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The human cerebral white matter (WM) consists of neuronal fibers which are involved in many types of cognitive and motor functions. Macroscopic cerebral WM properties, such as volume or lesion load, can be investigated with conventional magnetic resonance imaging (MRI). Recent developments in diffusion tensor imaging (DTI) now allow for the characterization of the microstructure in cerebral WM, providing us another opportunity to explore WM tissue organization in various clinical diseases. The focus of this thesis is the investigation of brain microstructure with DTI in aging and age-related diseases. The thesis consists of five studies, which are described in Chapters two to six. In addition to the discussion of our findings, future research and critical considerations are introduced in Chapter seven. In Chapter 2, we studied the effect of aging on WM microstructural properties in 145 healthy subjects. Our aim was to identify potential associations between age, gender, and the global and regional fractional anisotropy (FA) and mean diffusivity (MD) using DTI. In total, we studied sixteen regions of interest in both hemispheres to search for regions that display such relationships. In addition, we performed a complementary voxel based analysis, which does not require any a priori hypothesis regarding brain location. A limiting methodological factor of DTI based voxel based analyses, such as the one presented in the second chapter, is the implicit assumption of “linear correlation” when studying brain regions that relate age with a particular diffusion measure of interest. The objective in Chapter 3 was to develop a more sophisticated approach using higher-order polynomial regression models that could overcome this linearity constraint. To demonstrate the benefits of the new statistical framework, we used a large cohort of 346 healthy subjects. After our initial studies of aging and DTI in healthy subjects, we explored the potential contribution of vascular risk factors including aging, hypertension, type 2 diabetes mellitus (T2DM), past history of cardiovascular disease, smoking, and inflammation markers such as homocysteine on the WM microstructure in the following chapters. Our main aim in Chapter 4 was to examine potential differences in brain organization in terms of diffusion measures between 40 T2DM patients without cognitive complaints and 97 healthy controls. Despite previously observed associations between the vascular risk factor homocysteine and macroscopic structural brain changes, it is still unknown whether microstructural associations with brain tissue properties can be observed using clinical routine MRI. The aim of the study presented in Chapter 5 was to investigate such potential relationships between homocysteine levels and microstructural measures in 338 healthy participants, while controlling for several other vascular risk factors. In addition, we studied how the age-related white matter changes (ARWMC) score and the Framingham Stroke Risk Profile (FSRP) were related to these DTI metrics. Our main aims in Chapter 6 were to investigate the WM microstructure in patients with vascular parkinsonism (VP) using DTI and to examine specific fiber tract involvement with respect to clinical severity. We performed global, voxel-based, and tract-based analyses to compare WM microstructural properties between the two groups

Polypharmacy and medication use by cancer history in a nationally representative group of adults in the USA, 2003–2014

Purpose: This study examines polypharmacy and prescription drug use patterns in cancer survivors, a growing population at risk for cancer sequelae and side effects from treatment, which can arise months or even years following diagnosis. Survivors may experience greater medication burden than the general population, increasing concerns for polypharmacy and subsequent risks of drug interactions and non-adherence. Methods: Using the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2014, we examined the association between a cancer history and presence of polypharmacy (5+ medications). We estimated prevalence ratios and prevalence differences for polypharmacy comparing those with and without a cancer history using binomial regression models and propensity score (PS) weighting to account for baseline differences between groups. Results: We identified 32,238 adults aged 20 years or older; 1899 had cancer (excluding non-melanoma skin) at least 1 year before the survey. Overall, polypharmacy prevalence was 13% and 35% in those with and without a cancer history, respectively. After PS weighting, the polypharmacy prevalence was 1.26 times higher among those with versus without a cancer history (weighted prevalence ratio, 1.26; 95% CI, 1.18, 1.35). In sub-group analyses, the weighted prevalence ratio was largest for those 20–39 years old at survey (2.78; 95% CI, 1.71, 4.53), and the weighted prevalence difference was largest for those 40–64 years old at survey (9.35%; 95% CI, 5.70%, 13.01%). Conclusions/Implications for Cancer Survivors: Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management

Observation of Magnetic Moments in the Superconducting State of YBa2_2Cu3_3O6.6_{6.6}

Neutron Scattering measurements for YBa$_2$Cu$_3$O$_{6.6}$ have identified small magnetic moments that increase in strength as the temperature is reduced below $T^\ast$ and further increase below $T_c$. An analysis of the data shows the moments are antiferromagnetic between the Cu-O planes with a correlation length of longer than 195 \AA in the $a$-$b$ plane and about 35 \AA along the c-axis. The origin of the moments is unknown, and their properties are discusssed both in terms of Cu spin magnetism and orbital bond currents.Comment: 9 pages, and 4 figure

