CT screening and follow-up of lung nodules: effects of tube current-time setting and nodule size and density on detectability and of tube current-time setting on apparent size

The purpose of the study was to quantify and compare the effect of CT dose and of size and density of nodules on the detectability of lung nodules and to quantify the influence of CT dose on the size of the nodules.

[Lymphadenectomy for bladder cancer: current status and controversies]

Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template.

Disparities in bone density measurement history and osteoporosis medication utilisation in Swiss women: results from the Swiss Health Survey 2007

BACKGROUND Although factors associated with the utilisation of bone density measurement (BDM) and osteoporosis treatment have been regularly assessed in the US and Canada, they have not been effectively analysed in European countries. This study assessed factors associated with the utilisation of BDM and osteoporosis medication (OM) in Switzerland. METHODS The Swiss Health Survey 2007 data included self-reported information on BDM and OM for women aged 40 years and older who were living in private households. Multivariable logistic regression analysis was used to identify sociodemographic, socioeconomic, healthcare-related and osteoporosis risk factors associated with BDM and OM utilisation. RESULTS The lifetime prevalence of BDM was 25.6% (95% CI: 24.3-26.9%) for women aged 40 years and older. BDM utilisation was associated with most sociodemographic factors, all the socioeconomic and healthcare-related factors, and with major osteoporosis risk factors analysed. The prevalence of current OM was 7.8% (95% CI: 7.0-8.6%) and it was associated with some sociodemographic and most healthcare-related factors but only with one socioeconomic factor. CONCLUSIONS In Swiss women, ever having had a BDM and current OM were low and utilisation disparities exist according to sociodemographic, socioeconomic and healthcare-related factors. This might foster further health inequalities. The reasons for these findings should be addressed in further studies of the elderly women, including those living in institutions.

Calculation of crystal optical properties from molecular electron density

We have recently developed a method to obtain distributed atomic polarizabilities adopting a partitioning of the molecular electron density (for example, the Quantum Theory of Atoms in Molecules, [1]), calculated with or without an applied electric field. The procedure [2] allows to obtained atomic polarizability tensors, which are perfectly exportable, because quite representative of an atom in a given functional group. Among the many applications of this idea, the calculation of crystal susceptibility is easily available, either from a rough estimation (the polarizability of the isolated molecule is used) or from a more precise estimation (the polarizability of a molecule embedded in a cluster representing the first coordination sphere is used). Lorentz factor is applied to include the long range effect of packing, which is enhancing the molecular polarizability. Simple properties like linear refractive index or the gyration tensor can be calculated at relatively low costs and with good precision. This approach is particularly useful within the field of crystal engineering of organic/organometallic materials, because it would allow a relatively easy prediction of a property as a function of the packing, thus allowing "reverse crystal engineering". Examples of some amino acid crystals and salts of amino acids [3] will be illustrated, together with other crystallographic or non-crystallographic applications. For example, the induction and dispersion energies of intermolecular interactions could be calculated with superior precision (allowing anisotropic van der Waals interactions). This could allow revision of some commonly misunderstood intermolecular interactions, like the halogen bonding (see for example the recent remarks by Stone or Gilli [4]). Moreover, the chemical reactivity of coordination complexes could be reinvestigated, by coupling the conventional analysis of the electrostatic potential (useful only in the circumstances of hard nucleophilic/electrophilic interaction) with the distributed atomic polarizability. The enhanced reactivity of coordinated organic ligands would be better appreciated. [1] R. F. W. Bader, Atoms in Molecules: A Quantum Theory. Oxford Univ. Press, 1990. [2] A. Krawczuk-Pantula, D. Pérez, K. Stadnicka, P. Macchi, Trans. Amer. Cryst. Ass. 2011, 1-25 [3] A. S. Chimpri1, M. Gryl, L. H.R. Dos Santos1, A. Krawczuk, P. Macchi Crystal Growth & Design, in the press. [4] a) A. J. Stone, J. Am. Chem. Soc. 2013, 135, 7005−7009; b) V. Bertolasi, P. Gilli, G. Gilli Crystal Growth & Design, 2013, 12, 4758-4770.

High-density large-scale field emitter arrays for x-ray free electron laser cathodes

High brightness electron sources are of great importance for the operation of the hard X-ray free electron lasers. Field emission cathodes based on the double-gate metallic field emitter arrays (FEAs) can potentially offer higher brightness than the currently used ones. We report on the successful application of electron beam lithography for fabrication of the large-scale single-gate as well as double-gate FEAs. We demonstrate operational high-density single-gate FEAs with sub-micron pitch and total number of tips up to 106 as well as large-scale double-gate FEAs with large collimation gate apertures. The details of design, fabrication procedure and successful measurements of the emission current from the single- and double-gate cathodes are presented.

