Over the last decade, our appreciation of the importance of the nucleolus for cellular function has progressed from the ordinary to the extraordinary. We no longer think of the nucleolus as simply the site of ribosome production, or a dynamic subnuclear body noted by pathologists for its changes in size and shape with malignancy. Instead, the nucleolus has emerged as a key controller of many cellular processes that are fundamental to normal cell homeostasis and the target for dysregulation in many (...) human diseases; in some cases, independent of its functions in ribosome biogenesis. These extra‐nucleolar or new functions, which we term “non‐canonical” to distinguish them from the more traditional role of the nucleolus in ribosome synthesis, are the focus of this review. In particular, we explore how these non‐canonical functions may provide novel insights into human disease and in some cases new targets for therapeutic development. (shrink)

The Alternative Model of Personality Disorders integrates several theoretical models of personality functioning, including interpersonal theory. The interpersonal circumplex dimensions of warmth and dominance can be conceptualized as traits similar to those in AMPD Criterion B, but interpersonal theory also offers dynamic hypotheses about how these variables that change from moment to moment, which help to operationalize some of the processes alluded to in AMPD Criterion A. In the psychotherapy literature, dynamic interpersonal behaviors are thought to be critical for identifying (...) therapeutic alliance ruptures, yet few studies have examined moment-to-moment interpersonal behaviors that are associated with alliance ruptures at an idiographic level. The current study examined the concurrent and cross-lagged relationships between interpersonal behaviors and alliance ruptures within each session in the famous Gloria films. Interpersonal behaviors as well as alliance ruptures were calculated at half minute intervals for each dyad. We identified distinct interpersonal patterns associated with alliance ruptures for each session: Gloria ’s warmth was positively related with withdrawal ruptures concurrently in the session with Carl Rogers; Gloria’s dominance and coldness were related with increased confrontation ruptures in the session with Fritz Perls concurrently, while her coldness was also predicted by confrontation ruptures at previous moments; lastly, both Gloria’s dominance and Albert Ellis’s submissiveness were positively related with withdrawal ruptures. These interpersonal patterns demonstrated the promise of using AMPD dimensions to conceptualize momentary interpersonal processes related to therapy ruptures, as well as the clinical importance of attuning to repetitive, dyad-specific interpersonal cues of ruptures within each session. (shrink)

Introduction No consent for health and medical research is appropriate when the criteria for a waiver of consent are met, yet some ethics committees and data custodians still require informed consent. Methods A single-blind parallel-group randomised controlled trial: 1129 families of children born at a South Australian hospital were sent information explaining data linkage of childhood immunisation and hospital records for vaccine safety surveillance with 4 weeks to opt in or opt out by reply form, telephone or email. A subsequent (...) telephone interview gauged the intent of 1026 parents (91%) in relation to their actions and the sociodemographic differences between participants and non-participants in each arm. Results The participation rate was 21% (n=120/564) in the opt-in arm and 96% (n=540/565) in the opt-out arm (χ2 (1 df) = 567.7, p<0.001). Participants in the opt-in arm were more likely than non-participants to be older, married/de facto, university educated and of higher socioeconomic status. Participants in the opt-out arm were similar to non-participants, except men were more likely to opt out. Substantial proportions did not receive, understand or properly consider study invitations, and opting in or opting out behaviour was often at odds with parents' stated underlying intentions. Conclusions The opt-in approach resulted in low participation and a biased sample that would render any subsequent data linkage unfeasible, while the opt-out approach achieved high participation and a representative sample. The waiver of consent afforded under current privacy regulations for data linkage studies meeting all appropriate criteria should be granted by ethics committees, and supported by data custodians. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12610000332022. (shrink)

PurposeIn Western society, the measurement of weight is prioritized over a person’s bodily experience. Hermeneutic philosopher Gadamer warned against the emphasis on measurement, rather than experience, in the medical sciences. An examination of the complexity of the experience of weight provides the opportunity to shift focus from quantifying the connection between health and weight to the experience of the person being weighed.MethodsThis qualitative hermeneutic study aims to understand people’s experiences of weight from the interviews of professionals and lay experts. Interviews (...) were analyzed using an interpretive hermeneutic method.ResultsThe interviews revealed that weight was experienced as a number imbued with meaning and bias, as a number that could be manipulated, and as a constant and anticipated bodily change. Weight change was expected and often unwelcomed, despite weight being a quality of the body that is always in flux. External measures of weight meant to monitor wellness and health inadvertently became an unhealthy fixation that prevented some participants from fully participating in life events and appreciating the stages their bodies were in.ConclusionWeight change is a necessary condition of being human, and bodies are and will be constantly changing. To achieve health and harmony, one must fit together the acceptance of change and their bodily experience of weight. It is often the preoccupation with weight, not weight itself, that gets in the way of living. (shrink)