Illuminating interfaces between phases of a U(1) x U(1) gauge theory

We study reflection and transmission of light at the interface between different phases of a U(1) x U(1) gauge theory. On each side of the interface, one can choose a basis so that one generator is free (allowing propagation of light), and the orthogonal one may be free, Higgsed, or confined. However, the basis on one side will in general be rotated relative to the basis on the other by some angle alpha. We calculate reflection and transmission coefficients for both polarizations of light and all 8 types of boundary, for arbitrary alpha. We find that an observer measuring the behavior of light beams at the boundary would be able to distinguish 4 different types of boundary, and we show how the remaining ambiguity arises from the principle of complementarity (indistinguishability of confined and Higgs phases) which leaves observables invariant under a global electric/magnetic duality transformation. We also explain the seemingly paradoxical behavior of Higgs/Higgs and confined/confined boundaries, and clarify some previous arguments that confinement must involve magnetic monopole condensation.Comment: RevTeX, 12 page

Effective flexural stiffness of slender reinforced concrete columns under axial forces and biaxial bending

Most of the design codes (ACI-318-2008 and Euro Code-2-2004) propose the moment magnifier method in order to take into account the second order effect to design slender reinforced concrete columns. The accuracy of this method depends on the effective flexural stiffness of the column. This paper proposes a new equation to obtain the effective stiffness EI of slender reinforced concrete columns. The expression is valid for any shape of cross-section, subjected to combined axial loads and biaxial bending, both for short-time and sustained loads, normal and high strength concretes, but it is only suitable for columns with equal effective buckling lengths in the two principal bending planes. The new equation extends the proposed EI equation in the "Biaxial bending moment magnifier method" by Bonet et al. (2004) [6], which is valid only for rectangular sections. The method was compared with 613 experimental tests from the literature and a good degree of accuracy was obtained. It was also compared with the design codes ACI-318 (08) and EC-2 (2004) improving the precision. The method is capable to verify and design with sufficient accuracy slender reinforced concrete columns in practical engineering design applications. © 2010 Elsevier Ltd.The authors wish to express their sincere gratitude to the Spanish "Ministerio de Ciencia e Innovacion" for help provided through projects BIA2008-03734 and BIA2009-10207 and to the European Community with the Feder funds.Bonet Senach, JL.; Romero, ML.; Miguel Sosa, P. (2011). Effective flexural stiffness of slender reinforced concrete columns under axial forces and biaxial bending. Engineering Structures. 33:881-893. doi:10.1016/j.engstruct.2010.12.009S8818933

Staggered Currents in the Vortex Core

We study the electronic structure of the vortex core in the cuprates using the U(1) slave-boson mean-field wavefunctions and their Gutzwiller projection. We conclude that there exists local orbital antiferromagnetic order in the core near optimal doping. We compare the results with that of BCS theory and analyze the spatial dependence of the local tunneling density of states.Comment: 4 pages, 3 figure

Association between concomitant use of hydrochlorothiazide and adverse chemotherapy-related events among older women with breast cancer treated with cyclophosphamide

Background: The pharmacy reference database, Micromedex, lists concomitant hydrochlorothiazide and cyclophosphamide use as a potential, major drug-drug interaction (DDI), although only one small, single-center study supports this claim. Our objective was to estimate associations between this potential DDI and two adverse chemotherapy-related events, neutropenia-related hospitalizations and treatment regimen discontinuation, among a cohort of women with breast cancer initiating adjuvant chemotherapy containing cyclophosphamide. Methods: Using linked Surveillance, Epidemiology, and End Results Program (SEER)-Medicare data, we included women 66 years and older with breast cancer diagnosis between 2007 and 2011, who initiated a regimen containing cyclophosphamide. Risk ratios (RR) and 95% confidence intervals for adverse outcomes comparing women exposed versus unexposed to the potential DDI were assessed using modified multivariable Poisson regression adjusting for potential confounders. Results: In total, 27% of women receiving cyclophosphamide treatment were exposed to concomitant hydrochlorothiazide, of which 11% experienced a neutropenia-related hospitalization and 21% discontinued their chemotherapy regimen prior to completion. Adjusted risks of both adverse events were similar between those exposed and unexposed to the potential DDI [neutropenia-related hospitalization: adjusted RR (aRR) = 0.92 (0.70-1.21); treatment discontinuation: aRR = 1.00 (0.96-1.05)]. Conclusions: Our results do not support an association between concomitant hydrochlorothiazide use and two clinically relevant adverse chemotherapy-related events. Impact: Our results support reassessing and potentially lowering severity of this potential interaction in drug reference databases

Reformulating Supersymmetry with a Generalized Dolbeault Operator

The conditions for N=1 supersymmetry in type II supergravity have been previously reformulated in terms of generalized complex geometry. We improve that reformulation so as to completely eliminate the remaining explicit dependence on the metric. Doing so involves a natural generalization of the Dolbeault operator. As an application, we present some general arguments about supersymmetric moduli. In particular, a subset of them are then classified by a certain cohomology. We also argue that the Dolbeault reformulation should make it easier to find existence theorems for the N=1 equations.Comment: 30 pages, no figures. v2: minor correction