Neuroimaging as a selection tool and endpoint in preclinical and clinical trials

Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a “responder” population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4–6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis

Subleading Shape-Function Effects and the Extraction of |V_ub|

We derive a class of formulae relating moments of B -> Xu l nu to B -> Xs gamma in the shape function region, where m_X^2 ~ m_b Lambda_QCD. We also derive an analogous class of formulae involving the decay B -> Xs l+ l-. These results incorporate Lambda_QCD/m_b power corrections, but are independent of leading and subleading hadronic shape functions. Consequently, they enable one to determine |V_ub|/|V_tb V_ts*| to subleading order in a model-independent way.Comment: 23 page

Toward Full Spatio-Temporal Control on the Nanoscale

We introduce an approach to implement full coherent control on nanometer length scales. It is based on spatio-temporal modulation of the surface plasmon polariton (SPP) fields at the thick edge of a nanowedge. The SPP wavepackets propagating toward the sharp edge of this nanowedge are compressed and adiabatically concentrated at a nanofocus, forming an ultrashort pulse of local fields. The one-dimensional spatial profile and temporal waveform of this pulse are completely coherently controlled.Comment: 4 pages, 3 figures Figures were replace

Lifshitz-like transition and enhancement of correlations in a rotating bosonic ring lattice

We study the effects of rotation on one-dimensional ultra-cold bosons confined to a ring lattice. For commensurate systems, at a critical value of the rotation frequency, an infinitesimal interatomic interaction energy opens a gap in the excitation spectrum, fragments the ground state into a macroscopic superposition of two states with different circulation and generates a sudden change in the topology of the momentum distribution. These features are reminiscent of the topological changes in the Fermi surface that occurs in the Lifshitz transition in fermionic systems. The entangled nature of the ground state induces a strong enhancement of quantum correlations and decreases the threshold for the Mott insulator transition. In contrast to the commensurate case, the incommensurate lattice is rather insensitive to rotation. Our studies demonstrate the utility of noise correlations as a tool for identifying new physics in strongly correlated systems.Comment: 5 pages, 4 figure

Ethics: A Problem in Pharmacy?

Ethics, or the lack or attenuation thereof, is an important issue facing practicing pharmacists today. There are both statutory and regulatory provisions to support the requirement of ongoing education and training in ethics. Evidence of formal disciplinary actions by the California State Board of Pharmacy faced requiring pharmacists to take a formal course in ethics as a condition of retention of licensure is sufficient to demonstrate that pharmacists are deviating from the expectations consistent with ethical behavior. Periodic review of the principles of beneficence, non-malfeasance, autonomy, and justice would benefit pharmacists in practice, as evidence infers that a pharmacist’s moral reasoning erodes with time. Additional training in ethics may be beneficial to the practicing pharmacist, particularly since there is evidence to support that pharmacists with a higher capacity for moral reasoning demonstrated a higher level of clinical performance. Faced with professionals committing ethical breaches compromising their license and the dilemmas created by the commercialization of healthcare, the California State Board of Pharmacy is warranted in their requirement that a portion of the 30 hours of continuing education required for continued licensure be grounded in the training of ethics

A numerical approach for determining the variable ascent velocity of a granitoid diapir

A mathematical model for granitoid diapirism has been developed that accounts for the time dependent thermal and rheological conditions encountered by the intruding body. This model is derived by the simultaneous solution of the partial differential equations of energy, continuity, and momentum utilizing scaling analysis. The underlying assumption is that deformation of the surrounding country rock is confined to a relatively thin layer with a temperature dependent Newtonian viscosity. When the country rock is modeled as a power-law fluid, the effective viscosity is dependent upon temperature and shear strain rate. This model allows for realistic temperature gradients within the crust and variable shear strain rates. This is made possible through use of a numerical approximation referred to as the snapshot approach. This method allows the pluton to ascend in finite time increments while the boundary conditions remain fixed. Following each snapshot, the ascent velocity is calculated and new boundary and initial conditions are set for the next increment of time. Several model runs have been performed using a FORTRAN program. The results exhibit time dependent variations in the ascent velocity due to corresponding changes in the overall rheology, and thickness, of the deformation layer. One of the conclusions from this study is that larger plutons ascend at slower rates, but emplace higher in the crust due to the additional energy available relative to smaller plutons