Although the Ca2+‐dependent proteinase (calpain) system has been found in every vertebrate cell that has been examined for its presence and has been detected in Drosophila and parasites, the physiological function(s) of this system remains unclear. Calpain activity has been associated with cleavages that alter regulation of various enzyme activities, with remodeling or disassembly of the cell cytoskeleton, and with cleavages of hormone receptors. The mechanism regulating activity of the calpain system in vivo also is unknown. It has been proposed (...) that binding of the calpains to phospholipid in a cell membrane lowers the Ca2+ concentration, [Ca2+], required for the calpains to autolyze, and that autolysis converts an inactive proenzyme into an active protease. Recent studies, however, show that the calpains bind to specific proteins and not to phospholipids, and that binding to cell membranes does not affect the [Ca2+] required for autolysis. It seems likely that calpain activity is regulated by binding of Ca2+ to specific sites on the calpain molecule, with binding to each site eliciting a response (proteolytic activity, calpastatin binding, etc.) specific for that site. Regulation must also involve an, as yet, undiscovered mechanism that increases the affinity of the Ca2+‐binding sites for Ca2+. (shrink)

First Published in 1999. Routledge is an imprint of Taylor & Francis, an informa company.

Transgender and gender expansive (TGE) youth often seek a variety of gender-affirming healthcare services, including pubertal suppression and hormone therapy requiring that TGE youth and their parents participate in informed consent and decision making. While youth must demonstrate the ability to understand and appreciate treatment options, risks, benefits, and alternatives as well as make and express a treatment choice, standardized approaches to assess the capacity of TGE youth to consent or assent in clinical practice are not routinely used. This scoping (...) review identified the currently available data regarding adolescent capacity to consent to gender-affirming medical treatments. Articles relevant to assessing adolescent capacity for clinical decision-making were identified using OVID Medline, Web of Science, and PubMed. Articles were reviewed and thematically analyzed. Eight relevant articles were identified using three tools for measuring adolescent clinical decision-making capacity: Measure of Understanding, Measure of Competence, and MacArthur Competence Assessment Tool (MacCAT). These studies explored hypothetical treatment decisions, mental health treatment decisions, HIV treatment decisions, genetic testing decisions, and gender-affirming medical decisions. Only one study specifically examines the capacity of TGE youth to consent to medical treatments. Age was correlated with capacity in most, but not all studies. Other studies found cognitive measures (IQ, literacy, numeracy) may impact important aspects of capacity (understanding and reasoning). For clinicians caring for TGE youth, tools such as the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) may prove useful, in conjunction with consideration of youth developmental abilities and utilization of shared decision-making practices. A standardized, collaborative approach to assessing TGE youth capacity would benefit TGE youth and their parents, and allow clinicians to more easily resolve ethical concerns. (shrink)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

ABSTRACT With few exceptions, the effectiveness of continuing education mandates has been measured by self-report assessments of the professional psychologists who fulfill them. The present investigation provided a longitudinal look at the number of approved CE providers and the incidence of licensing board complaints across a succession of two-year cycles prior to, and following, the 2012 implementation of CE mandates in the State of Illinois. Findings showed a substantial increase in the number of CE providers across that time, though no (...) significant change in the incidence of licensing board complaints, suggesting that the increased availability of CE did not translate into lower complaint rates. Possible reasons for these findings are noted, and recommendations for future work are detailed in support of an evidence-based approach to CE that better articulates and aligns its objectives with its outcomes in an era of renewed accountability in the health professions. (shrink)

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

The scientific world-outlook is something quite different from natural science. The word “science” in its legitimate modern usage represents both a kind of knowledge and the method of obtaining that knowledge. By “science” we may mean an objective body of facts and relationships concerning the physical world and arrived at by the scientific method of observation and reasoning—preferably quantitative observation and mathematical reasoning: thus we may say that the law of constant proportions is a part of the science of chemistry. (...) But we may also use the word science to denote that scientific method which I have just mentioned: thus I may say that science is the key to the investigation of nature—or that some inaccurate or biased piece of work is unscientific. Science, in either of these senses, does not contain any world-outlook, for it is quite impersonal. Thus science in the first sense consists of certain statements and relationships e.g.—that sulphur is yellow, that Jupiter has eight satellites, that all solutions of acids in water conduct electricity; while the scientific method indicates the manner in which from the data of our sense-impressions we can infer statements and conclusions, such as the above, which will be found to represent the phenomena correctly. But a scientific world-outlook means something different, because it is a world -outlook, the attitude of a man or woman towards the whole of that of which he or she is conscious. (shrink)