Calls for public engagement on emerging agricultural technologies, including genetic engineering of farm animals, have resulted in the development of information that people can interact and engage with online, including “Frequently Asked Questions” (FAQs) developed by organizations seeking to inform or influence the debate. We conducted a frame analysis of FAQs webpages about genetic engineering of farm animals developed by different organizations to describe how questions and answers are presented. We categorized FAQs as having a regulatory frame (emphasizing or challenging (...) the adequacy of regulations), an efficiency frame (emphasizing precision and benefits), a risks and uncertainty frame (emphasizing unknown outcomes), an animal welfare frame (emphasizing benefits for animals) or an animal dignity frame (considering the inherent value of animals). Animals were often featured as the object of regulations in FAQs, and questions about animals were linked to animal welfare regulations. The public were represented using a variety of terms (public, consumer) and pronouns (I, we). Some FAQs described differences between technology terms (gene editing, genetic modification) and categorized technologies as either well-established or novel. This framing of the technology may not respond to actual public concerns on the topic. Organizations seeking to use FAQs as a public engagement tool might consider including multiple viewpoints and actual questions people have about genetic engineering. (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)

0 0 1 152 943 Lewis & Clark College 21 2 1093 14.0 Normal 0 false false false EN-US JA X-NONE Regarding each philosophy as a variation of that of Spinoza , t his article compares the German Idealism of Schelling and Hegel with the Indian Ved ā nta of Śaṅkara and Rāmānuja, as well as Abhinavagupta’s Kaśmiri Śaivism. It argues that only Hegel’s philosophy does not fail. For Śaṅkara, Rāmānuja, Abhinavagupta, and Schelling, the experience of ultimate reality—Brahman for Śaṅkara (...) and Rāmānuja, Śiva for Abhinavagupta, the Absolute for Schelling—is self-authenticating and so excludes the possibility of error. However, there is also no possibility of truth as no criterion distinguishes truth from error when individuals make contradictory claims. By contrast, Hegel’s Geist is an extended mind that potentially encompasses the human community. Geist develops historically. Experience is conceptual and concepts must be socially recognized to be legitimate. Experience is fallible, for Hegel, and better accounts are obtained through mutual criticism. Although disagreement represents an impassible impasse for Śaṅkara, Rāmānuja , Abhinavagupta, and Schelling, it is the road forward for Hegel. (shrink)

This article addresses the issue of properly assenting children with psychotic disorders to participate in clinical research. Due to the protective concerns with such a vulnerable population, additional precautions are necessary to ensure that youth with psychotic disorders assent to research with an appropriate level of understanding regarding study procedures. Current literature suggests that positive/negative symptoms and minor cognitive deficits do not interfere with the ability to comprehend study-related information for adults with psychosis if the study information is presented through (...) an educative process. Similarly, youth benefit from repeated presentation of procedures and periodic assessment of their comprehension. An integrated educative process is proposed that emphasizes the importance of an interactive consent through repetition and participant/investigator feedback. (shrink)

We welcome Ballantyne & Schaefer’s discussion of the issues concerning consent and use of health data for research. In response to their acknowledgement of the need for public debate and discussion, we provide evidence from our own public consultation on this topic.

Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are (...) extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity. (shrink)

Background: Clinical genomic implementation studies pose challenges for informed consent. Consent forms often include complex language and concepts, which can be a barrier to diverse enrollment, and these studies often blur traditional research-clinical boundaries. There is a move toward self-directed, web-based research enrollment, but more evidence is needed about how these enrollment approaches work in practice. In this study, we developed and evaluated a literacy-focused, web-based consent approach to support enrollment of diverse participants in an ongoing clinical genomic implementation study. (...) Methods: As part of the Cancer Health Assessments Reaching Many (CHARM) study, we developed a web-based consent approach that featured plain language, multimedia, and separate descriptions of clinical care and research activities. CHARM offered clinical exome sequencing to individuals at high risk of hereditary cancer. We interviewed CHARM participants about their reactions to the consent approach. We audio recorded, transcribed, and coded interviews using a deductively and inductively derived codebook. We reviewed coded excerpts as a team to identify overarching themes. Results: We conducted 32 interviews, including 12 (38%) in Spanish. Most (69%) enrolled without assistance from study staff, usually on a mobile phone. Those who completed enrollment in one day spent an average of 12 minutes on the consent portion. Interviewees found the information simple to read but comprehensive, were neutral to positive about the multimedia support, and identified increased access to testing in the study as the key difference from clinical care. Conclusions: This study showed that interviewees found our literacy-focused, web-based consent approach acceptable; did not distinguish the consent materials from other online study processes; and valued getting access to testing in the study. Overall, conducting empirical bioethics research in an ongoing clinical trial was useful to demonstrate the acceptability of our novel consent approach but posed practical challenges. (shrink)

Over 40 years of research have shown that traumatic brain injury affects brain volume. However, technical and practical limitations made it difficult to detect brain volume abnormalities in patients suffering from chronic effects of mild or moderate traumatic brain injury. This situation improved in 2006 with the FDA clearance of NeuroQuant®, a commercially available, computer-automated software program for measuring MRI brain volume in human subjects. More recent strides were made with the introduction of NeuroGage®, commercially available software that is based (...) on NeuroQuant® and extends its utility in several ways. Studies using these and similar methods have found that most patients with chronic mild or moderate traumatic brain injury have brain volume abnormalities, and several of these studies found—surprisingly—more abnormal enlargement than atrophy. More generally, 102 peer-reviewed studies have supported the reliability and validity of NeuroQuant® and NeuroGage®. Furthermore, this updated version of a previous review addresses whether NeuroQuant® and NeuroGage® meet the Daubert standard for admissibility in court. It concludes that NeuroQuant® and NeuroGage® meet the Daubert standard based on their reliability, validity, and objectivity. Due to the improvements in technology over the years, these brain volumetric techniques are practical and readily available for clinical or forensic use, and thus they are important tools for detecting signs of brain injury. (shrink)

This is a collection of the key articles written by renowned Wittgenstein scholar, G.P. Baker, on Wittgenstein’s later philosophy, published posthumously. Following Baker’s death in 2002, the volume has been edited by collaborator and partner, Katherine Morris. Contains articles previously only available in other languages, and one previously unpublished paper. Completely distinct from the widely-known work Baker did with P.M.S. Hacker in the Analytical Commentary on the Philosophical Investigations.

This is a collection of the key articles written by renowned Wittgenstein scholar, G.P. Baker, on Wittgenstein’s later philosophy, published posthumously. Following Baker’s death in 2002, the volume has been edited by collaborator and partner, Katherine Morris. Contains articles previously only available in other languages, and one previously unpublished paper. Completely distinct from the widely-known work Baker did with P.M.S. Hacker in the Analytical Commentary on the Philosophical Investigations.

BackgroundAustralian health and medical research funders support substantial research efforts, and incentives within grant funding schemes influence researcher behaviour. We aimed to determine to what extent Australian health and medical funders incentivise responsible research practices.MethodsWe conducted an audit of instructions from research grant and fellowship schemes. Eight national research grants and fellowships were purposively sampled to select schemes that awarded the largest amount of funds. The funding scheme instructions were assessed against 9 criteria to determine to what extent they incentivised (...) these responsible research and reporting practices: publicly register study protocols before starting data collection, register analysis protocols before starting data analysis, make study data openly available, make analysis code openly available, make research materials openly available, discourage use of publication metrics, conduct quality research, collaborate with a statistician, and adhere to other responsible research practices. Each criterion was answered using one of the following responses: “Instructed”, “Encouraged”, or “No mention”.ResultsAcross the 8 schemes from 5 funders, applicants were instructed or encouraged to address a median of 4 of the 9 criteria. Three criteria received no mention in any scheme. Importantly, most incentives did not seem strong as applicants were only instructed to register study protocols, discourage use of publication metrics and conduct quality research. Other criteria were encouraged but were not required.ConclusionsFunders could strengthen the incentives for responsible research practices by requiring grant and fellowship applicants to implement these practices in their proposals. Administering institutions could be required to implement these practices to be eligible for funding. Strongly rewarding researchers for implementing robust research practices could lead to sustained improvements in the quality of health and medical research. (shrink)

