Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participant's family. Yet investigators lack guidance on return of results to relatives, including after the participant's death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participant's death.

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research Consortium. The authors then (...) negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death. (shrink)

The translocation of tRNAs through the ribosome proceeds through numerous small steps in which tRNAs gradually shift their positions on the small and large ribosomal subunits. The most urgent questions are: (i) whether these intermediates are important; (ii) how the ribosomal translocase, the GTPase elongation factor G (EF‐G), promotes directed movement; and (iii) how the energy of GTP hydrolysis is coupled to movement. In the light of recent advances in biophysical and structural studies, we argue that intermediate states of translocation (...) are snapshots of dynamic fluctuations that guide the movement. In contrast to current models of stepwise translocation, kinetic evidence shows that the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction orchestrated by EF‐G and GTP hydrolysis. EF‐G combines the energy regimes of a GTPase and a motor protein and facilitates tRNA movement by a combination of directed Brownian ratchet and power stroke mechanisms. (shrink)

A common belief is that evolution generally proceeds towards greater complexity at both the organismal and the genomic level, numerous examples of reductive evolution of parasites and symbionts notwithstanding. However, recent evolutionary reconstructions challenge this notion. Two notable examples are the reconstruction of the complex archaeal ancestor and the intron‐rich ancestor of eukaryotes. In both cases, evolution in most of the lineages was apparently dominated by extensive loss of genes and introns, respectively. These and many other cases of reductive evolution (...) are consistent with a general model composed of two distinct evolutionary phases: the short, explosive, innovation phase that leads to an abrupt increase in genome complexity, followed by a much longer reductive phase, which encompasses either a neutral ratchet of genetic material loss or adaptive genome streamlining. Quantitatively, the evolution of genomes appears to be dominated by reduction and simplification, punctuated by episodes of complexification. (shrink)

Scale-free network models describe many natural and social phenomena. In particular, networks of interacting components of a living cell were shown to possess scale-free properties. A recent study(1) compares the system-level properties of metabolic and information networks in 43 archaeal, bacterial and eukaryal species and claims that the scale-free organization of these networks is more conserved during evolution than their content. BioEssays 24:105–109, 2002. Published 2002 Wiley Periodicals, Inc.

The adoption of the term grievance-fuelled violence reflects the fact that similarities exist between those committing violent acts in the context of grievance in different settings, so potentially allowing the application of insights gained in the study of one group to be applied to others. Given the low base rate of violence against public figures, studies in the field of violence against those in the public eye have tended to use, as a proxy for violence, attempts by the individuals concerned (...) to achieve unwarranted and unwanted proximity to the subject of their attention, given that approach is a necessary prerequisite for most forms of attack. In such studies, one factor that has frequently been considered is whether the making of threats is associated with a subsequent approach. The results have been varied, with no correlation found in some, a negative correlation in others, and a positive correlation in at least one. Such studies have been retrospective, using case files prepared for other purposes, and samples of cases have been selected according to their victims’ sector of employment – for instance, politicians, celebrities, judiciary, and the corporate world. This study of a sample of 126 threat assessment cases, using a prospective methodology, looks at the associations between the making of threats and subsequent approach from a different angle – that of a standardised and validated classification of underlying motivation. It finds that particular types and forms of threat are significantly associated with subsequent approach in cases that are fuelled by grievance, but not in those with the motivation of seeking a relationship. Furthermore, when a sample with a mixture of motivational categories was examined in the manner of previous studies, such associations with threat were not apparent. These results refine the existing understanding of the significance of threats in public-facing cases. Future research projects in this area might usefully incorporate the consideration of underlying motivation, in particular grievance. (shrink)

Theories of embodied cognition hypothesize interdependencies between psychological well-being and physical posture. The purpose of this study was to assess the feasibility of objectively measuring posture, and to explore the relationship between posture and affect and other patient centered outcomes in breast cancer survivors with persistent postsurgical pain over a 12-week course of therapeutic Qigong mind-body training. Twenty-one BCS with PPSP attended group Qigong training. Clinical outcomes were pain, fatigue, self-esteem, anxiety, depression, stress and exercise self-efficacy. Posture outcomes were vertical (...) spine and vertical head angles in the sagittal plane, measured with a 3D motion capture system in three conditions: eyes open, eyes open relaxed and eyes closed. Assessments were made before and after the Qigong training. The association between categorical variables was measured by Cramer’s V. In the EO condition, most participants who improved in fatigue and anxiety scales also had better vertical head values. For the EOR condition, a moderate correlation was observed between changes in vertical head angle and changes in fatigue scale. In the EC condition, most of the participants who improved in measures of fatigue also improved vertical head angle. Additionally, pain severity decreased while vertical spine angle improved. These preliminary findings support that emotion and other patient centered outcomes should be considered within an embodied framework, and that Qigong may be a promising intervention for addressing biopsychosocially complex interventions such as PPSP in BCSs. (shrink)

