Integrating concepts of maintenance and of origins is essential to explaining biological diversity. The unified theory of evolution attempts to find a common theme linking production rules inherent in biological systems, explaining the origin of biological order as a manifestation of the flow of energy and the flow of information on various spatial and temporal scales, with the recognition that natural selection is an evolutionarily relevant process. Biological systems persist in space and time by transfor ming energy from one state (...) to another in a manner that generates structures which allows the system to continue to persist. Two classes of energetic transformations allow this; heat-generating transformations, resulting in a net loss of energy from the system, and conservative transformations, changing unusable energy into states that can be stored and used subsequently. All conservative transformations in biological systems are coupled with heat-generating transformations; hence, inherent biological production, or genealogical proesses, is positively entropic. There is a self-organizing phenomenology common to genealogical phenomena, which imparts an arrow of time to biological systems. Natural selection, which by itself is time-reversible, contributes to the organization of the self-organized genealogical trajectories. The interplay of genealogical (diversity-promoting) and selective (diversity-limiting) processes produces biological order to which the primary contribution is genealogical history. Dynamic changes occuring on times scales shorter than speciation rates are microevolutionary; those occuring on time scales longer than speciation rates are macroevolutionary. Macroevolutionary processes are neither redicible to, nor autonomous from, microevolutionary processes. (shrink)

What determines whether an action is right or wrong? Morality, Rules, and Consequences: A Critical Reader explores for students and researchers the relationship between consequentialist theory and moral rules. Most of the chapters focus on rule consequentialism or on the distinction between act and rule versions of consequentialism. Contributors, among them the leading philosophers in the discipline, suggest ways of assessing whether rule consequentialism could be a satisfactory moral theory. These essays, all of which are previously unpublished, provide students in (...) moral philosophy with essential material and ask key questions on just what the criteria for an adequate moral theory might be. (shrink)

Background: The factors influencing parents’ willingness to enroll their children in biobanks are poorly understood. This study sought to assess parents’ willingness to enroll their children, and their perceived benefits, concerns, and information needs under different consent and data-sharing scenarios, and to identify factors associated with willingness. Methods: This large, experimental survey of patients at the 11 eMERGE Network sites used a disproportionate stratified sampling scheme to enrich the sample with historically underrepresented groups. Participants were randomized to receive one of (...) three consent and data-sharing scenarios. Results: In total, 90,000 surveys were mailed and 13,000 individuals responded (15.8% response rate). 5737 respondents were parents of minor children. Overall, 55% (95% confidence interval 50–59%) of parents were willing to enroll their youngest minor child in a hypothetical biobank; willingness did not differ between consent and data-sharing scenarios. Lower educational attainment, higher religiosity, lower trust, worries about privacy, and attitudes about benefits, concerns, and information needs were independently associated with less willingness to allow their child to participate. Of parents who were willing to participate themselves, 25% were not willing to allow their child to participate. Being willing to participate but not willing to allow one’s child to participate was independently associated with multiple factors, including race, lower educational attainment, lower annual household income, public health care insurance, and higher religiosity. Conclusions: Fifty-five percent of parents were willing to allow their youngest minor child to participate in a hypothetical biobank. Building trust, protecting privacy, and addressing attitudes may increase enrollment and diversity in pediatric biobanks. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (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)

The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is (...) rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules. (shrink)

Monoclonal antibodies are essential biomedical research and clinical reagents that are produced by companies and research laboratories. The NIAID ImmPort (Immunology Database and Analysis Portal) resource provides a long-term, sustainable data warehouse for immunological data generated by NIAID, DAIT and DMID funded investigators for data archiving and re-use. A variety of immunological data is generated using techniques that rely upon monoclonal antibody reagents, including flow cytometry, immunofluorescence, and ELISA. In order to facilitate querying, integration, and reuse of data, standardized terminology (...) for describing monoclonal antibody reagents and their targets needs to be used for annotating data submitted to ImmPort. (shrink)

Although the neoconservative movement has come to dominate American conservatism, this movement has its origins in the old Marxist Left. Communists in their younger days, as the founders of neoconservatism, inverted Marxist doctrine by arguing that moral values and not economic forces were the primary movers of history. Yet the neoconservative critique of biotechnology still borrows heavily from Karl Marx and owes more to the German philosopher Martin Heidegger than to the Scottish philosopher and political economist Adam Smith. Loath (...) to identify these sources - or perhaps unaware of them - neoconservatives do not acknowledge these intellectual underpinnings or their implications. Thus, in the final analysis, their critique is incoherent and even internally inconsistent. By not acknowledging and embracing their intellectual roots, neoconservatives are left with a deeply ambivalent and often confused view of biotechnology and the society that gives rise to it. (shrink)

