Transcriptional silencing may not necessarily depend on the continuous residence of a sequence‐specific repressor at a control element and may act via a “hit and run” mechanism. Due to limitations in assays that detect transcription factor (TF) binding, such as chromatin immunoprecipitation followed by high‐throughput sequencing (ChIP‐seq), this phenomenon may be challenging to detect and therefore its prevalence may be underappreciated. To explore this possibility, erythroid gene promoters that are regulated directly by GATA1 in an inducible system are analyzed. It (...) is found that many regulated genes are bound immediately after induction of GATA1 but the residency of GATA1 decreases over time, particularly at repressed genes. Furthermore, it is shown that the repressive mark H3K27me3 is seldom associated with bound repressors, whereas, in contrast, the active (H3K4me3) histone mark is overwhelmingly associated with TF binding. It is hypothesized that during cellular differentiation and development, certain genes are silenced by repressive TFs that subsequently vacate the region. Catching such repressor TFs in the act of silencing via assays such as ChIP‐seq is thus a temporally challenging prospect. The use of inducible systems, epitope tags, and alternative techniques may provide opportunities for detecting elusive “hit and run” transcriptional silencing. Also see the video abstract here https://youtu.be/vgrsoP_HF3g. (shrink)

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala (...) and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. (shrink)

Hospital ethics committees have become widespread over the last 25 years, stimulated by the Quinlan decision of the New Jersey Supreme Court, the report of a President's Commission, and most recently by the Joint Commission on Accreditation of Health Care Organizations , which now man dates that each hospital seeking accreditation have a functioning process for the consideration of ethical issues in patient care. Laws and regulations in several states require that hospitals establish ethics committees, and some states stipulate (...) that certain types of cases and disputes be taken to such committees. At least one state grants legal immunity to those who implement recommendations of an ethics committee. (shrink)

Hospital ethics committees have become widespread over the last 25 years, stimulated by the Quinlan decision of the New Jersey Supreme Court, the report of a President's Commission, and most recently by the Joint Commission on Accreditation of Health Care Organizations, which now man dates that each hospital seeking accreditation have a functioning process for the consideration of ethical issues in patient care. Laws and regulations in several states require that hospitals establish ethics committees, and some states stipulate that (...) certain types of cases and disputes be taken to such committees. At least one state grants legal immunity to those who implement recommendations of an ethics committee. (shrink)

Over the past two decades ethics committees have proliferated in healthcare institutions across the country. Catalysts for this growth include the endorsement of ethics committees by the New Jersey Supreme Court in the Quinlan case, by the President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research in its report entitled Deciding to Forgo Life Sustaining Medical Treatment, by the U.S. Department of Health and Human Services in its 1985 “Baby Doe” regulations, by numerous other courts (...) in treatment decisionmaking opinions issued after Quinlan, and more recently by the Joint Commission on Accreditation of Healthcare Organizations. (shrink)

