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)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

Psychopaths routinely disregard social norms by engaging in selfish, antisocial, often violent behavior. Commonly characterized as mentally disordered, recent evidence suggests that psychopaths are executing a well-functioning, if unscrupulous strategy that historically increased reproductive success at the expense of others. Natural selection ought to have favored strategies that spared close kin from harm, however, because actions affecting the fitness of genetic relatives contribute to an individual’s inclusive fitness. Conversely, there is evidence that mental disorders can disrupt psychological mechanisms designed to (...) protect relatives. Thus, mental disorder and adaptation accounts of psychopathy generate opposing hypotheses: psychopathy should be associated with an increase in the victimization of kin in the former account but not in the latter. Contrary to the mental disorder hypothesis, we show here in a sample of 289 violent offenders that variation in psychopathy predicts a decrease in the genetic relatedness of victims to offenders; that is, psychopathy predicts an increased likelihood of harming non-relatives. Because nepotistic inhibition in violence may be caused by dispersal or kin discrimination, we examined the effects of psychopathy on (1) the dispersal of offenders and their kin and (2) sexual assault frequency (as a window on kin discrimination). Although psychopathy was negatively associated with coresidence with kin and positively associated with the commission of sexual assault, it remained negatively associated with the genetic relatedness of victims to offenders after removing cases of offenders who had coresided with kin and cases of sexual assault from the analyses. These results stand in contrast to models positing psychopathy as a pathology, and provide support for the hypothesis that psychopathy reflects an evolutionary strategy largely favoring the exploitation of non-relatives. (shrink)

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)

Søren Kierkegaard used his literary, philosophical, and theological voice to reintroduce Christianity to Christendom. In this effort, he repeatedly uses the Apostle Paul's first letter to the church in Corinth. Though some have noted the importance of 1 Corinthians for Kierkegaard, they have not explained this importance nor this letter's role in Kierkegaard's corpus. This essay seeks to fill this gap in Kierkegaard scholarship by explaining the role this letter plays in Kierkegaard's Climacean authorship. Paul's battle with the Corinthian view (...) of wisdom and Kierkegaard's battle with Hegelian philosophy, which seeks to go beyond faith through speculative thinking, share similarities that engender both their works. In their battles with their respective foes, both develop a Christocentric epistemology that displaces the import of human understanding and cognitive content with the person Jesus who inverts their opponents' epistemic values by salvifically redefining wisdom and knowledge. This epistemology of a different kind is an offense, foolishness, and absurd to their opponents because it cannot be intellectually grasped by human understanding, but rather in and through the passion of faith, which places the individual in relation with Jesus. For both authors, this relation is the essential point for the Christian life. (shrink)

LSJ s.v. πρεσβεω II.3.b recorded, on the strength of Thuc. 5.39.2, the meaning ‘go as ambassador’ for the middle voice, in addition to the well-attested ‘send ambassadors’. The passage, however, does not on inspection support the meaning ; it was deleted from the Supplement to LSJ.

LSJ s.v. πρεσβεω II.3.b recorded, on the strength of Thuc. 5.39.2, the meaning ‘go as ambassador’ for the middle voice, in addition to the well-attested ‘send ambassadors’. The passage, however, does not on inspection support the meaning ; it was deleted from the Supplement to LSJ.

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Current views of the control of complex, purposeful movements acknowledge that organizational processes must reconcile multiple concerns. The central priority is of course accomplishing the actor's goal. But in specifying the manner in which this occurs, the action plan must accommodate such factors as the interaction of mechanical forces associated with the motion of a multilinked system (classical mechanics) and, in many cases, intrinsic bias toward preferred movement patterns, characterized by so-called “coordination dynamics.” The most familiar example of the latter (...) is the symmetry constraint, where spatial trajectories and/or temporal landmarks (e.g., reversal points) of concurrentlymoving body segments (limbs, digits, etc.) exhibit mutual attraction. The natural coordination tendencies that emerge through these constraints can facilitate or hinder motor control, depending on the degree of congruency with the desired movement pattern. Motor control theorists have long recognized the role of classical mechanics in theories of movement organization, but an appreciation of the importance of intrinsic interlimb bias has been gained only recently.Although detailed descriptions of temporal coordination dynamics have been provided, systematic attempts to identify additional salient dimensions of interlimb constraint have been lacking. We develop and implement here a novel method for examining this problem by exploiting two robust principles of psychomotor behavior, the symmetry constraint and the Two-Thirds Power Law. Empirical evidence is provided that the relative spatial patterns of concurrently moving limbs are naturally constrained in much the same manner as previously identified temporal constraints and, further, that apparent velocity interference is an indirect, secondary consequence of primary spatial assimilation. The theoretical implications of spatial interference are elaborated with respect to movement organization and motor learning. The need to carefully consider the appropriate dimensions with which to characterize coordination dynamics is also discussed. (shrink)

