The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands such (...) as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

This research investigates 3- and 5-year-olds' relative fairness in distributing small collections of even or odd numbers of more or less desirable candies, either with an adult experimenter or between two dolls. The authors compare more than 200 children from around the world, growing up in seven highly contrasted cultural and economic contexts, from rich and poor urban areas, to small-scale traditional and rural communities. Across cultures, young children tend to optimize their own gain, not showing many signs of self-sacrifice (...) or generosity. Already by 3 years of age, self-optimizing in distributive justice is based on perspective taking and rudiments of mind reading. By 5 years, overall, children tend to show more fairness in sharing. What varies across cultures is the magnitude of young children's self-interest. More fairness (less self-interest) in distributive justice is evident by children growing up in small-scale urban and traditional societies thought to promote more collective values. (shrink)

This article reports a study exploring the meaning of the complex phenomenon of moral responsibility in nursing practice. Each of three focus groups with a total of 14 student nurses were conducted twice to gather their views on moral responsibility in nursing practice. The data were analysed by qualitative thematic content analysis. Moral responsibility was interpreted as a relational way of being, which involved guidance by one’s inner compass composed of ideals, values and knowledge that translate into a striving to (...) do good. It was concluded that, if student nurses are to continue striving to do good in a way that respects themselves and other people, it is important that they do not feel forced to compromise their values. Instead they should be given space and encouragement in their endeavours to do good in a relational way that advances nursing as a moral practice. (shrink)

Advocates for the professionalization of clinical bioethics argue that bioethics professionals play an important role in contemporary medicine and patient care, especially when addressing complex ethical questions that arise in the delivery of reproductive medicine. For bioethics consultants to serve effectively, they need adequate training in the medical and ethical issues that patients and clinicians will face, and they need skills to facilitate effective dialog among all parties. Because clinical ethics consultation is a “high‐stakes endeavor” that can acutely affect patient (...) care, efforts are under way to ensure that bioethics consultants have the competence to provide such guidance. Yet to date, no studies have examined whether the training of bioethics consultants meets the needs of health care professionals who are on the front lines of such issues. In fact, limited information is available on the reproductive health issues that bioethics training programs address or the degree to which these programs meet the needs of patients confronting reproductive health decisions and their clinicians. It is therefore important to answer this key question: What are the primary ethical issues encountered in reproductive medicine that currently affect patient care? Equally important, are bioethics training programs prepared to address those issues?To begin to answer these questions, we conducted parallel surveys of directors of graduate bioethics training programs and obstetrician‐gynecologists. The goal of this project is to lay the groundwork to establish a working partnership between bioethics educators and reproductive medicine practitioners to address the often troubling and frequently complex ethical issues in reproductive medicine. (shrink)

Objectives To characterize the prevalence and content of pediatric triage policies.Methods We surveyed and solicited policies from U.S. hospitals with pediatric intensive care units. Policies were analyzed using qualitative methods and coded by 2 investigators.Results Thirty-four of 120 institutions (28%) responded. Twenty-five (74%) were freestanding children’s hospitals and 9 (26%) were hospitals within a hospital. Nine (26%) had approved policies, 9 (26%) had draft policies, 5 (14%) were developing policies, and 7 (20%) did not have policies. Nineteen (68%) institutions shared (...) their approved or draft policy. Eight (42%) of those policies included neonates. The polices identified 0 to 5 (median 2) factors to prioritize patients. The most common factors were short- (17, 90%) and long- (14, 74%) term predicted mortality. Pediatric scoring systems included Pediatric Logistic Organ Dysfunction-2 (12, 63%) and Score for Neonatal Acute Physiology and Perinatal Extensions-II (4, 21%). Thirteen (68%) policies described a formal algorithm. The most common tiebreakers were random/lottery (10, 71%) and life cycles (9, 64%). The majority (15, 79%) of policies specified the roles of triage team members and 13 (68%) precluded those participating in patient care from making triage decisions.Conclusions While many institutions still do not have pediatric triage policies, there appears to be a trend among those with policies to utilize a formal algorithm that focuses on short- and long-term predicted mortality and that incorporates age-appropriate scoring systems. Additional work is needed to expand access to pediatric-specific policies, to validate scoring systems, and to address health disparities. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