IntroductionExtended decision -making through the use of proxy decision -makers has been enshrined in a range of International Codes, Professional Guidance and Statute,For example, the UK Mental Capacity Act section 9.1; The General Medical Council ; the US National Guardianship Association ; Nuffield Council on Bioethics ; CIOMS-WHO section 6. Court cases such as Re Quinlan in the US have also contributed to establishing the groundings for the legal status of the proxy, albeit in terms of who might be (...) suitable as a proxy in cases where there was no clear appointment of them by a still competent individual. and is now widely seen as a useful means through which we can exercise control over decisions that affect our lives when we have lost capacity to make these decisions for ourselves.I will here limit myself to discussion of proxy consent for adults appointed prior to the loss of competence by the person they are acting as proxy for. The issue of p. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Ethics Committees in HospitalsPat Milmoe McCarrick (bio)(Literature about hospital ethics committees has grown enormously since Scope Note 3 first appeared. This update provides new information about resources and documents now available while continuing to include important earlier sources.)Hospital ethics committees increasingly have taken hold in the United States since 1983, when the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research encouraged their (...) creation in its report, Deciding to Forego Life-Sustaining Treatment (III, 1983, p. 5).The President's Commission report (pp. 160-64) suggested the following roles for ethics committees: 1) review of treatment decisions made on behalf of incompetent, terminally ill patients; 2) review of medical decisions having ethical implications with the option, in cases of disagreement, to refer cases to a court with proper jurisdiction; 3) provision of social, psychological, spiritual, or other counseling for patients, family members, physicians, or other hospital staff; 4) establishing guidelines regarding treatment or other medical decisions; and 5) sponsoring or conducting educational programs to inform all concerned, including the public, about ethical problems in medicine.No exact count of these committees is available. According to estimates cited by Donald F. Phillips, managing editor of Hospital Ethics, about two-thirds to three-fourths of hospitals with more than 200 beds have ethics committees, as do about one-third of hospitals under 200 beds. He thinks that about half of the 6,000 hospitals in the United States now have working ethics committees.Several journal articles and a court decision in the late 1970s influenced their formation. A 1975 journal article by pediatrician Karen Teel (VII A) urged the use of hospital ethics committees to provide for dialogue in individual care situations as an appropriate sharing of responsibility. Another early article suggested that beyond parents and treating physicians, a "disinterested," mixed lay and medical committee could consider cases about defective newborns to improve the ethical decisionmaking process (VII A, Robertson and Fost, 1976). Three 1977 discussions in the Hastings Center Report highlighted this new concept (VII A, Levine; Shannon; Veatch).Produced at the National Reference Center for Bioethics Literature, Kennedy Institute of Ethics, Georgetown University, Washington, DC 20057. It is supported by funds provided under grant number LM04492 from the National Library of Medicine, National Institutes of Health. Literature available through June 1992 is represented in this Scope Note. [End Page 285]The court decision was the March 31, 1976 ruling by the New Jersey Supreme Court in the Karen Quinlan case. The parents of a young woman in a persistent vegetative state had requested that she be taken off a respirator. The court designated a "prognosis" role for the hospital ethics committee and stipulated that the committee must concur that the patient will never return to a "cognitive, sapient state" before the life-support system can be withdrawn (In the Matter of Karen Quinlan, 70 N.J. 10, 355 A.2d 647, cert. denied sub nom. Garger v. New Jersey, 429 U.S. 922 (1976)). Shortly after the Quinlan decision, Massachusetts General Hospital's Clinical Care Committee created an ad hoc subcommittee (a psychiatrist, a legal counsel, an ICU nurse, an oncologist/internist, a surgeon, and a lay person who had recovered from serious cancer disease) which looked at 15 cases. Based on the subcommittee's success, establishment of a permanent committee to review treatment of the terminally ill was recommended by the critical care committee (VII A, Clinical Care Committee 1976).In its 1984 Baby Doe rules, the federal government recommended establishment of infant care review committees, which promoted the growth of hospital ethics committees (VII C, Povar 1991). In July 1987 Maryland became the first state to require by law that hospitals establish patient care advisory committees to offer advice about choices available in the care of life-threatening illnesses; this requirement was extended to nursing homes in 1990 [codified as amended at Md. Health-Gen. Code Ann. Sections 19-370 to -374 (1990)] (VII C, Hollinger 1991).Recently the role for these committees has been noted in the Accreditation Manual for Hospitals, 1992 Supplement (p. 10, Patient Rights, Section RI. 1.1.6.1) of the Joint Commission... (shrink)

The article criticises the attempt to establish connectionism as an alternative theory of human cognitive architecture through the introduction of thesymbolic/subsymbolic distinction (Smolensky, 1988). The reasons for the introduction of this distinction are discussed and found to be unconvincing. It is shown that thebrittleness problem has been solved for a large class ofsymbolic learning systems, e.g. the class oftop-down induction of decision-trees (TDIDT) learning systems. Also, the process of articulating expert knowledge in rules seems quite practical for many important domains, (...) including common sense knowledge.The article discusses several experimental comparisons betweenTDIDT systems and artificial neural networks using the error backpropagation algorithm (ANNs usingBP). The properties of one of theTDIDT systemsID3 (Quinlan, 1986a) are examined in detail. It is argued that the differences in performance betweenANNs usingBP andTDIDT systems reflect slightly different inductive biases but are not systematic; these differences do not support the view that symbolic and subsymbolic systems are fundamentally incompatible. It is concluded, that thesymbolic/subsymbolic distinction is spurious. It cannot establish connectionism as an alternative cognitive architecture. (shrink)

This collection of eight articles of uneven quality examines ethical and moral considerations surrounding "euthanasia." They all concentrate more on philosophic issues such as decision-making, principles and theories of action and accountability, and definitions than on medical dilemmas which bring such questions to prominence. Except for Ladd’s they seem unfamiliar with current law on the issues, and most, we suspect, took shape before Saikewicz, if not before the appellate decision on Quinlan. There are four principal themes. The alleged distinction, (...) rejected by all but P. Foot, between active and passive euthanasia. The nature and origin of certain concepts such as "right", "death," and "person." The problem of whether rights can be located elsewhere than in persons. Special problems such as Down’s Syndrome infants and infanticide in general. (shrink)

A continuoxis t- norm is a continuous map * from [0, 1]² into [0,1] such that is a commutative totally ordered monoid. Since the natural ordering on [0,1] is a complete lattice ordering, each continuous t-norm induces naturally a residuation → and becomes a commutative naturally ordered residuated monoid, also called a hoop. The variety of basic hoops is precisely the variety generated by all algebras, where * is a continuous t-norm. In this paper we investigate the structure of the (...) variety of basic hoops and some of its subvarieties. In particular we provide a complete description of the finite subdirectly irreducible basic hoops, and we show that the variety of basic hoops is generated as a quasivariety by its finite algebras. We extend these results to Hájek's BL-algebras, and we give an alternative proof of the fact that the variety of BL-algebras is generated by all algebras arising from continuous t-norms on [ 0,1] and their residua. The last part of the paper is devoted to the investigation of the subreducts of BL- algebras, of Gödel algebras and of product algebras. (shrink)

