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

Effect of Phosphorus Nutrition on Growth and Physiology of Cotton Under Ambient and Elevated Carbon Dioxide

Phosphorous deficiency in soil limits crop growth and productivity in the majority of arable lands worldwide and may moderate the growth enhancement effect of rising atmospheric carbon dioxide (CO2) concentration. To evaluate the interactive effect of these two factors on cotton (Gossypium hirsutum) growth and physiology, plants were grown in controlled environment growth chambers with three levels of phosphate (Pi) supply (0.20, 0.05 and 0.01 mM) under ambient and elevated (400 and 800 μmol mol‒1, respectively) CO2. Phosphate stress caused stunted growth and resulted in early leaf senescence with severely decreased leaf area and photosynthesis. Phosphate stress led to over 77 % reduction in total biomass across CO2 levels. There was a below-ground (roots) shift in biomass partitioning under Pi deficiency. While tissue phosphorus (P) decreased, tissue nitrogen (N) content tended to increase under Pi deficiency. The CO2 × Pi interactions were significant on leaf area, photosynthesis and biomass accumulation. The stimulatory effect of elevated CO2 on growth and photosynthesis was reduced or highly depressed suggesting an increased sensitivity of cotton to Pi deficiency under elevated CO2. Although, tissue P and stomatal conductance were lower at elevated CO2, these did not appear to be the main causes of cotton unresponsiveness to elevated CO2 under severe Pi-stress. The alteration in the uptake and utilization of N was suggested due to a consistent reduction (18–21 %) in the cotton plant tissue N content under elevated CO2

Critical role for BIM in T cell receptor restimulation-induced death

<p>Abstract</p> <p>Background</p> <p>Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR)-triggered propriocidal cell death important for governing the intensity of immune responses. This is thought to be chiefly mediated by an extrinsic signal through the Fas-FasL pathway. However, we observed that TCR restimulation still potently induced apoptosis when this interaction was blocked, or genetically impaired in T cells derived from autoimmune lymphoproliferative syndrome (ALPS) patients, prompting us to examine Fas-independent, intrinsic signals.</p> <p>Results</p> <p>Upon TCR restimulation, we specifically noted a marked increase in the expression of BIM, a pro-apoptotic Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression is suppressed were more resistant to restimulation-induced death. Strikingly, knockdown of BIM expression rescued normal T cells from TCR-induced death to as great an extent as Fas disruption.</p> <p>Conclusion</p> <p>Our data implicates BIM as a critical mediator of apoptosis induced by restimulation as well as growth cytokine withdrawal. These findings suggest an important role for BIM in eliminating activated T cells even when IL-2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Wendy Davidson (nominated by Dr. David Scott), Dr. Mark Williams (nominated by Dr. Neil Greenspan), and Dr. Laurence C. Eisenlohr.</p

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

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

"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

Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting and other symptoms, separated by intervals of comparative wellness. This report describes the clinical features, co-morbidities and problems encountered in management of 41 adult patients who met the diagnostic criteria for CVS. METHODS: This is a retrospective study of adults with CVS seen between 1994 and 2003. Follow-up data were obtained by mailed questionnaires. RESULTS: Age of onset ranged from 2 to 49 years. The duration of CVS at the time of consultation ranged from less than 1 year to 49 years. CVS episodes were stereotypic in respect of their hours of onset, symptomatology and length. Ninety-three percent of patients had recognizable prodromes. Half of the patients experienced a constellation of symptoms consisting of CVS episodes, migraine diathesis, inter-episodic dyspeptic nausea and a history of panic attacks. Deterioration in the course of CVS is indicated by coalescence of episodes in time. The prognosis of CVS is favorable in the majority of patients. CONCLUSION: CVS is a disabling disorder affecting adults as well as children. Because its occurrence in adults is little known, patients experience delayed or mis-diagnosis and ineffectual, sometimes inappropriately invasive management

The CP violating asymmetry in B±→MMˉπ±B^{\pm} \to M {\bar M} \pi^{\pm} decays

We analyze the asymmetry in the partial widths for the decays $B^{\pm} \to M {\bar M} \pi^{\pm}$ ($M = \pi^+, K ^+, \pi^0, \eta$), which results from the interference of the nonresonant decay amplitude with the resonant amplitude for $B^{\pm} \to \chi_{c0} \pi^{\pm}$ followed by the decay $\chi_{c0} \to M {\bar M}$. The CP violating phase $\gamma$ can be extracted from the measured asymmetry. We find that the partial width asymmetry for $B^\pm \to \pi^+ \pi^- \pi^\pm$ is about $0.33~sin \gamma$, and about $0.45~ sin \gamma$ for $B^\pm \to K^+ K^-\pi^\pm$, while it is somewhat smaller for $B^\pm \to \pi^0 \pi^0 \pi^\pm$ and $B^\pm \to \eta \eta \pi^\pm$. Potential sources of uncertainties in these results, primarily coming from poorly known input parameters, are discussed.Comment: 12 pages, latex, 1 figure, submitted to Phis. Lett.

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