Apoptosis is now widely recognized as a common form of cell death and represents a mechanism of cell clearance in many physiological situations where deletion of cells is required. Peptide growth factors, initially characterised as stimulators of cell proliferation, have now been shown to inhibit death in many cell types. Deprivation of growth factors leads to the induction of apoptosis, i.e. condensation of chromatin and degradation in oligonucleosomesized fragments, formation of plasma and nuclear membrane blebs and cell fragmentation into apoptotic (...) bodies which can be taken up by neighbouring cells. Here we discuss the mechanism(;s) by which growth factors may inhibit apoptosis. (shrink)

More than 200 million children under the age of 5 years are affected by malnutrition worldwide according to the World Health Organization. The Barbados Nutrition Study (BNS) is a 55-year longitudinal study on a Barbadian cohort with histories of moderate to severe protein-energy malnutrition (PEM) limited to the first year of life and a healthy comparison group. Using quantitative electroencephalography (EEG), differences in brain function duringchildhood(lower alpha1 activity and higher theta, alpha2 and beta activity) have previously been highlighted between participants (...) who suffered from early PEM and controls. In order to determine whether similar differences persisted intoadulthood, our current study used recordings obtained during a Go-No-Go task in a subsample of the original BNS cohort [population size (N) = 53] at ages 45–51 years. We found that previously malnourished adults [sample size (n) = 24] had a higher rate of omission errors on the task relative to controls (n= 29). Evoked-Related Potentials (ERP) were significantly different in participants with histories of early PEM, who presented with lower N2 amplitudes. These findings are typically associated with impaired conflict monitoring and/or attention deficits and may therefore be linked to the attentional and executive function deficits that have been previously reported in this cohort in childhood and again in middle adulthood. (shrink)

The Search for the Legacy of the USPHS Syphilis Study at Tuskegee is a collection of essays from experts in a variety of fields seeking to redefine the legacy of the infamous Tuskegee Syphilis Study. The essayists place the legacy of the study within the evolution of racial and ethnic relations in the United States. Contributors include two leading historians on the study, two former United States Surgeons General, and other prominent scholars from a wide range of fields.

Do the rich descriptions and narrative shapings of literature provide a valuable resource for readers, writers, philosophers, and everyday people to imagine and confront the ultimate questions of life? Do the human activities of storytelling and complex moral decision-making have a deep connection? What are the moral responsibilities of the artist, critic, and reader? What can religious perspectives—from Catholic to Protestant to Mormon—contribute to literary criticism? Thirty well known contributors reflect on these questions, including iterary theorists Marshall Gregory, James Phelan, (...) and Wayne Booth; philosophers Martha Nussbaum, Richard Hart, and Nina Rosenstand; and authors John Updike, Charles Johnson, Flannery O'Connor, and Bernard Malamud. Divided into four sections, with introductory matter and questions for discussion, this accessible anthology represents the most crucial work today exploring the interdisciplinary connections between literature, religion and philosophy. (shrink)

Retaliation against whistleblowers is a well-recognized problem, yet there is little explanation for why uninvolved peers choose to retaliate through ostracism. We conduct two experiments in which participants take the role of a peer third-party observer of theft and subsequent whistleblowing. We manipulate injunctive norms and descriptive norms. Both experiments support the core of our theoretical model, based on social intuitionist theory, such that moral judgments of the acts of wrongdoing and whistleblowing influence the perceived likeability of each actor and (...) ultimately influence intention to ostracize each actor and indicate more willingness to ostracize the whistleblower than the wrongdoer. When we vary norms for the wrongdoing in Experiment 1, we find that descriptive and injunctive norms indirectly influence intentions to ostracize both the wrongdoer and whistleblower. These relationships are serially mediated by the observers’ moral judgments of the act and likeability of the actor. When we vary norms for whistleblowing in Experiment 2, the injunctive norm manipulation affected moral judgment of the action of whistleblowing, and we do not observe any other significant effects of the norm manipulations on moral judgments of the actions of wrongdoing or whistleblowing. (shrink)