How to engage farmers that have limited formal education is at the foundation of environmentally-sound and equitable agricultural development. Yet there are few examples of curricula that support the co-development of knowledge with farmers. While transdisciplinary and participatory techniques are considered key components of agroecology, how to do so is rarely specified and few materials are available, especially those relevant to smallholder farmers with limited formal education in Sub-Saharan Africa. The few training materials that exist provide appropriate methods, such as (...) compost making, but do not explain relationships and synergies between nutrition, social inequalities, climate change and agroecology. Some food sovereignty and agroecology courses aim at popular political education for those with more formal education. Here we describe the process of development of an innovative curriculum, which integrates agroecology, nutrition, climate change, gender and other dimensions of social equity across 2 weeks of training explicitly for smallholders in southern Africa with limited formal education. The curriculum is highly participatory; we use concepts in popular education, transformative and experiential-based learning, and theatre. It is also integrative; we link agroecology with climate change, human and soil nutrition, gender, and related components of social equity. Developed in partnership with Malawian farmers, community development experts and academics from five countries, the curriculum was piloted with 520 smallholder farming households in Malawi and Tanzania, and evaluated using qualitative techniques. Clashes of language, cultural norms, and terminology were as great of a challenge as agreeing on and conveying technical information, to weave into a coherent whole. However, farmers who participated in the curriculum training demonstrated high interest, comprehension of material and interest in immediate application to their lives. (shrink)

BackgroundResponsive neurostimulation has been utilized as a treatment for intractable epilepsy. The RNS System delivers stimulation in response to detected abnormal activity, via leads covering the seizure foci, in response to detections of predefined epileptiform activity with the goal of decreasing seizure frequency and severity. While thalamic leads are often implanted in combination with cortical strip leads, implantation and stimulation with bilateral thalamic leads alone is less common, and the ability to detect electrographic seizures using RNS System thalamic leads is (...) uncertain.ObjectiveThe present study retrospectively evaluated fourteen patients with RNS System depth leads implanted in the thalamus, with or without concomitant implantation of cortical strip leads, to determine the ability to detect electrographic seizures in the thalamus. Detailed patient presentations and lead trajectories were reviewed alongside electroencephalographic analyses.ResultsAnterior nucleus thalamic leads, whether bilateral or unilateral and combined with a cortical strip lead, successfully detected and terminated epileptiform activity, as demonstrated by Cases 2 and 3. Similarly, bilateral centromedian thalamic leads or a combination of one centromedian thalamic alongside a cortical strip lead also demonstrated the ability to detect electrographic seizures as seen in Cases 6 and 9. Bilateral pulvinar leads likewise produced reliable seizure detection in Patient 14. Detections of electrographic seizures in thalamic nuclei did not appear to be affected by whether the patient was pediatric or adult at the time of RNS System implantation. Sole thalamic leads paralleled the combination of thalamic and cortical strip leads in terms of preventing the propagation of electrographic seizures.ConclusionThalamic nuclei present a promising target for detection and stimulation via the RNS System for seizures with multifocal or generalized onsets. These areas provide a modifiable, reversible therapeutic option for patients who are not candidates for surgical resection or ablation. (shrink)

Die Studie bemüht sich um eine Rekonstruktion des ästhetischen Denkens Goethes bis zur Weimarer Klassik. Im Untersuchungsgebiet zeichnen sich schon sehr früh Tendenzen zur Autonomisierung der Kunst- und Literaturtheorie ab. In Anlehnung an Pierre Bourdieus Konzept des literarischen Feldes werden paradigmatische theoretische Schriften einer intertextuellen Mikroanalyse unterzogen und zugleich sowohl mit den unmittelbaren Entstehungsumständen und künstlerischen Bezugspunkten, als auch v.a. mit ihren europäischen Kontexten in Beziehung gesetzt. Die Spezifik wie auch die Exemplarität der nicht-systematischen Ästhetik Goethes sind somit vor einem (...) erweiterten Horizont neu zu diskutieren. (shrink)

