by Boole's work;2. logical foundation of mathematics; this phase is characterized by Frege's, Peano's and Russell's work, by the discovery of the antonomies (...) of logic and set theory, by the Couturat‐Poincaré debate and by the rise of Brouwer's intuitionism;3. intuitive metamathematics, concentrating in Hilbert's attempts towards a consistency proof for classical analysis; the discovery of Gödel's theorem necessitated a change of policy;4. axiomatic methodology, deriving from Hilbert's metamathematics and culminating so far in Tarski's semantics. — E. W. B. (shrink)

The debate over foundationalism, the viewpoint that there exists some secure foundation upon which to build a system of knowledge, appears to have been resolved and the antifoundationalists have at least temporarily prevailed. From a firmly historical approach, the book traces the foundationalism/antifoundationalism controversy in the work of many important figures Animaxander, Aristotle and Plato, Augustine, Descartes, Hegel and Nietzsche, Habermas and Chisholm, and others throughout the history of philosophy. The contributors, Joseph Margolis, Ronald Polansky, Gary Calore, Fred and Emily (...) Michael, William Wurzer, Charlene Haddock Siegfried, Sandra B. Rosenthal, Kathleen Wallace, and the editors present well the diversity, interest, and roots of antifoundationalism. Tom Rockmore is Professor and Chairman in the Department of Philosophy at Duquesne University. Beth J. Singer is Professor of Philosophy at Brooklyn College of the City University of New York. (shrink)

Our goal in producing this special issue is to encourage our colleagues to incorporate topics related to LGBT populations into bioethics curricula and scholarship. Bioethics has only rarely examined the ways in which law and medicine have defined, regulated, and often oppressed sexual minorities. This is an error on the part of bioethics. Medicine and law have served in the past as society's enforcement arm toward sexual minorities, in ways that robbed many people of their dignity. We feel that bioethics (...) has an obligation to discuss that history and to help us as a society take responsibility for it.We can address only a small number of topics in this special issue of the Hastings Center Report, and we selected topics we believe will stimulate discourse. Andrew Solomon offers an elegant overview of the challenges that bioethics faces in articulating a solid basis for LGBT rights. Timothy F. Murphy asks whether bioethics still faces issues related to lesbian, gay, and bisexual people, given the deletion of homosexuality as a disease and the progress toward same‐sex marriage. Jamie Lindemann Nelson's essay addresses the search for identity for transgender persons and the role of science in that search. Two articles, those by Brendan S. Abel and by Jack Drescher and Jack Pula, take up the complex issue of medical treatment for children who reject their assigned birth gender. Celia B. Fisher and Brian Mustanski address the special challenges of engaging LGBT youth in research, balancing the need for better information about this vulnerable group against the existing restrictions on research involving children. Tia Powell and Edward Stein consider the merits of legal bans on psychotherapies intended to change sexual orientation, particularly in the light of current research on orientation. Mary Beth Foglia and Karen I. Fredricksen‐Goldsen highlight health disparities and resilience among LGBT older adults and then discuss the role of nonconscious bias in perpetuating disparities. Stephan Davis and Nancy Berlinger assess the challenges of access to care and health policy for transgender persons. Edward J. Callahan et al. tackle the ways in which diverse aspects of medicine should change to better incorporate the needs of LGBT patients, including through use of the electronic medical record, education of health professionals, and recruitment efforts for LGBT health professionals. Virginia Ashby Sharpe and Uchenna S. Uchendu describe multifaceted efforts within Veterans Administration facilities to create change for LGBT veterans across the largest integrated health care network in the United States. Lance Wahlert and Autumn Fiester find a mixed record in the use of case studies in teaching about LGBT issues. (shrink)

In 2008, the late Allan B. Wolter, OFM worked with Oleg V. Bychkov, Ph.D. to publish a ‘safe’ version of the Reportatio IA of Franciscan Master John Duns Scotus. The publication of this first book of Scotus’s Commentary on the Sentences from his Paris teaching offered scholars an opportunity to follow the Subtle Doctor’s reasoning throughout his entire teaching career: from the earliest Lectura texts, through the Ordinatio teaching, to what many consider his final say on certain matters when he (...) taught in Paris, between 1302 and 1304.While the Ordinatio claims to have been re-worked by Scotus himself, and Reportatio IA to have been ‘examined’ by Scotus, similar claims to definitive status do not appear... (shrink)

