Background To describe the preferences for disclosure of individual biomarker results among mothers participating in a longitudinal birth cohort. Methods We surveyed 343 mothers that participated in the Health Outcomes and Measures of the Environment Study about their biomarker disclosure preferences. Participants were told that the study was measuring pesticide metabolites in their biological specimens, and that the health effects of these low levels of exposure are unknown. Participants were asked whether they wanted to receive their results and their child's (...) results. In addition, they were asked about their preferred method (letter vs in person) and format (more complex vs less complex) for disclosure of results. Results Almost all of the study participants wanted to receive their individual results (340/343) as well as their child's results (342/343). However, preferences for receiving results differed by education level. Mothers with less than a college degree preferred in-person disclosure of results more often than mothers with some college education or a college degree (34.3% vs 17.4% vs 7.9%, p<0.001). Similarly, mothers with less than a college education preferred a less complex disclosure format than mothers with some college education or a college degree (59.7% vs 79.1% vs 86.3%, p<0.0001). Conclusion While almost all study participants preferred to receive results of their individual biomarker tests, level of education was a key factor in predicting preferences for disclosure of biomarker results. To ensure effective communication of this information, disclosure of biomarker results should be tailored to the education level of the study participants. (shrink)

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and adult structures (...) solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

Abstract:Sustainable development and built heritage are oft-naturalized hegemonic discourses of the dominant social class. However, under the lens of critical sociomateriality, these categories destabilize—and in Brexit-era London, epicenter of a financial and technological capitalist circulatory space, “all that is solid melts” into the scopal regime of London's View Management Framework (LVMF). Analyzing multiple discourses of Southwark's Strata SE1— billed London's first “sustainable tower”—and adaptive reuse of the historically preserved Lambeth Water Tower, I argue that these structures constitute ‘interface objects’ in (...) a broader relational geography imbricating physical material, social objects, gentrification and the naturalized epistemologies of hegemonic development within London's skyline itself. I offer a reading of critical sociomateriality which illuminates rhythms of daily life within spatial-technological systems of energy provision, urban metabolic processes, as well as “hegemonic premiums,” what Richard Barras terms expected return on symbolic capital vis-à-vis the dominant panopticism of the LVMF. This paper contributes a theorization of critical sociomateriality, operating across a diversity of scales, tactics, and disciplines, analyzing discourses and practices which insinuate politics, artifacts, and technologies across contested issues. Critical sociomateriality is presented as a methodology for deconstructing tactics for inhabiting and interfacing with ‘sustainability’ through London's skyline in an unequal capitalist system marked by dissensus over runaway development, social precarity, and inequality in lived experiences of the urban environment. (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)

Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels in the (...) cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. (shrink)

Beginning in 2002, Wells Fargo began opening fraudulent accounts for unsuspecting customers. Stakeholders at every level either participated in, ignored, or tolerated the bank’s behavior that defrauded consumers on a massive scale. These unethical and well-documented schemes spanned more than a decade. Using public sources, this case recounts the events and ethical lapses that unfolded over the multiyear investigation of the Wells Fargo fraudulent accounts scandal and illuminates the general systemic failures of corporate culture and governance, public regulation, and market (...) responses to promote ethical business practices. This case provides the opportunity to consider what means for fostering ethical conduct might exist if a corporation can be big enough and rich enough that civil, criminal, regulatory, and market forces cannot deter unethical corporate practices, and if the market does not punish the corporation for a culture that promotes fraud. (shrink)

A community's abilities to promote health and maximize its response to public health threats require fulfillment of one of the four elements of public health legal preparedness, the capacity to effectively coordinate law-based efforts across different governmental jurisdictions, as well as across multiple sectors and disciplines. Government jurisdictions can be viewed “vertically” in that response efforts may entail coordination in the application of laws across multiple levels, including local, state, tribal, and federal governments, and even with international organizations. Coordination of (...) legal responses to public health emergencies also may involve a horizontal dimension comprising numerous and diverse sectors, such as public health, public and private health care, emergency management, education, law enforcement, the judiciary, and the military.Although responses to many acute health threats can implicate multiple jurisdictions and sectors, the jurisdictional and sectoral dimensions of legal preparedness are complex and may vary substantially by the nature of a threat, its geographic and geopolitical extent, and the operational response demanded. (shrink)