Analysis of Emmy Noether's 1918 theorems provides an illuminating method for testing the consequences of coordinate generality, and for exploring what else must be added to this requirement in order to give general covariance its far-reaching physical significance. The discussion takes us through Noether's first and second theorems, and then a third related theorem due originally to F. Klein. Contact will also be made with the contributions of, principally, J.L. Anderson, A. Trautman, P.A.M. Dirac, R. Torretti and the father of (...) the whole business, A. Einstein. (shrink)

Feature selection is a widely studied technique whose goal is to reduce the dimensionality of the problem by removing irrelevant features. It has multiple benefits, such as improved efficacy, efficiency and interpretability of almost any type of machine learning model. Feature selection techniques may be divided into three main categories, depending on the process used to remove the features known as Filter, Wrapper and Embedded. Embedded methods are usually the preferred feature selection method that efficiently obtains a selection of the (...) most relevant features of the model. However, not all models support an embedded feature selection that forces the use of a different method, reducing the efficiency and reliability of the selection. Neural networks are an example of a model that does not support embedded feature selection. As neural networks have shown to provide remarkable results in multiple scenarios such as classification and regression, sometimes in an ensemble with a model that includes an embedded feature selection, we attempt to embed a feature selection process with a general-purpose methodology. In this work, we propose a novel general-purpose layer for neural networks that removes the influence of irrelevant features. The Feature-Aware Drop Layer is included at the top of the neural network and trained during the backpropagation process without any additional parameters. Our methodology is tested with 17 datasets for classification and regression tasks, including data from different fields such as Health, Economic and Environment, among others. The results show remarkable improvements compared to three different feature selection approaches, with reliable, efficient and effective results. (shrink)

An important technique in large cardinal set theory is that of extending an elementary embedding j: M → N between inner models to an elementary embedding j*: M[G] → N[G*] between generic extensions of them. This technique is crucial both in the study of large cardinal preservation and of internal consistency. In easy cases, such as when forcing to make the GCH hold while preserving a measurable cardinal (via a reverse Easton iteration of α-Cohen forcing for successor cardinals α), the (...) generic G* is simply generated by the image of G. But in difficult cases, such as in Woodin's proof that a hypermeasurable is sufficient to obtain a failure of the GCH at a measurable, a preliminary version of G* must be constructed (possibly in a further generic extension of M[G]) and then modified to provide the required G*. In this article we use perfect trees to reduce some difficult cases to easy ones, using fusion as a substitute for distributivity. We apply our technique to provide a new proof of Woodin's theorem as well as the new result that global domination at inaccessibles (the statement that d (κ) is less than 2κ for inaccessible κ, where d (κ) is the dominating number at κ) is internally consistent, given the existence of 0#. (shrink)

Analysis of Emmy Noether’s 1918 theorems provides an illuminating method for testing the consequences of “coordinate generality”, and for exploring what else must be added to this requirement in order to give general covariance its far-reaching physical significance. The discussion takes us through Noether’s first and second theorems, and then a third related theorem due originally to F. Klein. Contact will also be made with the contributions of, principally, J.L. Anderson, A. Trautman, P.A.M. Dirac, R. Torretti and the father of (...) the whole business, A. Einstein (an apparent shift in Einstein’s thinking on the significance of general covariance between 1916 and 1918 is highlighted). (shrink)

The theory of mental models and its computer implementations have led to crucial experiments showing that no standard logic—the sentential calculus and all logics that include it—can underlie human reasoning. The theory replaces the logical concept of validity (the conclusion is true in all cases in which the premises are true) with necessity (conclusions describe no more than possibilities to which the premises refer). Many inferences are both necessary and valid. But experiments show that individuals make necessary inferences that are (...) invalid, e.g., Few people ate steak or sole; therefore, few people ate steak. Other crucial experiments show that individuals reject inferences that are not necessary but valid, e.g., He had the anesthetic or felt pain, but not both; therefore, he had the anesthetic or felt pain, or both. Nothing in logic can justify the rejection of a valid inference: a denial of its conclusion is inconsistent with its premises, and inconsistencies yield valid inferences of any conclusions whatsoever including the one denied. So inconsistencies are catastrophic in logic. In contrast, the model theory treats all inferences as defeasible (nonmonotonic), and inconsistencies have the null model, which yields only the null model in conjunction with any other premises. So inconsistences are local. Which allows truth values in natural languages to be much richer than those that occur in the semantics of standard logics; and individuals verify assertions on the basis of both facts and possibilities that did not occur. (shrink)