Suppose that a school restricts student expression critical of homosexual conduct yet allows or actively supports student expression that promotes acceptance and tolerance of gays and lesbians. Can such a policy be justified if the anti-gay speech disrupts the educational environment of the school while the pro-gay speech does not? Or does the differential treatment of anti-gay and pro-gay speech constitute unconstitutional viewpoint discrimination because it distorts the marketplace of ideas within the school? Can viewpoint discrimination ever be justified on (...) the ground that anti-gay speech invades the rights of others under Tinker v. Des Moines Independent Community School District, 393 U.S. 503 (1969)? These were among the questions debated by Judges Reinhardt and Kozinski in the Ninth Circuit's now-vacated panel opinion in Harper v. Poway Unified School District, 445 F.3d 1166 (9th Cir. 2006), but their significance to the law of student speech is quite general. Courts are increasingly becoming concerned with the question of whether Tinker allows viewpoint-based restrictions of student speech, but so far jurists have not reached agreement on this question or even on the simpler question of what counts as viewpoint discrimination. This article attempts to clarify the emerging debate about the permissibility of viewpoint discrimination under Tinker and proposes modifications to the Tinker framework that would enable courts to deal more fruitfully with charges that school officials have imposed viewpoint-based restrictions on student speech. I argue that we should think of viewpoint discrimination as purposeful restriction of expression on the basis of governmental disagreement with the message. Tinker must be understood to bar purposeful viewpoint discrimination, but the conclusion that a school speech restriction constitutes purposeful viewpoint discrimination will come at the end rather than at the beginning of constitutional analysis. A school will never announce that it has restricted student speech on the basis of disagreement with the message; instead, it will claim that it has regulated speech to prevent harm. And this is something that schools (and the state more generally) may sometimes do - at least with sufficient justification. Tinker obviously contemplates the regulation of speech where necessary to prevent two specific sorts of harms - disruption to the school's mission and violations of the rights of other students - and so must require courts to distinguish between school speech restrictions based on impermissible ideological purposes and those based on the permissible purposes of preventing disruptions or violations of student rights. Tinker's substantial disruption test, I contend, should primarily be understood as a mechanism for helping courts to smoke out these impermissible purposes. (shrink)

Nurses’ religious beliefs influence their motivations and perspectives, including their practice of ethics in nursing care. When the impact of these beliefs is not recognized, great potential for unethical nursing care exists. Thus, this article examines how the theology of one religious tradition, Seventh-day Adventism (SDA), could affect nurses. An overview of SDA history and beliefs is presented, which explains why ‘medical missionary’ work is central to SDAs. Theological foundations that would permeate an SDA nurse’s view of the nursing metaparadigm (...) concepts of person, health, environment (i.e. community), and nursing (i.e. service) are presented. The ethical principles guiding SDA nurses (i.e. principled, case-based, and care ethics) and the implications of these theological foundations for nurses are noted in a case study. (shrink)

Early versions of satellite and radiosonde datasets suggested that the tropical surface had warmed more than the troposphere, while climate models consistently showed tropospheric amplification of surface warming in response to human-caused increases in greenhouse gases. We revisit such comparisons here using new observational estimates of surface and tropospheric temperature changes. We find that there is no longer a serious discrepancy between modeled and observed trends in the tropics. Our results contradict a recent claim that all simulated temperature trends in (...) the tropical troposphere are inconsistent with observations. This claim was based on the use of older radiosonde and satellite datasets and on two methodological errors: the neglect of observational trend uncertainties introduced by interannual climate variability and application of an inappropriate statistical “consistency test”.This emerging reconciliation of models and observations has two primary explanations. First, because of changes in the treatment of buoy and satellite information, new surface temperature datasets yield slightly reduced tropical warming relative to earlier versions. Second, recently developed satellite and radiosonde datasets now show larger warming of the tropical lower troposphere. In the case of a new satellite dataset from remote sensing systems, enhancedRSS warming is due to an improved procedure of adjusting for inter-satellite biases. When the RSS-derived tropospheric temperature trend is compared with four different observed estimates of surface temperature change, the surface warming is invariably amplified in the tropical troposphere, consistent with model results. Even if we use data from a second satellite dataset with smaller tropospheric warming than in remote sensing systems RSS, observed tropical lapse rates are not significantly different from those in all model simulations.Our results contradict a recent claim that all simulated temperature trends in the tropical troposphere and in tropical lapse rates are inconsistent with observations. This claim was based on the use of older radiosonde and satellite datasets and on two methodological errors: the neglect of observational trend uncertainties introduced by interannual climate variability and application of an inappropriate statistical “consistency test”. (shrink)

A wide variety of ontologies relevant to the biological and medical domains are available through the OBO Foundry portal, and their number is growing rapidly. Integration of these ontologies, while requiring considerable effort, is extremely desirable. However, heterogeneities in format and style pose serious obstacles to such integration. In particular, inconsistencies in naming conventions can impair the readability and navigability of ontology class hierarchies, and hinder their alignment and integration. While other sources of diversity are tremendously complex and challenging, agreeing (...) a set of common naming conventions is an achievable goal, particularly if those conventions are based on lessons drawn from pooled practical experience and surveys of community opinion. We summarize a review of existing naming conventions and highlight certain disadvantages with respect to general applicability in the biological domain. We also present the results of a survey carried out to establish which naming conventions are currently employed by OBO Foundry ontologies and to determine what their special requirements regarding the naming of entities might be. Lastly, we propose an initial set of typographic, syntactic and semantic conventions for labelling classes in OBO Foundry ontologies. Adherence to common naming conventions is more than just a matter of aesthetics. Such conventions provide guidance to ontology creators, help developers avoid flaws and inaccuracies when editing, and especially when interlinking, ontologies. Common naming conventions will also assist consumers of ontologies to more readily understand what meanings were intended by the authors of ontologies used in annotating bodies of data. (shrink)