The development and utility of genetically modified crops for smallholders around the world is controversial. Critical questions include what traits and crops are to be developed; how they can be adapted to smallholders’ ecological, social and economic contexts; which dissemination channels should be used to reach smallholders; and which policy environments will enable the greatest benefits for smallholders and the rural poor. A key question is how the voices of smallholders who have experience with or desire to use GM technologies (...) enter the larger debate. Africa has the greatest number of smallholders and poor with the least exposure to GM crops. Because of the well-established use of GM crops in South Africa by commercial farmers, we formed a community of practice involving smallholders, extension, researchers, non-profits and agribusiness in KwaZulu-Natal to examine the conditions under which GM crops are used by smallholders, how smallholders interact with GM technologies and what insights smallholders and other stakeholders can provide regarding these questions. One of the advantages of the CoP approach is that it brings stakeholders together in a non-hierarchical way that encourages new ways of thinking and new partnerships. Such interaction around a specific project can enhance the voice of smallholders in a variety of ways. In our project, smallholder participants have increased their knowledge and can make better decisions about GM technologies, which had been barriers for them. Notably, they have also improved their knowledge of maize production practices, accessed new practice networks, and met new researchers and resource providers. They are now being integrated into these networks in a way that should improve their livelihoods and make the wants and needs of smallholders better known. Such knowledge and experience has improved their voice in agriculture and rural development discussions. (shrink)

In cognitive science, there is a tacit norm that phenomena such as cultural variation or synaesthesia are worthy examples of cognitive diversity that contribute to a better understanding of cognition, but that other forms of cognitive diversity (e.g., autism, attention deficit hyperactivity disorder/ADHD, and dyslexia) are primarily interesting only as examples of deficit, dysfunction, or impairment. This status quo is dehumanizing and holds back much-needed research. In contrast, the neurodiversity paradigm argues that such experiences are not necessarily deficits but rather (...) are natural reflections of biodiversity. Here, we propose that neurodiversity is an important topic for future research in cognitive science. We discuss why cognitive science has thus far failed to engage with neurodiversity, why this gap presents both ethical and scientific challenges for the field, and, crucially, why cognitive science will produce better theories of human cognition if the field engages with neurodiversity in the same way that it values other forms of cognitive diversity. Doing so will not only empower marginalized researchers but will also present an opportunity for cognitive science to benefit from the unique contributions of neurodivergent researchers and communities. (shrink)

Pandemics first and foremost hit those who are most vulnerable, and the COVID-19 pandemic is not different. Although the infection rate in the nation’s poorest neighborhoods is twice as it is in th...

BackgroundThe emergence of artificial intelligence (AI) in medicine has prompted the development of numerous ethical guidelines, while the involvement of patients in the creation of these documents lags behind. As part of the European PROFID project we explore patient perspectives on the ethical implications of AI in care for patients at increased risk of sudden cardiac death (SCD).AimExplore perspectives of patients on the ethical use of AI, particularly in clinical decision-making regarding the implantation of an implantable cardioverter-defibrillator (ICD).MethodsSemi-structured, future scenario-based (...) interviews were conducted among patients who had either an ICD and/or a heart condition with increased risk of SCD in Germany (n = 9) and the Netherlands (n = 15). We used the principles of the European Commission’s Ethics Guidelines for Trustworthy AI to structure the interviews.ResultsSix themes arose from the interviews: the ability of AI to rectify human doctors’ limitations; the objectivity of data; whether AI can serve as second opinion; AI explainability and patient trust; the importance of the ‘human touch’; and the personalization of care. Overall, our results reveal a strong desire among patients for more personalized and patient-centered care in the context of ICD implantation. Participants in our study express significant concerns about the further loss of the ‘human touch’ in healthcare when AI is introduced in clinical settings. They believe that this aspect of care is currently inadequately recognized in clinical practice. Participants attribute to doctors the responsibility of evaluating AI recommendations for clinical relevance and aligning them with patients’ individual contexts and values, in consultation with the patient.ConclusionThe ‘human touch’ patients exclusively ascribe to human medical practitioners extends beyond sympathy and kindness, and has clinical relevance in medical decision-making. Because this cannot be replaced by AI, we suggest that normative research into the ‘right to a human doctor’ is needed. Furthermore, policies on patient-centered AI integration in clinical practice should encompass the ethics of everyday practice rather than only principle-based ethics. We suggest that an empirical ethics approach grounded in ethnographic research is exceptionally well-suited to pave the way forward. (shrink)

