The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

The Multidimensional Religious Ideology (MRI) scale is a new 43-item measure that quantifies conservative versus liberal aspects of religious ideology. The MRI focuses on recurring features of ideology rooted in innate moral instincts while capturing salient differences in the ideological profiles of distinct groups and individuals. The MRI highlights how religious ideology differs from political ideology while maintaining a robust grounding in the social psychology of ideology generally. Featuring three major dimensions (religious beliefs, religious practices, and religious morality) and eight (...) subdimensions, the MRI is sensitive enough to generate novel insights into religious ideology across demographic groups and individual differences. The MRI is also summative, yielding a single quantitative measurement of left–right religious ideology with good scale and test–retest reliability. Analysis of 839 respondents across two studies confirmed the widespread assumption that religious ideology is a parallel construct to political ideology, emerging from similar foundations but following a distinct set of rules. The MRI shows the importance of conceptualizing ideology in ways that access the full spectrum of real-world ideological convictions—an important reminder, given the salience of religious factors for influencing ideology generally. (shrink)

The central project of the Critique of Pure Reason is to answer two sets of questions: What can we know and how can we know it? and What can't we know and why can't we know it? The essays in this collection are intended to help students read the Critique of Pure Reason with a greater understanding of its central themes and arguments, and with some awareness of important lines of criticism of those themes and arguments.

The second edition of The Theory and Practice of Husserl's Phenomenology is a clear and concise introduction to the theoretical background and the rigorous method of Edmund Husserl , perhaps the most influential philosopher of the twentieth century and the founder of the phenomenological movement. According to Husserl phenomenology is not a body of knowledge but a scientific practice based in a rigorous and difficult method, a method that takes long effort and practice to enter into and in which to (...) develop some significant results. Since many scholars and students do not read many of Husserl's published works, this text is meant to show the core unity of focus and method throughout decades of his phenomenological practice and refinement. The present work covers the historical origin of phenomenology and some main thematic results that appear in Husserl's works, and provides an introduction to the "how to" of producing phenomenological description. (shrink)

A general practice research project on ethics is underway at the University of New South Wales, funded by GPEP (General Practice Evaluation Program, Commonwealth Department of Human Services and Health, GPEP 386). Ethical issues, as defined and explored by general practitioners and consumers, are being examined across four areas of Sydney.So far, telephone interviews have been conducted (64% response rate) with a random sample of general practitioners (GPs). Face-to-face interviews have been conducted with 107 consumers, randomly sampled using ABS collection (...) district information. Focus groups have been formed to discuss acceptable solutions to GP and consumer identified ethical issues. This report will report on some preliminary findings to date and will explore professional and consumer roles in the formation of ethical solutions. (shrink)

A general practice research project on ethics is underway at the University of New South Wales, funded by GPEP. Ethical issues, as defined and explored by general practitioners and consumers, are being examined across four areas of Sydney.So far, telephone interviews have been conducted with a random sample of general practitioners. Face-to-face interviews have been conducted with 107 consumers, randomly sampled using ABS collection district information. Focus groups have been formed to discuss acceptable solutions to GP and consumer identified ethical (...) issues. This report will report on some preliminary findings to date and will explore professional and consumer roles in the formation of ethical solutions. (shrink)

The design of medical knowledge-based computer systems requires effective interdisciplinary communication for the development of a community sharing common goals and a common language for design. Over the past 9 years the Perinatal Research Group, an interdisciplinary team of computer scientists, engineers and clinicians, have developed a prototype knowledge-based computer system to aid clinicians in the care of women in labour. The group were uncertain which approach to adopt to progress this system from a prototype to a useful clinical tool (...) to support decision making. A case study and activity theory analysis, of an existing clinical knowledge-based computer system in routine use, helped to resolve a number of communication and methodological issues that the design team encountered. Sharing of backgrounds and perspectives caused the design team to question previous assumptions and to explore alternative functions and roles for knowledge-based computer systems in maternity care. We are now undertaking a longitudinal case study and activity theory analysis of obstetric teams and women in labour to analyse the relationships between clinicians, patients and technology. This work will inform the development of our knowledge-based computer system to place the patient at the centre of the decision-making process. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

Physician-written “do not resuscitate” DNR orders elicit negative reactions from stakeholders that may decrease appropriate end-of-life care. The semantic significance of the phrase has led to a proposed replacement of DNR with “allow natural death” . Prior to this investigation, no scientific papers address the impact of such a change. Our results support this proposition due to increased likelihood of endorsement with the term AND.

Xenophanes and Euripides disapprove of the pan-Hellenic custom of granting athletes conspicuous honors, and Xenophanes in particular, with that of publicly funded meals. Both contrast the uselessness of athletes with the civic contributions of σοφοί. Socrates echoes these sentiments in his counter-proposal that he is much more deserving of σίτησιϚ ἐν πρυτανείῳ than any Olympic athlete. I suggest that Socrates deliberately evokes this topos, but does so with a twist: whereas the earlier passages base their claim to honors on σοφία, (...) Socrates deliberately deprives σοφία of its popular meaning, imbuing it with a much more humble and Delphic connotation, thereby making his proposal all the more outrageous. (shrink)

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend (...) many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N = 20), recent SRC youth (N = 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p = 0.032), decreased functional connectivity between the caudate and each of the pallidum (p = 0.035) and thalamus (p = 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p < 0.038); no changes were observed in recovered asymptomatic youth (N = 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N = 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p = 0.011) and reduced activity in the cerebellum (p = 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p < 0.014), reduced activity of the pallidum (p = 0.002), increased CBF in the caudate (p = 0.005), and reduced diffusivity in the central corpus callosum (p < 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome. (shrink)