This paper presents the first bibliometric mapping analysis of the field of computer and information ethics (C&IE). It provides a map of the relations between 400 key terms in the field. This term map can be used to get an overview of concepts and topics in the field and to identify relations between information and communication technology concepts on the one hand and ethical concepts on the other hand. To produce the term map, a data set of over thousand articles (...) published in leading journals and conference proceedings in the C&IE field was constructed. With the help of various computer algorithms, key terms were identified in the titles and abstracts of the articles and co-occurrence frequencies of these key terms were calculated. Based on the co-occurrence frequencies, the term map was constructed. This was done using a computer program called VOSviewer. The term map provides a visual representation of the C&IE field and, more specifically, of the organization of the field around three main concepts, namely privacy, ethics, and the Internet. (shrink)

PurposeThe purpose of this study is to describe the implementation and outcomes of an Eye Movement and Desensitization Reprocessing treatment-program for women with posttraumatic stress disorder after childbirth.MethodsA prospective cohort-study with pre- and post-measurements was carried out in the setting of an academic hospital in the Netherland. Included were women who gave birth to a living child at least 4 weeks ago, with a diagnosis of PTSD, or severe symptoms of PTSD combined with another psychiatric diagnosis. All received up to (...) 8 sessions of EMDR-therapy. The posttraumatic stress disorder Checklist for DSM-5 was administered before and after treatment. Trauma history was assessed before treatment with the Life Events Checklist for the DSM-5, the Childhood Trauma Questionnaire and the Childbirth Perception Scale. Descriptive statistics were used.ResultsForty-four women were referred, 26 met the inclusion criteria. After treatment, none of the women met the criteria for diagnosis of PTSD after on average 5 weekly sessions of EMDR- therapy. These outcomes are promising, as they were achieved in women with relatively high levels of psychiatric comorbidity and high rates of previous mental health treatment.ConclusionImplementing an EMDR-treatment program for women with PTSD after childbirth in the setting of an academic hospital is feasible and effective. Key factors for success include a close collaboration between the relevant hospital departments and a thorough case conceptualization addressing the etiology of the PTSD. (shrink)

The step to e-research in philosophy depends on the availability of high quality, easily and freely accessible corpora in a sustainable format composed from multi-language, multi-script books from different historical periods. Corpora matching these needs are at the moment virtually non-existing. Within @PhilosTei, we have addressed this corpus building problem by developing an open source, web-based, user-friendly workflow from textual images to TEI, based on state-of-the-art open source OCR software, to wit Tesseract, and a multi-language version of TICCL, a powerful (...) OCR post-correction tool. We have demonstrated the utility of the tool by applying it to a multilingual, multi-script corpus of important eighteenth to twentieth-century European philosophical texts. (shrink)

A shift towards more environmentally friendly and socially responsible food systems is a key step in the achievement of global sustainable development goals. To obtain significant results, however, it is essential to find participative ways to frame food sustainability objectives, so they can speak to a wide array of actors of change. This article addresses the promising potential of empowering actors across the food system to make a shift in their food choices, by facilitating the association of food sustainability values (...) with contemporary moral issues. In this context, a conceptual framework for a transition towards food sustainability is proposed, based upon the concept of the moral circle. This approach transcends the human-centred methods enacted in traditional sustainable development agendas, offering an alternative with a more holistic perspective. It is expected that emphasising moral reflection around sustainability might encourage societal participation in the creation of sustainable, fair and healthier food systems. (shrink)

