Childhood mental ability and late-onset dementia

In the many epidemiological studies of potential risk factors for dementia, lower mental ability in childhood and in early adult life have been associated with increased risk of dementia. Mechanisms underlying this association are not clear. Of great interest is the emerging evidence linking vascular risk factors to both Alzheimer's disease (AD) and vascular dementia (VaD). Studying life-course cognitive change requires a measure of cognitive ability in early life. The Scottish Mental Survey of 1932 (SMS 1932) gives a valid measure of childhood mental ability age 11 years, the Moray House Test (MHT).1. Relation of MHT to risk of dementia:Cases with vascular dementia had a lower MHT score than controls (mean MHT in cases = 34.0, mean MHT in controls 41.5, p=0.02). This translates to an odds ratio of 0.68 (95% CI 0.50 -0.94; p=0.021) for every 10 point increase in MHT. There was no relationship demonstrated between childhood mental ability and late-onset AD. This association between childhood mental ability and vascular dementia has not been described previously2. Utility of estimation of pre-morbid intelligence in dementia:The estimation of pre-morbid mental ability is often required to demonstrate the cognitive decline required to diagnose dementia. The neuropsychological test most frequently used is the National Adult Reading Test (NART). A question remains about the use of the NART in dementia: some studies have shown NART scores to be lowered in dementia. NART scores were compared in cases with dementia (n=45) to healthy volunteers (n=550). Cases with dementia scored lower on the NART in old age, but also scored lower on MHT age 11. After adjusting the NART score for MHT age 11, the dementia and non-dementia groups no longer differed on NART scores. Pearson correlations between NART and MHT (measured more than 60 years apart) were similar in the dementia group (r = .60) and the non-dementia group (r = .63). These results confirm that the NART is a valid test of pre-morbid mental ability even in the presence of mild-moderate dementia.3. Childhood mental ability and vascular risk:Changes on the resting electrocardiograph (ECG) can be considered a marker of vascular disease. Cognitive test scores were compared in a group of people with and without ECG changes. There was no difference in MHT between the two groups. Men with left ventricular hypertrophy had lower MMSE. Both left ventricular hypertrophy and conduction defects are associated with reduced scores on verbal fluency in women. These results show that even in relatively healthy volunteers, those with markers of vascular disease have lower scores on some tests of cognitive function.Overall, this thesis establishes that lower childhood mental ability is associated with higher risk of dementia. This occurs for vascular but not Alzheimer's dementia. These results are generally supportive of an important vascular contribution to cognitive impairment: lower childhood mental ability is associated with increased cardiovascular risk and hypertension. This is confirmed by a study showing that ECG changes are associated with lower scores on some test of cognition. Additionally, this thesis establishes that a reading test used to estimate pre-morbid mental ability remains valid even in moderate dementia. Future studies are required to examine precise roles of childhood mental ability and risk of dementia particularly the relation of vascular factors to AD and cognitive decline

Enhanced Transmission Due to Disorder

The transmissivity of a one-dimensional random system that is periodic on average is studied. It is shown that the transmission coefficient for frequencies corresponding to a gap in the band structure of the average periodic system increases with increasing disorder while the disorder is weak enough. This property is shown to be universal, independent of the type of fluctuations causing the randomness. In the case of strong disorder the transmission coefficient for frequencies in allowed bands is found to be a non monotonic function of the strength of the disorder. An explanation for the latter behavior is provided.Comment: 9 pages, RevTeX 3.0, 4 Postscript figure

The Creation and Reflection of a Solo Show: Corner of 26 and Lost

We knew coming into this two-year M.F.A. program in June of 2013 that our thesis would culminate in December of 2014 with the performance of a solo show that we would each write and perform ourselves. So as early as out first summer here, we were encouraged to get the ball rolling with potential ideas. The thought this project was to not only give us practice at devising work, but also put a show in our back pocket. So, when we graduated, we would have a full-fledged show that we could take on the road and perform anywhere with little to no support. This project fostered the idea of sending us out of this program not just as better actors, but also as well-rounded artists capable and experienced at creating work for ourselves that could sustain us in a career riddled with uncertainty. This thesis examines the process I underwent from spit balling ideas, to writing, to rehearsing, to performing, and the effect all of this had on me as an actor and an artist

Secoisolariciresinol (SECO) analogues: oxidative metabolism, cytochrome P450 inhibition and implications for toxicity