It is generally accepted that appropriate documentation of activities and recommendations of ethics consultants in patients’ medical records is critical. Despite this acceptance, the bioethics literature is largely devoid of guidance on key elements of an ethics chart note, the degree of specificity that it should contain, and its stylistic tenor. We aim to provide guidance for a variety of persons engaged in clinical ethics consultation: new and seasoned ethics committee members who are new to ethics consultation, students and trainees (...) in clinical ethics, and those who have significant experience with ethics consultation so that they can reflect on their practice. Toward the goal of promoting quality charting practices in ethics consultations, we propose recommendations on a broad array of questions concerning clinical ethics consultation chart notes, including whether and when to write a chart note, and practical considerations for the tenor, purpose, and content of a chart note. Our broader aim is to promote discussion about good charting practices in clinical ethics, with the hope of contributing to clear standards of excellence in clinical ethics consultation. (shrink)

While valuable work has been done addressing clinical ethics within established healthcare systems, we anticipate that the projected growth in acquisitions of community hospitals and facilities by large tertiary hospitals will impact the field of clinical ethics and the day-to-day responsibilities of clinical ethicists in ways that have yet to be explored. Toward the goal of providing clinical ethicists guidance on a range of issues that they may encounter in the systematization process, we discuss key considerations and potential challenges in (...) implementing system-wide ethics consultation services. Specifically, we identify four models for organizing, developing, and enhancing ethics consultation activities within a system created through acquisitions: train-the-trainer, local capacity-building, circuit-riding, and consolidated accountability. We note each model’s benefits and challenges. To our knowledge, this is the first paper to consider the broader landscape of issues affected by consolidation. We anticipate that clinical ethicists, volunteer consultants, and hospital administrators will benefit from our recommendations. (shrink)

The clinical ethicist met with Ms. H to clarify what information she wants and does not want to know. First, she wants to receive any treatment that could prolong her life, regardless of how the treatment affects her ability to engage in activities of daily living. Second, she wants to be included in the decision‐making process as much as possible, as long as clinicians use only “positive” language. Ms. H considers the words “dying,” “chemotherapy,” “radiation,” and “cancer” to be “bad (...) words.” For conversations in which these words cannot be avoided, she wants her clinicians to talk to her son. Her desired engagement includes hearing about risks, benefits, and alternatives to treatments if clinicians use only “positive” language. Finally, she says that she rarely sees doctors and that she is “very scared” of hospitals, despite exhibiting a comfortable demeanor.Should clinicians honor Ms. H's waiver of specified information and, if so, to what degree? (shrink)

In our target article (Sabatello et al. 2021), we proposed the use of community engagement and the establishment of a Truth and Reconciliation Commission (TRC) as pathways for promoting social just...