A shift towards more environmentally friendly and socially responsible food systems is a key step in the achievement of global sustainable development goals. To obtain significant results, however, it is essential to find participative ways to frame food sustainability objectives, so they can speak to a wide array of actors of change. This article addresses the promising potential of empowering actors across the food system to make a shift in their food choices, by facilitating the association of food sustainability values (...) with contemporary moral issues. In this context, a conceptual framework for a transition towards food sustainability is proposed, based upon the concept of the moral circle. This approach transcends the human-centred methods enacted in traditional sustainable development agendas, offering an alternative with a more holistic perspective. It is expected that emphasising moral reflection around sustainability might encourage societal participation in the creation of sustainable, fair and healthier food systems. (shrink)

This volume addresses the intriguing issue of indirect reports from an interdisciplinary perspective. The contributors include philosophers, theoretical linguists, socio-pragmaticians, and cognitive scientists. The book is divided into four sections following the provenance of the authors. Combining the voices from leading and emerging authors in the field, it offers a detailed picture of indirect reports in the world’s languages and their significance for theoretical linguistics. Building on the previous book on indirect reports in this series, this volume adds an empirical (...) and cross-linguistic approach that covers an impressive range of languages, such as Cantonese, Japanese, Hebrew, Persian, Dutch, Spanish, Catalan, Armenian, Italian, English, Hungarian, German, Rumanian, and Basque. (shrink)

We argue that an adequate treatment of verb phrase anaphora must depart in two major respects from the standard approaches. First of all, VP anaphors cannot be resolved by simply identifying the anaphoric VP with an antecedent VP. The resolution process must establish a syntactic/semantic parallelism between larger units that the VPs occur in. Secondly, discourse structure has a significant influence on the reference possibilities of VPA. This influence must be accounted for. We propose a treatment which meets these requirements. (...) It builds on a discourse grammar which characterizes discourse cohesion by means of a syntactic/semantic matching procedure which recognizes parallel structures in discourse. It turns out that this independently motivated procedure yields the resolution of VPA as a side effect. (shrink)

In our daily lives, we continuously evaluate feedback information, update our knowledge, and adapt our behavior in order to reach desired goals. This ability to learn from feedback information, however, declines with age. Previous research has indicated that certain higher-level learning processes, such as feedback evaluation, integration of feedback information, and updating of knowledge, seem to be affected by age, and recent studies have shown how the adaption of choice behavior following feedback can differ with age. The neural mechanisms underlying (...) this age-related change in choice behavior during learning, however, remain unclear. The aim of this study is therefore to investigate the relation between learning-related neural processes and choice behavior during feedback learning in two age groups. Behavioral and fMRI data were collected, while a group of young and older adults performed a probabilistic learning task consisting of 10 blocks of 20 trials each. On each trial, the participants chose between a house and a face, after which they received visual feedback. In each block, either the house or the face image had a higher probability of yielding a reward. Participants were instructed to try to maximize their gains. Our results showed that less successful learning in older adults, as indicated by a lower learning rate, corresponded with a higher tendency to switch to the other stimulus option, and with a reduced adaptation of this switch choice behavior following positive feedback. At the neural level, activation following positive and negative feedback was found to be less distinctive in the older adults, due to a smaller feedback-evaluation response to positive feedback in this group. Furthermore, whereas young adults displayed increased levels of knowledge updating prior to adapting choice behavior, we did not find this effect in older adults. Together, our results suggest that diminished learning performance with age corresponds with diminished evaluation of positive feedback and reduced knowledge updating related to changes in choice behavior, indicating how such differences in feedback processing at the trial level in older adults might lead to reduced learning performance across trials. (shrink)

This study bases itself in the epistemological and methodological development of a broad and interdisciplinary dialogue where various voices in the form of different domains converse in order to establish an integrated whole. The research contributes to the actual corporative question regarding spirituality in the workplace, specifically aimed at the individual in the middle-career phase. This phase is characterised as a re-evaluation period aimed at personal and professional growth. A shift in emphasis to the meaning and sense of work is (...) linked to spiritual intelligence as spirituality can be described and understood as a type of intelligence. The study shows that the middle-career experience provides opportunity for an altered future view. Lifestyle coaching serves as facilitating process and offers guidance in answering existential questions which are included in the spiritual. The probable outcome promises to add meaning as a manifesting component in a dynamic and transforming life strategy. (shrink)