Secoisolariciresinol (SECO) is the major lignan present in flaxseed, but unlike the structurally related lignan nordihydroguaiaretic acid, it is not associated with toxicity. The major phase I metabolite of SECO is lariciresinol, likely formed as a result of para-quinone methide (p-QM) formation followed by an intramolecular cyclization, thereby minimizing any toxicity associated with the p-QM. Four analogues of SECO were used to investigate substituent effects on lignan metabolism and formation of reactive quinones. HPLC methods were developed for analysis of SECO analogues and their metabolites. The stability of SECO analogues (1 mM) in a 50 mM Na2HPO4 buffer at pH 6.0 and 7.4 were quantified. Enzymatic oxidation experiments using mushroom tyrosinase and microsomes harvested from male Sprague-Dawley rats were performed with and without a GSH trapping system. Mass spectrometry and LC-MS were used to identify metabolites. Life Technologies was contracted to perform IC50 inhibition assays on SECO and the SECO analogues against CYP3A4, CYP3A5, CYP2C9 and CYP2C19 cytochrome P450 isoforms. All SECO analogues were stable at pH 6.0. SECO-2 was stable at pH 7.4 but SECO-1, -3 and -4 were unstable at pH 7.4. Autoxidation of SECO -1, -3 and -4 were 1st order reactions with t1/2 of 9.0 h, 1.7 h and 7.0 h respectively. Mushroom tyrosinase oxidations were performed to generate ortho-quinone standards. SECO-1 -3 and -4 were oxidized by mushroom tyrosinase but SECO-2 was not. Trapping with GSH produces aromatic ring conjugates for SECO-1, -3, -4. Results from microsomal oxidations for SECO-1, -3 and -4 are consistent with these standards. SECO-2 was metabolized by a microsomal system to produce a benzyl GSH adduct. Dealkylation products were also observed. All SECO analogues formed quinones but interestingly, GSH conjugation was competitive with intramolecular cyclization. All cytochrome P450 isoforms were inhibited by every analogue tested to varying degrees, a potential cause of toxicity concerns. Quinones are known to cause toxicity in vivo, including cytotoxicity, immunotoxicity, and carcinogenesis. Our results suggest that since the phenol and catechol lignans form GSH adducts in addition to intramolecular cyclization products, this class of lignans have the potential to cause toxicity

Non-perturbative results for the spectrum of surface-disordered waveguides

We calculated the spectrum of normal scalar waves in a planar waveguide with absolutely soft randomly rough boundaries beyond the perturbation theories in the roughness heights and slopes, basing on the exact boundary scattering potential. The spectrum is proved to be a nearly real non-analytic function of the dispersion $\zeta^2$ of the roughness heights (with square-root singularity) as $\zeta^2 \to 0$. The opposite case of large boundary defects is summarized.Comment: REVTEX 3, OSA style, 9 pages, no figures. Submitted to Optics Letter

Soliton Propagation in Chains with Simple Nonlocal Defects

We study the propagation of solitons on complex chains built by inserting finite graphs at two sites of an unbranched chain. We compare numerical findings with the results of an analytical linear approximation scheme describing the interaction of large-fast solitons with non-local topological defects on a chain. We show that the transmission properties of the solitons strongly depend on the structure of the inserted graph, giving a tool to control the soliton propagation through the choice of pertinent graphs to be attached to the chain.Comment: Published in the special issue of Physica D from a conference on 'Nonlinear Physics: Condensed Matter, Dynamical Systems and Biophysics' held in honour of Serge Aubr

Numerical simulation of electromagnetic wave scattering from planar dielectric films deposited on rough perfectly conducting substrates

Electromagnetic wave scattering from planar dielectric films deposited on one-dimensional, randomly rough, perfectly conducting substrates is studied by numerical simulations for both p- and s-polarization. The reduced Rayleigh equation, which is the integral equation satisfied by the scattering amplitude after eliminating the fields inside the film, is the starting point for the simulation. This equation is solved numerically by considering a random surface of finite length, and by introducing wave number cut-offs in the evanescent part of the spectrum. Upon discretization, a system of linear equations is obtained, and by solving this matrix system for an ensemble of surface realizations, the contribution to the mean differential reflection coefficient from the incoherently scattered field, $<\partial R_\nu/\partial \theta>_{incoh}$ (\nu=p,s), is obtained nonperturbatively. It is demonstrated that when the scattering geometry supports at least two guided waves, $_{incoh}$, has, in addition to the well known enhanced backscattering peak, well-defined satellite peaks in agreement with theory, for most of the parameters considered.Comment: 11 pages and 11 figure

Random Surfaces that Suppress Single Scattering

We present a method for generating numerically a one-dimensional random surface, defined by the equation x_3 = \zx, that suppresses single-scattering processes in the scattering of light from it within a specified range of scattering angles. Rigorous numerical calculations of the scattering of light from surfaces generated by this approach show that the single-scattering contribution to the mean scattered intensity is indeed suppressed within that range of angles.Comment: 3 pagers (Latex), 3 figure