Volume 20 of _The Annual of Psychoanalysis_ ably traverses the analytic canvas with sections on "Theoretical Studies," "Clinical Studies," "Applied Psychoanalysis," and "Psychoanalysis and Philosophy." The first section begins with Arnold Modell's probing consideration of the paradoxical nature of the self, provocatively discussed with John Gedo. Modell focuses on the fact that the self is simultaneously public and private, dependent and autonomous. Alice Rosen Soref next explores innate motivation and self-protective regulatory processes from the standpoint of recent infancy research; her (...) notion of a lifelong two-track model of self and relatedness helps establish a normative baseline that can anchor psychoanalytic theory. George Mahl makes an interesting contribution to Freud studies in the form of a new chronology of Freud's works and the number of pages they contain in the _Standard Edition_. The section ends with Robert Galatzer-Levy and Mayer Gruber's "quasi-experiment about disgust." They test and disconfirm the hypothesis that disgust is an affective response to an abstract sense of disorder rather than a transformation of a concrete, bodily experience by systematically exploring references to concepts of disgust in the Old Testament. Section II, on "Clinical Studies," opens with Henry Smith's fascinating elaboration of Freud's notion of "screen memories" into a theory of screening that denotes the general process by which mental content is organized. He illustrates his thesis by invoking the "screen language" employed by a patient throughout her analysis. Ernest Wolf next explores the tension between being a "scientist" and a "healer" in Freud and his followers to illuminate struggles within the psychoanalytic movement and to help account for current attitudes toward abstinence, neutrality, and gratification. Kenneth Newman focuses on this same triptych of technical precepts. He argues, in the spirit of Winnicott and Kohut, that analysts can only alter the hostile internal environments of their patients by becoming "usable" objects and cultivating an optimally responsive analytic environment. A particularly rich collection of applied analytic studies forms Section III of the volume. Individual chapters focus on the childhood of Vincent van Gogh ; the psychological healing process depicted in George Eliot's _Silas Marner_ ; the self-psychological meaning of "blood brotherhood" in D. H. Lawrence's _Women in Love_ ; ecstatic mysticism in the 19th-century Indian saint Sri Ramakrishna ; the disintegration of the Tyrone family in Eugene O'Neill's _Long Day's Journey into Night_ ; and the nature and analytic significance of Freud's aesthetic response to Michelangelo's _Moses_. Finally, in Section IV, George Brook examines the commonsense psychological knowledge of everyday life, that is, the nonpsychoanalytic knowledge on which much of clinical psychoanalysis ultimately depends. Taken together, the four sections of Volume 20 of _The Annual_ offer an exciting overview of contemporary psychoanalysis. Section I highlights recent trends in psychoanalytic theorizing and the testing of psychoanalytic propositions; Section II explores the relevance of new theoretical perspectives to clinical work; Section III demonstrates the applicability of these new perspectives to psychobiographical and literary analysis; and Section IV provocatively explores the points of connection between everyday ideas and attitudes and the tenets of psychoanalytic practice. (shrink)

Volume 25 of _The Annual_ is dedicated to the memory of Michael Franz Basch, who achieved distinction as both a psychoanalytic theorist of the first rank and an authority on the nature and conduct of dynamic psychotherapy. A wide range of original contributions bear witness to his theoretical, clinical, and educational interests. A number of papers remind us of Basch's prominence as a self-psychological theorist: Elson's self-psychological reappraisal of self-pity, dependence, and manipulation as self-states; Ornstein's developmental perspective on power, self-esteem, (...) and destructive aggression; Tolpin's review of sexuality from the standpoint of normal self development; and Wolf's discussion of self psychology and the "aging self." Basch's life-long educational concerns gain expression in Goldberg's discussion of clinical teaching, particularly the challenge of leading of case conferences; and Ornstein's and Kay's thoughtful consideration of "enduring difficulties" in American medical education. Additional highlights of the volume include: Fawcett's consideration of the role of pharmacotherapy in psychodynamic treatment; Jaffe's consideration of the applicability of hierarchical models to assessment and intervention in brief psychotherapy; Galatzer-Levy's review of the "witch" metapsychology; Gedo's analysis of mythic themes in the operas _Don Giovanni_ and _Der Rosenkavalier_; Modell's reflections on metaphor and affects; and Kernberg's discussion of a "new psychoanalytic mainstream," which he compares and contrasts with a parallel convergence of Kohutian and interpersonal analytic approaches. Many of these contributions incorporate reflections on Basch as a teacher and colleague, and the entire volume is framed by Goldberg's moving tribute. Analysts and psychotherapists sharing Basch's commitment to academic and clinical excellence and his keen awareness of the pragmatic requirements of doing effective therapy will find in Volume 25 a cornucopia of riches. (shrink)

No consensus yet exists on how to handle incidental fnd-ings in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are fndings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers (...) have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed. (shrink)

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Книга предназначена для студентов, преподавателей и научных сотрудников высших учебных заведений, занимающихся вопросами философии.

Following up on a 1989 paper on the subject, this essay revisits the question of ethical expertise in the court room. Informed by recent developments in the use of ethics experts, the authors argue 1) that the adversarial nature of court proceedings challenges the integrity of the ethicist's pedagogical role; 2) that the use of ethics experts as normative authorities remains dubious; 3) that clarification of the State's interest in “protecting the ethical integrity of the medical profession” is urgently required; (...) and 4) that the expertise of the ethicist may be more appropriately used in advising the legislature than in influencing the court. (shrink)

Human genomics is a translational field spanning research, clinical care, public health, and direct-to-consumer testing. However, law differs across these domains on issues including liability, consent, promoting quality of analysis and interpretation, and safeguarding privacy. Genomic activities crossing domains can thus encounter confusion and conflicts among these approaches. This paper suggests how to resolve these conflicts while protecting the rights and interests of individuals sequenced. Translational genomics requires this more translational approach to law.