The paper discusses regularisation of dualities. A given duality between (concrete) categories, e.g. a variety of algebras and a category of representation spaces, is lifted to a duality between the respective categories of semilattice representations in the category of algebras and the category of spaces. In particular, this gives duality for the regularisation of an irregular variety that has a duality. If the type of the variety includes constants, then the regularisation depends critically on the location or absence of constants (...) within the defining identities. The role of schizophrenic objects is discussed, and a number of applications are given. Among these applications are different forms of regularisation of Priestley, Stone and Pontryagin dualities. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

We present a population density and moment-based description of the stochastic dynamics of domain $${\text{Ca}}^{2+}$$ -mediated inactivation of L-type $${\text{Ca}}^{2+}$$ channels. Our approach accounts for the effect of heterogeneity of local $${\text{Ca}}^{2+}$$ signals on whole cell $${\text{Ca}}^{2+}$$ currents; however, in contrast with prior work, e.g., Sherman et al. :985–995, 1990), we do not assume that $${\text{Ca}}^{2+}$$ domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain model (...) of an L-type $${\text{Ca}}^{2+}$$ channel introduced by Greenstein and Winslow :2918–2945, 2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell $${\text{Ca}}^{2+}$$ current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of $${\text{Ca}}^{2+}$$ inactivation that may occur via slow heterogeneous domain [ $${\text{Ca}}^{2+}$$ ]. Next, we find that when channel permeability is held constant, $${\text{Ca}}^{2+}$$ -mediated inactivation of L-type channels increases as the domain time constant increases, because a slow domain collapse rate leads to increased mean domain [ $${\text{Ca}}^{2+}$$ ] near open channels; conversely, when the maximum domain [ $${\text{Ca}}^{2+}$$ ] is held constant, inactivation decreases as the domain time constant increases. Comparison of simulation results using population densities and moment equations confirms the computational efficiency of the moment-based approach, and enables the validation of two distinct methods of truncating and closing the open system of moment equations. In general, a slow domain time constant requires higher order moment truncation for agreement between moment-based and population density simulations. (shrink)

The U.S. Food and Drug Administration's rationale for supporting the development and approval of BiDil for heart failure specifically in black patients was based on under-powered, post hoc subgroup analyses of two relatively old trials , which were further complicated by substantial covariate imbalances between racial groups. Indeed, the only statistically significant difference observed between black and white patients was found without any adjustment for potential confounders in samples that were unlikely to have been adequately randomized. Meanwhile, because the accepted (...) baseline therapy for heart failure has substantially improved since these trials took place, their results cannot be combined with data from the more recent trial amongst black patients alone. There is therefore little scientific evidence to support the approval of BiDil only for use in black patients, and the FDA's rationale fails to consider the ethical consequences of recognizing racial categories as valid markers of innate biological difference, and permitting the development of group-specific therapies that are subject to commercial incentives rather than scientific evidence or therapeutic imperatives. This paper reviews the limitations in the scientific evidence used to support the approval of BiDil only for use in black patients; calls for further analysis of the V-HeFT I and II data which might clarify whether responses to H-I vary by race; and evaluates the consequences of commercial incentives to develop racialized medicines. We recommend that the FDA revise the procedures they use to examine applications for race-based therapies to ensure that these are based on robust scientific claims and do not undermine the aims of the 1992 Revitalization Act. (shrink)

It is quite commonly held nowadays that universalizability is a purely formal feature of moral terms, or perhaps of moral rules.To say that something is good, it is asserted, implies that anything else with the same characteristics is also good; to say that Jones ought to do X is to commit oneself to saying that, in the same circumstances, Smith ought to do X. In pointing this out, it is suggested, one is not oneself taking up a moral position, (...) or laying down a particular moral rule, but simply making it clear what a moral utterance is. The principle ofuniversalizability is thus a principle of meta-ethics, not of morality itself. That moral judgments are universalizable, Hare tells us, is an analytic statement: “analytic by virtue of the meaning of the word moral”. (shrink)