The existence of free will has been both an enduring presumption of Western culture and a subject for debate across disciplines for millennia. However, little empirical evidence exists to support the almost unquestioned assumption that, in general, Westerners endorse the existence of free will. The few studies that measure belief in free will have methodological problems that likely resulted in underestimating the true extent of belief. Recently, Rakos et al. (Behavior and Social Issues 17:20–39, 2008 ) found a stronger endorsement (...) of free will when demand characteristics were eliminated. The current study builds on this work by sampling incarcerated adolescents and adults, whose freedom to act is externally constrained. Belief in free will as well as attitudes toward punishment, self-esteem, and locus of control were measured. The results indicate that free will is strongly endorsed in Western society even when freedom to act is severely restricted. However, incarcerated adolescents endorsed free will to a slightly lesser extent than their nonincarcerated counterparts from Rakos et al. (Behavior and Social Issues 17:20–39, 2008 ), while incarcerated and nonincarcerated adults offered equally strong endorsements. The comparable endorsement by adults is consistent with the hypothesis that the belief in agency is an evolutionary adaptation. The small decrease found for incarcerated adolescents may reflect the interaction between developmental factors and the expression of an evolutionary adaptation. Additionally, incarcerated adolescents and adults associated beliefs in free will with viewing punishment as a means of deterrence, rehabilitation, and retribution. Incarcerated adults, but not incarcerated adolescents, associated beliefs in free will with greater self-esteem and with an external locus of control. Finally, though both incarcerated adults and adolescents endorsed free will strongly, the former manifested the belief by emphasizing free agentic choice whereas the latter focused on the personal responsibility that is interwoven with free choice. The implications of these findings are discussed in the context of evolutionary, cultural, and developmental factors. (shrink)

Executive functions (EFs) and impulsivity are dimensions of self-regulation that are both related to psychopathology. However, self-report measures of impulsivity and laboratory EF tasks typically display small correlations, and existing research indicates that impulsivity and EFs may tap separate aspects of self-regulation that independently statistically predict psychopathology in adulthood. However, relationships between EFs, impulsivity, and psychopathology may be different in childhood compared to adulthood. Here, we examine whether these patterns hold in the baseline assessment of the Adolescent Brain and Cognitive (...) Development (ABCD) sample, a national sample of over 11,000 children (including 749 twin pairs) ages 9–10 years. We examine the phenotypic and genetic relationships among latent variables for different components of EFs and multiple facets of impulsivity. Additionally, we assess how EFs and impulsivity relate to composite measures and latent variables of psychopathology derived from parent report. EFs were weakly correlated with impulsivity, and the strength varied by impulsivity facet, emphasizing their separability. We did not identify significant genetic and environmental correlations between EFs and impulsivity. Moreover, controlling for their small relationships with each other, both EFs and some facets of impulsivity statistically predicted an Externalizing factor, attention problems, and social problems, and twin analyses suggested these relationships were genetic in origin. These findings indicate that EFs and impulsivity represent phenotypically and genetically separable aspects of self-regulation that are both transdiagnostic correlates of psychopathology in childhood. (shrink)

Although clinical ethics consultation is a high-stakes endeavor with an increasing prominence in health care systems, progress in developing standards for quality is challenging. In this article, we describe the results of a pilot project utilizing portfolios as an evaluation tool. We found that this approach is feasible and resulted in a reasonably wide distribution of scores among the 23 submitted portfolios that we evaluated. We discuss limitations and implications of these results, and suggest that this is a significant step (...) on the pathway to an eventual certification process for clinical ethics consultants. (shrink)

The authors of this article are previous or current members of the Clinical Ethics Consultation Affairs (CECA) Committee, a standing committee of the American Society for Bioethics and Humanities (ASBH). The committee is composed of seasoned healthcare ethics consultants (HCECs), and it is charged with developing and disseminating education materials for HCECs and ethics committees. The purpose of this article is to describe the educational research and development processes behind our teaching materials, which culminated in a case studies book called (...) A Case-Based Study Guide for Addressing Patient-Centered Ethical Issues in Health Care (hereafter, the Study Guide). In this article, we also enumerate how the Study Guide could be used in teaching and learning, and we identify areas that are ripe for future work. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Cet ouvrage de poche présente une traduction française en regard du texte grec du Contre les Galiléens de l’empereur Julien. Cette œuvre perdue en tradition directe est conservée à travers les citations qu’en donne Cyrille d’Alexandrie dans les dix livres de son Contre Julien qui réfutent le premier livre de l’empereur. Du deuxième livre, il ne subsiste que des fragments, soit tirés des neuf livres suivants de Cyrille transmis de manière indirecte et très lacunaire, en grec ou en syriaque, so...