Bizarre delusions are not specific to schizophrenia and can be found in other psychotic disorders. However, to date, there are no studies investigating socio-demographic and clinical characteristics associated with BizD across the psychosis spectrum. In this study 819 subjects with a diagnosis of SZ, schizoaffective disorder and bipolar I disorder were included. Patients with history of BizD and with no BizD were compared with respect to socidemographic and clinical variables, and predictors of BizD were explored. Patients with BizD were less (...) educated, less likely to be married, had higher Positive and Negative Syndrome Scale negative scores and lower Young Mania Rating Scale scores. Younger age, SZ and SZA diagnoses, higher PANSS positive scores, presence of reference delusions, tactile and olfactory hallucinations were predictors. Our results indicate that BizD are associated with higher illness severity, lower functionality and specific set of symptoms. (shrink)

This volume of the Great American Thinkers series purports to let Thoreau speak for himself, primarily through passages quoted from his journals. Originally published in fourteen volumes, the journals represent over twenty years of Thoreau's life, and are the background and, in some cases, the original form of works more polished and more widely known. Murray has aptly considered Thoreau's wide range of thought and comment under several main headings, such as "Primacy or Purpose," "Society as Burden," and "Freedom and (...) Simplicity." In this arrangement, many of Thoreau's specific and often curt observations can be seen in a more general context, with Thoreau himself providing some of the keys to the transition.--G. B. S. C. (shrink)

Broad, C. D. Leibniz's predicate-in-notion principle and some of its alleged consequences.--Couturat, L. On Leibniz's metaphysics.--Friedrich, C. J. Philosophical reflections of Leibniz on law, politics, and the state.--Curley, E. M. The root of contingency. Furth, M. Monadology.--Hacking, I. Individual substance.--Hintikka, J. Leibniz on plenitude, relations, and the "reign of law."--Ishiguro, H. Leibniz's theory of the ideality of relations.--Kneale, M. Leibniz and Spinoza on activity.--Koyré, A. Leibniz and Newton.--Lovejoy, A. O. Plenitude and sufficient reason in Leibniz and Spinoza.--Mates, B. Leibniz on (...) possible worlds.--Russell, B. Recent work on the philosophy of Leibniz.--Wilson, M. D. On Leibniz's explication of "necessary truth.". (shrink)