This article reflects on the implications of the concept of health and the questions it poses for moral philosophy, psychology, and the panoply of professions that are involved in the practices of care and in the ethics of individual rights, dignity, and autonomy. Significant among these questions is what we call “the predicament of agency.” The predicament involves the ethical tensions—arising within the broad concept of health and flourishing, but also in concrete everyday practices and relationships—between supporting individual health outcomes (...) and supporting health and flourishing through respect for autonomy and self-direction. Three ways of addressing the predicament of agency are discussed: by reinterpreting the nature and requirements of autonomy (a) by appeal to reason, (b) by designing or curating contextual conditions influencing choice (often called “choice architecture” or “nudging”) in ways that constrain autonomy but do not violate its core value, and (c) by appeal to relational judgment and reflective professional practice. The article argues that each of these lines of thought is important, but none is a panacea, and none is free from conceptual confusions and ethical pitfalls of its own. The relational approach is the most promising in pointing beyond the predicament of agency—not so much by resolving it as by showing how it can be worked through without either turning our back on caring or turning caring into management and manipulation. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (shrink)

Elementary education students enrolled in both science methods and social studies methods coursework implemented standards-based STS lessons during their clinical experience. Data were collected from preservice teachers, elementary/middle school students, and cooperating in-service teachers. Findings from each school group include (a) preservice teachers' content knowledge in science and social studies hindered their development of meaningful STS curriculum, (b) the STS curriculum development and implementation experience increased preservice teachers' anxieties, (c) interviews with elementary students after the STS learning suggest that they (...) did achieve some understanding of science and social studies, and (d) cooperating in-service teachers' conceptualization of curriculum differed from the science and social studies professors' understanding. (shrink)

The rapidly increasing number of cases of Zika virus and limited understanding of its congenital sequelae (e.g., microcephaly) led to stories of fear and uncertainty across social media and other mass communication networks. In this study, we used techniques generic to netnography, a form of ethnography, using Internet‐based computer‐mediated communications as a source of data to understand the experience and perceptions of families with infants diagnosed with Zika‐related microcephaly. We screened 27 YouTube™ videos published online between October 2015 and July (...) 2016, during which the Zika epidemic started, peaked, and declined. We identified three themes: (a) experiencing the news of a diagnosis of Zika‐associated microcephaly; (b) experiencing feelings and expectations of the ‘imperfect’ child; and (c) seeking to understand microcephaly to care for the child. We found that families experienced distressing feelings of shock, sadness, hopelessness, and pain, while dealing with emerging and sometimes conflicting information being transmitted by news outlets, uncertainty about the child's health, and healthcare providers’ lack of clarity to guide the family members. The ‘unknown’ factor of ZIKA was an additional stressful factor in the experience of the families. (shrink)

In this article I give an overview of some recent work in philosophy of science dedicated to analysing the scientific process in terms of (conceptual) mathematical models of theories and the various semantic relations between such models, scientific theories, and aspects of reality. In current philosophy of science, the most interesting questions centre around the ways in which writers distinguish between theories and the mathematical structures that interpret them and in which they are true, i.e. between scientific theories as linguistic (...) systems and their non-linguistic models. In philosophy of science literature there are two main approaches to the structure of scientific theories, the statement or syntactic approach -- advocated by Carnap, Hempel and Nagel -- and the non- statement or semantic approach --advocated, among others, by Suppes, the structuralists, Beth, Van Fraassen, Giere, Wojcicki. In conclusion, I briefly review some of the usual realist inspired questions about the possibility and character of relations between scientific theories and reality as implied by the various approaches I discuss in the course of the article. The models of a scientific theory should indeed be adequate to the phenomena, but if the theory is 'adequate' to (true in) its conceptual (mathematical) models as well, we have a model-theoretic realism that addresses the possible meaning and reference of 'theoretical entities' without relapsing into the metaphysics typical of the usual scientific realist approaches. (shrink)

A collection of addresses given by men of various backgrounds at the First Institute of Ethics arranged by Beth Tzedec Congregation, Toronto.—D. J. B.

We prove that if ℵα is uncountable and regular, then the Beth-closure of Lωω(Qα) is not a sublogic of L∞ω(Qn), where Qn is the class of all n-ary generalized quantifiers. In particular, B(Lωω(Qα)) is not a sublogic of any finitely generated logic; i.e., there does not exist a finite set Q of Lindstrom quantifiers such that B(Lωω(Qα)) ≤ Lωω(Q).