A community's abilities to promote health and maximize its response to public health threats require fulfillment of one of the four elements of public health legal preparedness, the capacity to effectively coordinate law-based efforts across different governmental jurisdictions, as well as across multiple sectors and disciplines. Government jurisdictions can be viewed “vertically” in that response efforts may entail coordination in the application of laws across multiple levels, including local, state, tribal, and federal governments, and even with international organizations. Coordination of (...) legal responses to public health emergencies also may involve a horizontal dimension comprising numerous and diverse sectors, such as public health, public and private health care, emergency management, education, law enforcement, the judiciary, and the military.Although responses to many acute health threats can implicate multiple jurisdictions and sectors, the jurisdictional and sectoral dimensions of legal preparedness are complex and may vary substantially by the nature of a threat, its geographic and geopolitical extent, and the operational response demanded. (shrink)

Direct-to-consumer genetic testing is a growing phenomenon, fuelled by the notion that knowledge equals control. One ethical question that arises concerns the proband’s duty to share information indicating genetic risks in their relatives. However, such duties are unenforceable and may result in the realisation of anticipated harm to relatives. We argue for a shift in responsibility from proband to provider, placing a duty on test providers in the event of identified actionable risks to relatives. Starting from Parker and Lucassen’s 'joint (...) account model', we adapt Kilbride’s application of the rule of rescue and balance it against the relative’s right not to know, placing responsibility on the providers of direct-to-consumer genetic testing. Where the risk of disease to a relative is actionable, we argue providers ought to share results even in the face of the proband’s objections. Confidentiality issues are navigated by a pre-emptive consent model, whereby consumers agree to the sharing of certain information with their relatives ahead of testing and as a condition of testing. When a relative is informed, the proband’s privacy is protected by maximal deidentification, and the rights of the relative are met by a stepwise approach to informing that allows them to decide how much information they receive. (shrink)

Late in 1990, the Center for the Study of Ethics in the Professions at Illinois Institute of Technology (lIT) received a grant of more than $200,000 from the National Science Foundation to try a campus-wide approach to integrating professional ethics into its technical curriculum.! Enough has now been accomplished to draw some tentative conclusions. I am the grant's principal investigator. In this paper, I shall describe what we at lIT did, what we learned, and what others, especially philosophers, can learn (...) from us. We set out to develop an approach that others could profitably adopt. I believe that we succeeded. (shrink)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by (...) a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. (shrink)

We investigated people's ability to infer others’ mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents’ desires throughout. When the agent observed, but did not cause the outcome, participants’ ability to recover the agent's beliefs depended on the evidence they got. When the agent caused the event, participants’ judgments also depended on the probability of the action ; when actions were improbable given the mental states, people failed to recover the agent's (...) beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout, consistent with the proposal that people rationally integrate information about others’ actions and emotional reactions to infer their unobservable mental states. (shrink)

Many epistemologists are enamored with a defeat condition on knowledge. In this paper we present some implementation problems for defeatism, understood along either internalist or externalist lines. We then propose that one who accepts a knowledge norm of belief, according to which one ought to believe only what one knows, can explain away much of the motivation for defeatism. This is an important result, because on the one hand it respects the plausibility of the intuitions about defeat shared by many (...) in epistemology; but on the other hand, it obviates the need to provide a unified account of defeat which plays well with the most plausible views of how knowledge fits with evidential probability. (shrink)

Various explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids—androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins—which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand‐based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and sex steroids (...) influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand‐based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones. BioEssays 25:396–400, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

We consider three accepted truths about iris biometrics, involving pupil dilation, contact lenses and template aging. We also consider a relatively ignored issue that may arise in system interoperability. Experimental results from our laboratory demonstrate that the three accepted truths are not entirely true, and also that interoperability can involve subtle performance degradation. All four of these problems affect primarily the stability of the match, or authentic, distribution of template comparison scores rather than the non-match, or imposter, distribution of scores. (...) In this sense, these results confirm the security of iris biometrics in an identity verification scenario. We consider how these problems affect the usability and security of iris biometrics in large-scale applications, and suggest possible remedies. (shrink)

This article addresses three interrelated concerns: the pervasive nature of technologically induced impatience, a theological understanding of divine patience, and, finally, a suitable response to techno-impatience by way of engagement with the art and practice of holy habit. As we have experienced faster flows of information, and larger amounts of information through which we must sort, we have become less patient people. This loss of patience continues to produce a new kind of personal and communal disquiet on an impressive scale. (...) To address concerns with techno-impatience, arguments will be drawn from scriptural and theological concepts of divine patience. These concepts prompt us to rediscover, and reinvent, a richer understanding of patience as an individuated spiritual virtue. Accordingly, a corrective to the exacerbating effects of technologically induced impatience will be offered: namely, the explicit spiritual discipline of practicing holy patience. (shrink)