Background: Black, Asian and minority ethnic groups have a high need for organ transplantation but deceased donation is low. This restricts the availability of well-matched organs and results in relatively long waiting times for transplantation, with increased mortality risks. Objective: To identify barriers to organ donor registration and family consent among the BAME population, and to develop and evaluate a training intervention to enhance communication with ethnic minority families and identify impacts on family consent. Methods: Three-phase programme comprising community-based research (...) involving two systematic reviews examining attitudes and barriers to organ donation and effective interventions followed by 22 focus groups with minority ethnic groups; hospital-based research examining staff practices and influences on family consent through ethics discussion groups with staff, a study on intensive care units and interviews with bereaved ethnic minority families; and development and evaluation of a training package to enhance cultural competence among ICU staff. Setting: Community focus group study in eight London boroughs with high prevalence of ethnic minority populations. Hospital studies at five NHS hospital trusts. Participants: Community studies: 228 focus group participants; hospital studies: 35 nurses, 28 clinicians, 19 hospital chaplains, 25 members of local Organ Donation Committees, 17 bereaved family members; and evaluation: 66 health professionals. Data sources: Focus groups with community residents, systematic reviews, qualitative interviews and observation in ICUs, EDGs with ICU staff, bereaved family interviews and questionnaires for trial evaluation. Review methods: Systematic review and narrative synthesis. Results: Community studies: Organ Donor Register – different ethnic/faith and age groups were at varying points on the ‘pathway’ to organ donor registration, with large numbers lacking knowledge and remaining at a pre-contemplation stage. Key attitudinal barriers were uncertainties regarding religious permissibility, bodily concerns, lack of trust in health professionals and little priority given to registration, with the varying significance of these factors varying by ethnicity/faith and age. National campaigns focusing on ethnic minorities have had limited impact, whereas characteristics of effective educational interventions are being conducted in a familiar environment; addressing the groups’ particular concerns; delivery by trained members of the lay community; and providing immediate access to registration. Interventions are also required to target those at specific stages of the donation pathway. Hospital studies: family consent to donation – many ICU staff, especially junior nurses, described a lack of confidence in communication and supporting ethnic minority families, often reflecting differences in emotional expression, faith and cultural beliefs, and language difficulties. The continuing high proportion of family donation discussions that take place without the collaboration of a specialist nurse for organ donation reflected consultants’ views of their own role in family consent to donation, a lack of trust in SNODs and uncertainties surrounding controlled donations after circulatory death. Hospital chaplains differed in their involvement in ICUs, reflecting their availability/employment status, personal interests and the practices of ICU staff. Evaluation: professional development package – a digital versatile disk-based training package was developed to promote confidence and skills in cross-cultural communication. Initial evaluation produced positive feedback and significant affirmative attitudinal change but no significant difference in consent rate over the short follow-up period with requirements for longer-term evaluation. Limitations: Participants in the focus group study were mainly first-generation migrants of manual socioeconomic groups. It was not permitted to identify non-consenting families for interview with data regarding the consent process were therefore limited to consenting families. Conclusions: The research presents guidance for the effective targeting of donation campaigns focusing on minority ethnic groups and provides the first training package in cultural competence in the NHS. Future work: Greater evaluation is required of community interventions in the UK to enhance knowledge of effective practice and analysis of the experiences of non-consenting ethnic minority families. Funding: The National Institute for Health Research Programme Grants for Applied Research programme. (shrink)

Health behaviors such as tobacco use contribute significantly to poor health. It is widely recognized that efforts to prevent poor health outcomes should begin in early childhood. Biomedical enhancements, such as a nicotine vaccine, are now emerging and have potential to be used for primary prevention of common diseases. In anticipation of such enhancements, it is important that we begin to consider the ethical and policy appropriateness of their use with children. The main ethical concerns raised by enhancing children relate (...) to their impact on children’s well-being and autonomy. These concerns are significant, however they do not appear to apply in the case of the nicotine vaccine; indeed the vaccine could even further these goals for children. Nevertheless, concerns about broadly applying this enhancement may be more challenging. The vaccine may be less cost-effective than alternative public efforts to prevent tobacco use, utilizing it could distract from addressing the foundational causes of smoking and it might not be publically acceptable. Empirical research about these concerns is needed to ascertain their likelihood and impact as well as how they could be minimized. This research could help determine whether behavior-related enhancements hold promise for improving children’s health. (shrink)

Leibniz's predicate-in-notion principle and some of its alleged consequences, by C. D. Broad.--On Leibniz's metaphysics, by L. Couturat.--Philosophical reflections of Leibniz on law, politics, and the state, by C. J. Friedrich.--The root of contingency, by E. M. Curley.--Monadology, by M. Furth.--Individual substance, by I. Hacking.--Leibniz on plenitude, relations, and the "reign of the law," by J. Hintikka.--Leibniz's theory of the ideality of relations, by H. Ishiguro.--Leibniz and Spinoza on activity, by M. Kneale.--Leibniz and Newton, by A. Koyré.--Plenitude and sufficient reason (...) in Leibniz and Spinoza, by A. O. Lovejoy.--Leibniz on possible worlds, by B. Mates.--Recent work on the philosophy of Leibniz, by B. Russell.--On Leibniz's explication of "necessary truth," by M. D. Wilson.--Bibliography (p. [421]-425). (shrink)