A continuoxis t- norm is a continuous map * from [0, 1]² into [0,1] such that ([ 0,1], *, 1) is a commutative totally ordered monoid. Since the natural ordering on [0,1] is a complete lattice ordering, each continuous t-norm induces naturally a residuation → and ([ 0,1], *, →, 1) becomes a commutative naturally ordered residuated monoid, also called a hoop. The variety of basic hoops is precisely the variety generated by all algebras ([ 0,1], *, →, 1), where (...) * is a continuous t-norm. In this paper we investigate the structure of the variety of basic hoops and some of its subvarieties. In particular we provide a complete description of the finite subdirectly irreducible basic hoops, and we show that the variety of basic hoops is generated as a quasivariety by its finite algebras. We extend these results to Hájek's BL-algebras, and we give an alternative proof of the fact that the variety of BL-algebras is generated by all algebras arising from continuous t-norms on [ 0,1] and their residua. The last part of the paper is devoted to the investigation of the subreducts of BL- algebras, of Gödel algebras and of product algebras. (shrink)

We develop and apply a multi-dimensional conception of explanatory depth towards a comparative analysis of inflationary and bouncing paradigms in primordial cosmology. Our analysis builds on earlier work due to Azhar and Loeb (2021) that establishes initial condition fine-tuning as a dimension of explanatory depth relevant to debates in contemporary cosmology. We propose dynamical fine-tuning and autonomy as two further dimensions of depth in the context of problems with instability and trans-Planckian modes that afflict bouncing and inflationary approaches respectively. In (...) the context of the latter issue, we argue that the recently formulated trans-Planckian censorship conjecture leads to a trade-off for inflationary models between dynamical fine-tuning and autonomy. We conclude with the suggestion that explanatory preference with regard to the different dimensions of depth is best understood in terms of differing attitudes towards heuristics for future model building. (shrink)

Distributive, procedural, and interactional justice are constructs that are increasingly being recognized as important factors that affect individual perceptions in the workplace environment. This paper presents a theoretical perspective that suggests that justice is perceived through a subjective lens that consists of individualized beliefs and proposes that cultural attributes and demographic characteristics play an integral part in determining the perception of justice. The distinctions between these three constructs are presented in context with the core beliefs of individual employees – affected (...) by a multitude of perceptual and demographic factors that we briefly identify herein. Based on the theoretical perspective, an instrument that measures the constructs of justice as perceived by individuals was developed. With a focus on justice within the business setting, hypotheses about attitudes related to justice were tested. Survey results confirm that the three constructs of justice are distinct but correlated. Significant differences were found in the perceptions of African-American respondents with regard to procedural justice. Although the empirical findings do not support all the hypotheses, this research highlights the need for further development of measures to assess the perception of justice in business settings and at an applied level, underscores the importance of recognizing cultural attributes and demographic characteristics in understanding how justice is perceived. (shrink)

When I offered this title, I was engaging myself to investigate an apparent difference between two kinds of intentionality, in the hope that I should be able to find some firm logical criterion to distinguish them. I was less successful in this than I had hoped. I think I have gained a certain amount of insight into the logic and semantics of one kind of intentional context, largely due to the work I was doing while visiting the University of Pennsylvania (...) on Frege and on Michael Dummett’s monumental commentary on Frege. But as regards the other variety of intentionality I am still very much in the dark; so I am giving you thus far merely a progress report on that. (shrink)

D. Z. Phillips is a leading figure in advocating a Wittgensteinian approach to the philosophical study of religion. His writings exert an important influence on contemporary philosophy of religion, giving a new direction to the philosophical discussion of religious belief and practice. Although his work has prompted much - often critical - comment, a thorough investigation has not been forthcoming. Grammars of Faith fills that gap. The book pays close attention to Wittgenstein's own remarks on religious belief, arranging them against (...) the background of his broader philosophical methodology, as well as to the efforts of the early Wittgensteinians at providing a more comprehensive Wittgensteinian philosophy of religion. Central to this study are Phillips's understanding of philosophical enquiry as a form of contemplation, and his descriptive accounts of religious belief. By means of a careful and methodical examination of Phillips's oeuvre, the study seeks to present a fair assessment of Phillips's position, showing not only its weaknesses, but also its strength. (shrink)

P S Wilson; Child-Centred Education, Journal of Philosophy of Education, Volume 3, Issue 1, 30 May 2006, Pages 105–126, https://doi.org/10.1111/j.1467-9752.1969.

In this essay, P. Taylor Webb and Kalervo N. Gulson argue that educational policy is a spatial process and that implementation processes in particular produce crucial emergent geographies for policy research. Webb and Gulson describe how emergent geographies are produced when policy folds actors through senses and enactments of policy. The idea that policy is sensed and enacted is developed into the concept of a policy intension that extends approaches to spatial and, in particular, micropolitical analyses in policy research. Webb (...) and Gulson conclude by discussing cartographical methods that better map the geographies of subjectivity produced through policy intensions. (shrink)

P S Wilson; Perspectives on Punishment—Reply to Pamela Moore, Journal of Philosophy of Education, Volume 8, Issue 1, 30 May 2006, Pages 103–134, https://doi.org.