Much progress has been made recently towards uncovering the mechanisms that control the size to which organisms and their organs grow, and identifying some of the genes responsible. Size control, however, is only half of the equation. In growing to the right size, tissues must also grow to the right shape. A recent paper1 suggests that a hitherto overlooked cellular behaviour governs the size and shape of a growing tissue, and issues a challenge to developmental biologists to identify the molecular (...) mechanisms involved. BioEssays 25:5–8, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Depression experienced by older adults is proving an increasing global health burden, with rates generally 7% and as high as 27% in the USA. This is likely to significantly increase in coming years as the number and proportion of older adults in the population rises all around the world. Therefore, it is imperative that the effectiveness of approaches to the prevention and treatment of depression are understood. Creative arts interventions, including art, dance movement, drama and music modalities, are utilised internationally (...) to target depression and depressive symptoms in older adults. This includes interventions led by trained arts therapists as well as other health and arts professionals. However, to date there has not been a systematic review that reports effects and examines the processes (why) and mechanisms (how) of creative arts interventions are used to address depression in this older age group. This systematic review of studies on creative arts interventions for older adults experiencing depression examined: outcomes of four creative arts modalities (art, dance movement, drama, and music); with particular attention paid to processes documented as contributing to change in each modality; and mechanisms considered to result from these processes. Our analysis of 75 articles (17 art, 13 dance, 4 drama and 41 music) indicates mostly significant quantitative or positive qualitative findings, particularly for interventions led by creative arts therapists. Mechanisms of change gleaned from the studies that were common across modalities include physical (e.g. increased muscle strength; neurochemical effects, such as endorphin release), intra-personal (e.g. enhanced self-concept, strengthened agency and mastery; processing and communication of emotions), cultural (e.g. creative expression, aesthetic pleasure), cognitive (e.g. stimulation of memory) and social (e.g. increased social skills and connection), that were all considered to contribute to reduced depression and symptoms. Recommendations for future research include a stronger focus on testing of processes and mechanisms. (shrink)

In 1995, the eyeless (ey) gene was dubbed the “master‐regulator” of eye development in Drosophila. Not only is ey required for eye development, but its misexpression can convert many other tissues into eye, including legs, wings and antennae.(1) ey is remarkable for its ability to drive coordinate differentiation of the multiple cell types that have to differentiate in a very precise pattern to construct the fly eye, and for its power to override the previous differentiation programs of many other diverse (...) tissues. Even more remarkable, the ey homolog Pax6 and homologs of other eye determination genes from Drosophila are also required for eye development in vertebrates,(2,3) prompting reassessment of the evolution of vision throughout the animal kingdom.(4,5) Now Kumar and Moses have published a study that throws a new light on ey function in Drosophila.(6) According to their work, ey becomes a master regulator of eye development much later than previously thought, and is regulated by signalling through the Notch and EGFR signaling pathways. BioEssays 23:763–766, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Abstract11β‐hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17β‐hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11β‐hydroxysteroid dehydrogenases and four mammalian 17β‐hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11β‐ and 17β‐hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with β‐hydroxybutyrate dehydrogenase, 11‐cis retinol dehydrogenase and retinol dehydrogenase; Type 3 17β‐hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional enzyme (...) on a fourth branch. Pig 17β‐hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17β‐hydroxysteroid dehydrogenase dehydrogenases; in which case, the evolution of 17β‐hydroxysteroid dehydrogenase activity is an example of functional convergence. The phylogeny also suggests that independent evolution of specificity toward C11 substituents on glucocorticoids and C17 substituents on androgens and estrogens has occurred in Types 1 and 2 11β‐ and 17β‐hydroxysteroid dehydrogenases. (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 study examines the ethical attitudes and practices of securities analysts and portfolio managers from four Pacific Rim countries – Hong Kong, Japan, Singapore and Thailand – and compares the findings to a similar study of North American investment professionals to identify significant differences. The findings show that many differences exist due to cultural differences and differences in the regulatory environment between the Pacific Rim countries studied and North America.

The author contends that the analogies between "the logical roles of singular and universal statements" are important but do not "justify the conclusion that singular statements are reducible to propositions" of the forms a, E, I, And o. (staff).

