Applications of neuroimaging to disease-modification trials in Alzheimer's disease.

Critical to development of new therapies for Alzheimer's disease (AD) is the ability to detect clinical or pathological change over time. Clinical outcome measures typically used in therapeutic trials have unfortunately proven to be relatively variable and somewhat insensitive to change in this slowly progressive disease. For this reason, development of surrogate biomarkers that identify significant disease-associated brain changes are necessary to expedite treatment development in AD. Since AD pathology is present in the brain many years prior to clinical manifestation, ideally we want to develop biomarkers of disease that identify abnormal brain structure or function even prior to cognitive decline. Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new amyloid imaging techniques, and spinal fluid markers of AD all have great potential to provide surrogate endpoint measures for AD pathology. The Alzheimer's disease neuroimaging initiative (ADNI) was developed for the distinct purpose of evaluating surrogate biomarkers for drug development in AD. Recent evidence from ADNI demonstrates that imaging may provide more sensitive, and earlier, measures of disease progression than traditional clinical measures for powering clinical drug trials in Alzheimer's disease. This review discusses recently presented data from the ADNI dataset, and the importance of imaging in the future of drug development in AD

Covariant equations for the three-body bound state

The covariant spectator (or Gross) equations for the bound state of three identical spin 1/2 particles, in which two of the three interacting particles are always on shell, are developed and reduced to a form suitable for numerical solution. The equations are first written in operator form and compared to the Bethe-Salpeter equation, then expanded into plane wave momentum states, and finally expanded into partial waves using the three-body helicity formalism first introduced by Wick. In order to solve the equations, the two-body scattering amplitudes must be boosted from the overall three-body rest frame to their individual two-body rest frames, and all effects which arise from these boosts, including the Wigner rotations and rho-spin decomposition of the off-shell particle, are treated exactly. In their final form, the equations reduce to a coupled set of Faddeev-like double integral equations with additional channels arising from the negative rho-spin states of the off-shell particle.Comment: 57 pages, RevTeX, 6 figures, uses epsf.st

What’s Sex (Composition) Got to Do with It? The Importance of Sex Composition of Gangs for Female and Male Members’ Offending and Victimization

Sex composition of groups has been theorized in organizational sociology and found in prior work to structure female and male members’ behaviors and experiences. Peer group and gang literature similarly finds that the sex gap in offending varies across groups of differing sex ratios. Drawing on this and other research linking gang membership, offending, and victimization, we examine whether sex composition of gangs is linked to sex differences in offending in this sample, further assess whether sex composition similarly structures females’ and males’ victimization experiences, and if so, why. Self-report data from gang members in a multi-site, longitudinal study of 3,820 youths are employed. Results support previous findings about variations in member delinquency by both sex and sex composition of the gang and also indicate parallel variations in members’ victimization. These results are further considered within the context of facilitating effects such as gender dynamics, gang characteristics, and normative orientation

Spin relaxation in low-dimensional systems

We review some of the newest findings on the spin dynamics of carriers and excitons in GaAs/GaAlAs quantum wells. In intrinsic wells, where the optical properties are dominated by excitonic effects, we show that exciton-exciton interaction produces a breaking of the spin degeneracy in two-dimensional semiconductors. In doped wells, the two spin components of an optically created two-dimensional electron gas are well described by Fermi-Dirac distributions with a common temperature but different chemical potentials. The rate of the spin depolarization of the electron gas is found to be independent of the mean electron kinetic energy but accelerated by thermal spreading of the carriers.Comment: 1 PDF file, 13 eps figures, Proceedings of the 1998 International Workshop on Nanophysics and Electronics (NPE-98)- Lecce (Italy

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

"It’s sort of reaffirmed to me that I'm not a monster, I'm not a terrible person": sex offenders’ movements toward desistance via peer-support roles in prison

Individuals incarcerated in prisons across the United Kingdom and abroad are able to volunteer for a variety of peer-support roles, which are characterized by prisoner-to-prisoner helping. Some research has found that such roles can represent turning points in the lives of those who have offended and encourage movements toward desistance. This proposed redemptive influence is argued to result from the prosocial behaviors that such roles appear to elicit in their holders. The present study aims to explore the mechanics of this claimed influence. While a limited amount of research has attempted this on a general offending population, no research has done so with a sample of sexual offenders. Given the intensive treatment programs involved in such contexts, and the requirements for sexual offenders to demonstrate reduced risk, the authors believe those serving time for sexual offenses represent an important sample on which to explore the potentially redemptive properties of peer-support roles. To this end, 13 peer supporters participated in semistructured interviews. Transcripts were analyzed using a phenomenologically oriented thematic analysis. Results suggest that sexual offenders who adopt peer-support roles are able to live up to desired selves by “doing good” in prison, “giving back,” and consequently resisting negative labels. These benefits have been theoretically linked with better reintegration outcomes for sexual offenders, who are publicly denigrated in the extreme and find it especially difficult to (re)integrate. Suggestions regarding the future utility of such schemes are offered

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

The Impossibility of a Perfectly Competitive Labor Market

Using the institutional theory of transaction cost, I demonstrate that the assumptions of the competitive labor market model are internally contradictory and lead to the conclusion that on purely theoretical grounds a perfectly competitive labor market is a logical impossibility. By extension, the familiar diagram of wage determination by supply and demand is also a logical impossibility and the neoclassical labor demand curve is not a well-defined construct. The reason is that the perfectly competitive market model presumes zero transaction cost and with zero transaction cost all labor is hired as independent contractors, implying multi-person firms, the employment relationship, and labor market disappear. With positive transaction cost, on the other hand, employment contracts are incomplete and the labor supply curve to the firm is upward sloping, again causing the labor demand curve to be ill-defined. As a result, theory suggests that wage rates are always and everywhere an amalgam of an administered and bargained price. Working Paper 06-0

“I Think I Became a Swimmer Rather than Just Someone with a Disability Swimming Up and Down”: Paralympic Athletes Perceptions of Self and Identity Development

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Disability and Rehabilitation on 27 September 2016, available online at:DOI: https://doi.org/10.1080/09638288.2016.1217074.Purpose: The purpose of this study was to explore the role of swimming on Paralympic athletes’ perceptions of self and identity development. Method: A hermeneutic phenomenological approach was taken. During semi-structured interviews five Paralympic swimmers (aged 20-24 years) were asked questions about their swimming career, perceptions of self, integration, and impairment. Interviews were audio-recorded and transcribed verbatim. Results: An Interpretative Phenomenological Analysis1 yielded three superordinate themes: a) ‘One of the crowd’; none of the participants viewed themselves as disabled, nor as supercrips; these perceptions stemmed from family-, school-, and swimming- related experiences, b) ‘Becoming me’; participation in swimming facilitated self- and social-acceptance, and identity development, and c) ‘A badge of honour’; swimming presented opportunity to present and reinforce a positive identity. Conclusions: Swimming experiences enabled the participants to enhance personal and social identities, integrate through pro-social mechanisms, and to develop a career path following retirement from competition.through pro-social mechanisms, and to develop a career path following retirement from competition.Peer reviewe