The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or ‘ontologies’. Unfortunately, the very success of this approach has led to a proliferation of ontologies which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium has set in train a strategy to overcome this problem. Existing (...) OBO ontologies, including the Gene Ontology, are undergoing a process of coordinated reform and new ontologies being created on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable, logically well-formed, and to incorporate accurate representations of biological reality. We describe the OBO Foundry initiative, and provide guidelines for those who might wish to become involved. (shrink)

This book is unique in presenting an interdisciplinary conversation between jurists and logicians. It brings together scholars from both law and philosophy and looks at the application of 'the new logics' to law and legal ordering, in a number of legal systems. The first Part explores the ways in which the new logics shed light on the functioning of legal orders, including the structure of legal argumentation and the rules of evidence. The second addresses how non-classical logics can help us (...) to understand the interactions between multiple legal orders, in a range of contexts including domestic and international law. The final Part examines particular issues in the applicability of non-classical logics to legal reasoning. This book will be of interest to jurisprudence and logic scholars and students who want to deepen their understanding of relationships between law and legal reasoning, and learn about recent developments in formal logic. (shrink)

Wolfson, using literary analysis, produced an excellent study of the mystical views of Rabbi Menahem Mendel Schneerson, the last Lubavich Rebbe. This work should serve as paradigmatic for the study of Jewish mystical thought.

Background Unit-based critical care nurse leaders (UBCCNL) play a role in exemplifying ethical leadership, addressing moral distress, and mitigating contributing factors to moral distress on their units. Despite several studies examining the experience of moral distress by bedside nurses, knowledge is limited regarding the UBCCNL’s experience. Research aim The aim of this study was to gain a deeper understanding of the lived experiences of Alabama UBCCNLs regarding how they experience, cope with, and address moral distress. Research design A qualitative descriptive (...) design and inductive thematic analysis guided the investigation. A screening and demographics questionnaire and a semi-structured interview protocol were the tools of data collection. Participant and research context Data were collected from 10 UBCCNLs from seven hospitals across the state of Alabama from February to July 2023. Ethical considerations This study was approved by the Institutional Review Board at the University of Alabama in Huntsville. Informed consent was obtained from participants prior to data collection. Findings UBCCNLs experience moral distress frequently due to a variety of systemic and organizational barriers. Feelings of powerlessness tended to precipitate moral distress among UBCCNLs. Despite moral distress resulting in increased advocacy and empathy, UBCCNLs may experience a variety of negative responses resulting from moral distress. UBCCNLs may utilize internal and external mechanisms to cope with and address moral distress. Conclusions The UBCCNL’s experience of moral distress is not dissimilar from bedside staff; albeit, moral distress does occur as a result of the responsibilities of leadership and the associated systemic barriers that UBCCNLs are privier to. When organizations allocate resources for addressing moral distress, they should be convenient to leaders and staff. The UBCCNL perspective should be considered in the development of future moral distress measurement tools and interventions. Future research exploring the relationship between empathy and moral distress among nurse leaders is needed. (shrink)

The real history of the covey of attention-artists who call themselves "The Birds." A great deal of uncertainty--and even some genuine confusion--surrounds the origin, evolution, and activities of the so-called Avis Tertia or "Order of the Third Bird." Sensational accounts of this "attentional cult" emphasize histrionic rituals, tragic trance-addictions, and the covert dissemination of obscurantist ontologies of the art object. Hieratic, ecstatic, and endlessly evasive, the Order attracts sensual misfits and cabalistic aesthetes--both to its ranks, and to its scholarship. In (...) recent years, however, the revisionist work of the research collective ESTAR(SER) has done much to clear the air, bringing archival precision to the history of this covey of attention-artists who call themselves "The Birds." Gathering the best articles of the last twenty years of The Proceedings of ESTAR(SER), this volume represents a landmark in the history of aesthetic practices, and will be a point of departure for future work wading the muddy marshes at the limits of historicism."--Publisher description. (shrink)

We present a set of algorithms for automated simplification of symbolic constants of the form ∑iαixi with αi rational and xi complex. The included algorithms, called SimplifySum2 and implemented in Mathematica, remove redundant terms, attempt to make terms and the full expression real, and remove terms using repeated application of the multipair PSLQ integer relation detection algorithm. Also included are facilities for making substitutions according to user-specified identities. We illustrate this toolset by giving some real-world examples of its usage, including (...) one, for instance, where the tool reduced a symbolic expression of approximately 100 000 characters in size enough to enable manual manipulation to one with just four simple terms.2Available from https://github.com/alexkaiser/SimplifySum. (shrink)