Sexual reproduction is a composite, not a singular, phenomenon and as such can be subdivided into a number of componentsi.e. fusion, recombination, fission, and the male-female phenomenon. These components can evolve independently, though any evolutionary change in one component is likely to influence the future evolution of the other components. The ambiguity that surrounds the term ‘sex’ due to a failure to recognise the composite nature of sexual reproduction has led to considerable confusion in past discussions of the evolution of (...) the phenomenon. This paper considers the possible chronological interaction of the components of sexual reproduction both with each other and with the sequence of selective pressures that seem likely to have acted. This chronological approach is used to consider: the origin of sexual reproduction; the evolution of sexual reproduction in the common ancestor of the procaryotes and eucaryotes; the modification of the ancestral system in the procaryote line following the procaryote-eucaryote dichotomy; and the modification of the ancestral system in the eucaryote line up to the origin of the male-female phenomenon.It is suggested that the fusion and recombination of the first living organisms were chronological continuations of the fusion and recombination of complex organic molecules that led up to the origin of life. The evolution of the third major component of sexual reproductioni.e. fission , by definition coincided with the origin of life. Initial selection on the components of sexual reproduction are likely to have been related to the optimum manifestations of size, complexity, diversity, multiplication, and distribution. Resultant early evolutionary trends are likely to have been: selective fusion between more-similar organisms; increase in number of fissions per fusion; and less recombination.The procaryote-eucaryote dichotomy is argued to have evolved in response to the increasing cellular problems of packing and replicating an increasing amount of hereditary material. The evolution of a single circular hereditary organelle in the procaryote line is argued to have led to the loss of total fusion and the specialisation of individuals into either donors or recipients. The donor-recipient phenomenon of procaryotes is directly analogous to the male-female phenomenon of eucaryotes and leads to parallel evolution due to sexual selection in both groups. In the eucaryote line the ancestral mechanism of sexual reproduction is argued to have persisted through, but to have been greatly modified by, the evolution of complex machinery for the handling of multiple hereditary organelles at cell division and reduction division. The evolutionary modification of the ancestral system of sexual reproduction is suggested to have led in eucaryotes to the evolution of: the species phenomenon; allelic recombination; and the male-female phenomenon. (shrink)

Patient safety has only recently been subjected to wide-spread systematic study. Healthcare differs from other high risk industries in being more diverse and multi-contextual, and less certain and regulated. Also many patient safety problems are low-frequency events associated with many, varied contributing factors. The subject of this paper is the epistemology of patient safety (the science of the method of finding out about patient safety). Patient safety research is considered here on the background of a risk management framework which requires (...) researchers to: • Understand the context - as a subset of healthcare quality, services and systems research, with technical and human behavioural (cultural) components and a range of external and internal organisational influences, a wide range of research disciplines is necessary • Identify the risks - identify the things that go wrong and the frequency and nature of different types of incidents from sources such as medical record review, observational studies, audit, incident and medico-legal reports • Analyse the risks - deconstruct the things that go wrong, identifying contributing factors and trying to detect trends and patterns in contributing factors, detection, mitigation factors, ameliorating factors and actions taken to reduce risk • Evaluate the risks - decide on priorities, identifying preventive and corrective strategies and judging the risk- and cost-benefit of potential corrective strategies such as standardisation or simplification of a process or device • Manage the risk - evaluate and scope preventive and/or corrective strategies and then implement these, or place the problem on a risk register pending solution, or accept that what is needed is unaffordable • Communicate and consult - use interactive sessions, audit, on-going feedback, reminders and patient mediated prompts • Monitor and review the state of the problem - get baseline trends and patterns so that changes can be tracked and properly attributed to an intervention A hierarchy of levels of evidence has been proposed for clinical research and we argue that insufficient weighting has been given to lower ranked levels of research and to qualitative research, although critical interpretive synthesis is now gaining acceptance in mainstream thinking (e.g. by the Cochrane Collaboration). Fundamental challenges remain including how to grasp the elusive concept of patient safety, how to quantify, characterise and cost the problems, how to judge the extent to which harm can be attributed to errors, violations or system failures, how to identify contributing factors and the extent to which they can be implicated, how to judge whether incidents or their precursors are preventable, how to generate strong evidence to make healthcare safer and how to translate research into practice. Future directions include addressing the mundane as well as rare, dramatic events, and developing further research in non-hospital settings and in developing countries. In summary, a mixture of qualitative and quantitative methods, using information from all available data sources and combining retrospective, real time and prospective study designs, is necessary to address some of the more difficult patient safety problems. (shrink)

Drawing on writers as diverse as Saul Kripke, Stanley Cavell, G. E. M. Anscombe, Jonathan Lear, and Bernard Williams, I offer an interpretation of Wittgenstein's key notion of a form of life that explains why Wittgenstein was so enigmatic about it. Then, I show how Hilary Putnam's criticism of Wittgenstein's philosophy of mathematics and Richard Rorty's support of (what he takes to be) Wittgenstein's legacy in the philosophy of mind both require mistaken assumptions about Wittgenstein's idea of a form of (...) life. Finally, I consider the extent to which the idea of a form of life is subject to Donald Davidson's critique of the idea of a conceptual scheme. (shrink)

dilemma, a dilemma concerning the individuation of psychological states that explain behavior. Beliefs are individuated by most functionahsts in terms of that 'that'-clauses; functional states are individuated 'narrowly' (i.e.