What makes the words we speak mean what they do? Possible-worlds semantics articulates the view that the meanings of words contribute to determining, for each sentence, which possible worlds would make the sentence true, and which would make it false. M. J. Cresswell argues that the non-semantic facts on which such semantic facts supervene are facts about the causal interactions between the linguistic behaviour of speakers and the facts in the world that they are speaking about, and that the kind (...) of causation involved is best analysed using David Lewis's account of causation in terms of counterfactuals. Although philosophers have worked on the question of the connection between meaning and linguistic behaviour, it has mostly been without regard to the work done in possible-world semantics and Language in the World is a book-length examination of this problem. (shrink)

We consider the desirability, or otherwise, of various forms of induction in the light of certain principles and inductive methods within predicate uncertain reasoning. Our general conclusion is that there remain conflicts within the area whose resolution will require a deeper understanding of the fundamental relationship between individuals and properties.

It was an empirical discovery that Phosphorus is Hesperus. According to Kripke, this was also the discovery of a necessary fact. Now, given Kripke’s theory of direct reference one could wonder what kind of discovery this is. For we already knew Phosphorus/Hesperus, and we also knew that any entity is, necessarily, identical to itself. So what is it that was discovered? I want to show that there is more to this widely known case than what usual readings, and critics, reveal; (...) and I want to show this under the Kripkean pattern that what was discovered is the plain fact of identity that Phosphorus is, and necessarily is, Hesperus. Moreover, I will show how both Kripkean theses, the necessity of identity and the direct theory of reference, should not be kept apart to understand the kind of discovery this is. In particular, understanding the kind of discovery we made will help us see how intuition is displayed in metaphysics, and how metaphysical impossibilities, and metaphysical modality in general, can be discerned by reason and separated from other modalities. The study of this discovery will help us see, in a line, how identity belongs to the inner and most profound structure of reality and to the most profound structure of cognition and language. (shrink)

In On the Origin of Species, Charles Darwin put forward his theory of natural selection. Conventionally, Darwin's argument for this theory has been understood as based on an analogy with artificial selection. But there has been no consensus on how, exactly, this analogical argument is supposed to work – and some suspicion too that analogical arguments on the whole are embarrassingly weak. Drawing on new insights into the history of analogical argumentation from the ancient Greeks onward, as well as on (...) in-depth studies of Darwin's public and private writings, this book offers an original perspective on Darwin's argument, restoring to view the intellectual traditions which Darwin took for granted in arguing as he did. From this perspective come new appreciations not only of Darwin's argument but of the metaphors based on it, the range of wider traditions the argument touched upon, and its legacies for science after the Origin. (shrink)

Abstract: Retama raetam (RR) is a traditional medicinal plant belongs to fabaceae family which grows in North Africa and East Mediterranean region. Locally, RR is used in several diseases including diabetes mellitus and hypertension. Thus, this study aims to investigate certain behavioral and central effects of methanolic extract of RR seeds in experimental animals (male Albino adult mice of 20 – 35 gm). Three exploratory behavioral models are used in this study, open field, elevated plus maze and light-dark box models, (...) in addition, picrotoxin induced seizure model in mice. In elevated plus-maze test of anxiety, a dose of 25 mg/kg of RR induced a significant increase in number of open arms entries and time spent on open arms of the maze compared to the control. In light-dark model, time spent on light area and number of light-dark transitions are significantly increased after treatment with 25 mg/kg RR extract of seeds. Open field model also revealed a significant increase in general motor activity of the mouse after 25 mg/kg of RR. On the other hand, a dose of 50 mg/kg of RR significantly induced a profound central and peripheral analgesic responses. In summary, this study concludes that RR seeds have a profound anxiolytic-like effect and analgesic response with delay in latency time of seizure induced by picrotoxin in mice. (shrink)