This paper presents the first bibliometric mapping analysis of the field of computer and information ethics (C&IE). It provides a map of the relations between 400 key terms in the field. This term map can be used to get an overview of concepts and topics in the field and to identify relations between information and communication technology concepts on the one hand and ethical concepts on the other hand. To produce the term map, a data set of over thousand articles (...) published in leading journals and conference proceedings in the C&IE field was constructed. With the help of various computer algorithms, key terms were identified in the titles and abstracts of the articles and co-occurrence frequencies of these key terms were calculated. Based on the co-occurrence frequencies, the term map was constructed. This was done using a computer program called VOSviewer. The term map provides a visual representation of the C&IE field and, more specifically, of the organization of the field around three main concepts, namely privacy, ethics, and the Internet. (shrink)

Libraries provide access to large amounts of library metadata. Unfortunately, many libraries only offer textual interfaces for searching and browsing their holdings. Visualizations provide simpler, faster, and more efficient ways to navigate, search and study large quantities of metadata. This paper presents GlamMap, a visualization tool that displays library metadata on an interactive, computer-generated geographic map. We provide detailed discussion of how GlamMap benefits the work of librarians and researchers. We show how geographic representations help librarians to perform tasks such (...) as collection assessment and how geographic information helps researchers to identify important scientific resources. (shrink)

This paper presents the current state of development of GlamMap, a visualisation tool that displays library metadata on an interactive, computer-generated geographic map. The focus in the paper is on the most crucial improvement achieved in the development of the tool: GlamMapping Trove. The visualisation of Trove’s sixtymillion book records is possible thanks to an improved database structure, more efficient data retrieval, and more scalable visualisation algorithms. The paper analyses problems encountered in visualising massive datasets, describes remaining challenges for the (...) tool, and presents a use case demonstrating GlamMap’s ability to serve researchers in the history of ideas. (shrink)

Features essays on moral philosophy written in honor of Elizabeth Flower's retirement.

The South African government’s COVID-19 pandemic risk mitigation strategies significantly limited social contact, which necessitated a novel approach to existing face-to-face career guidance practices. The Grade 9 Career Guidance Project, originally developed as a group-based career development intervention, required radical adaptation into a self-directed, manualized format to offer career guidance to Grade 9 learners from low-income communities amid a global pandemic. The adaptation and continuation of the project was deemed essential as secondary school learners in low-income communities have limited career (...) guidance support. Furthermore, a close collaboration with the teachers at eight resource-constrained South African secondary schools was vital for successful implementation. To assess the success of the adaptation to a self-directed format, a mixed-methods design was employed, and Life Orientation teachers’ evaluative feedback was solicited. Favorable quantitative results were obtained; majority of teachers agreed that learners enjoyed the booklet and that it was deemed an adequate substitute to the previous contact-based format of the Career Guidance Project. This was also confirmed by the qualitative findings revealing teachers’ satisfaction with the booklet’s content, specifically that the booklet is complementary to the Life Orientation curriculum. Qualitative findings identified specific contextual barriers that contributed to some learners struggling to use the booklet optimally. The results suggest that it is feasible and acceptable to implement a self-directed career guidance intervention among secondary school learners amid a global pandemic. Teachers recommended ways to integrate the booklet, resources, and contact sessions as a preferred way forward. These findings have important implications for similar resource-constrained settings that may not have readily access to in-person career guidance and counseling human development. (shrink)

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a (...) criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable. (shrink)

BackgroundAntipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment.MethodsWe conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined metabolic groups.ResultsTwelve (...) studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers, 633 intermediate metabolizers, 1,272 normal metabolizers, and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were PM versus NM; weight = –0.07, BMI = 0.40. IM versus NM; weight = 0.09 and BMI = 0.09. UM versus EM; weight = 0.01 and BMI = –0.08.ConclusionOur systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health. (shrink)