Studying functional brain networks with concurrent transcranical alternating current stimulation and EEG

Recently transcranial electric stimulation (tES) has been widely used as a mean to modulate brain activity. The modulatory effects of tES have been studied with the excitability of primary motor cortex. However, tES effects are not limited to the site of stimulation but extended to other brain areas, suggesting a need for the study of functional brain networks. Transcranial alternating current stimulation (tACS) applies sinusoidal current at a specified frequency, presumably modulating brain activity in a frequency-specific manner. At a behavioural level, tACS has been confirmed to modulate behaviour, but its neurophysiological effects are still elusive. In addition, neural oscillations are considered to reflect rhythmic changes in transmission efficacy across brain networks, suggesting that tACS would provide a mean to modulate brain networks. To study neurophysiological effects of tACS, we have been developing a methodological framework by combining transcranial magnetic stimulation (TMS), EEG and tACS. We have developed the optimized concurrent tACS-EEG recording protocol and powerful artefact removal method that allow us to study neurophysiological effects of tACS. We also established the concurrent tACS-TMS-EEG recording to study brain network connectivity while introducing extrinsic oscillatory activity by tACS. We show that tACS modulate brain activity in a phase-dependent manner. Our methodological advancement will open an opportunity to study causal role of oscillatory brain activity in neural transmissions in cortical brain networks.

Solvation-Driven Charge Transfer and Localization in Metal Complexes

In any physicochemical process in liquids, the dynamical response of the solvent to the solutes out of equilibrium plays a crucial role in the rates and products: the solvent molecules react to the changes in volume and electron density of the solutes to minimize the free energy of the solution, thus modulating the activation barriers and stabilizing (or destabilizing) intermediate states. In charge transfer (CT) processes in polar solvents, the response of the solvent always assists the formation of charge separation states by stabilizing the energy of the localized charges. A deep understanding of the solvation mechanisms and time scales is therefore essential for a correct description of any photochemical process in dense phase and for designing molecular devices based on photosensitizers with CT excited states. In the last two decades, with the advent of ultrafast time-resolved spectroscopies, microscopic models describing the relevant case of polar solvation (where both the solvent and the solute molecules have a permanent electric dipole and the mutual interaction is mainly dipole−dipole) have dramatically progressed. Regardless of the details of each model, they all assume that the effect of the electrostatic fields of the solvent molecules on the internal electronic dynamics of the solute are perturbative and that the solvent−solute coupling is mainly an electrostatic interaction between the constant permanent dipoles of the solute and the solvent molecules. This well-established picture has proven to quantitatively rationalize spectroscopic effects of environmental and electric dynamics (time-resolved Stokes shifts, inhomogeneous broadening, etc.). However, recent computational and experimental studies, including ours, have shown that further improvement is required. Indeed, in the last years we investigated several molecular complexes exhibiting photoexcited CT states, and we found that the current description of the formation and stabilization of CT states in an important group of molecules such as transition metal complexes is inaccurate. In particular, we proved that the solvent molecules are not just spectators of intramolecular electron density redistribution but significantly modulate it. Our results solicit further development of quantum mechanics computational methods to treat the solute and (at least) the closest solvent molecules including the nonperturbative treatment of the effects of local electrostatics and direct solvent−solute interactions to describe the dynamical changes of the solute excited states during the solvent response.

Circulating oxidized low-density lipoprotein is associated with echolucent plaques in the femoral artery independently of hsCRP in 61-year-old men.

OBJECTIVES The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.

Materials properties from electron density distributions: Molecular magnetism and linear optical properties

The general goal of this thesis is correlating observable properties of organic and metal-organic materials with their ground-state electron density distribution. In a long-term view, we expect to develop empirical or semi-empirical approaches to predict materials properties from the electron density of their building blocks, thus allowing to rationally engineering molecular materials from their constituent subunits, such as their functional groups. In particular, we have focused on linear optical properties of naturally occurring amino acids and their organic and metal-organic derivatives, and on magnetic properties of metal-organic frameworks. For analysing the optical properties and the magnetic behaviour of the molecular or sub-molecular building blocks in materials, we mostly used the more traditional QTAIM partitioning scheme of the molecular or crystalline electron densities, however, we have also investigated a new approach, namely, X-ray Constrained Extremely Localized Molecular Orbitals (XC-ELMO), that can be used in future to extracted the electron densities of crystal subunits. With the purpose of rationally engineering linear optical materials, we have calculated atomic and functional group polarizabilities of amino acid molecules, their hydrogen-bonded aggregates and their metal-organic frameworks. This has enabled the identification of the most efficient functional groups, able to build-up larger electric susceptibilities in crystals, as well as the quantification of the role played by intermolecular interactions and coordinative bonds on modifying the polarizability of the isolated building blocks. Furthermore, we analysed the dependence of the polarizabilities on the one-electron basis set and the many-electron Hamiltonian. This is useful for selecting the most efficient level of theory to estimate susceptibilities of molecular-based materials. With the purpose of rationally design molecular magnetic materials, we have investigated the electron density distributions and the magnetism of two copper(II) pyrazine nitrate metal-organic polymers. High-resolution X-ray diffraction and DFT calculations were used to characterize the magnetic exchange pathways and to establish relationships between the electron densities and the exchange-coupling constants. Moreover, molecular orbital and spin-density analyses were employed to understand the role of different magnetic exchange mechanisms in determining the bulk magnetic behaviour of these materials. As anticipated, we have finally investigated a modified version of the X-ray constrained wavefunction technique, XC-ELMOs, that is not only a useful tool for determination and analysis of experimental electron densities, but also enables one to derive transferable molecular orbitals strictly localized on atoms, bonds or functional groups. In future, we expect to use XC-ELMOs to predict materials properties of large systems, currently challenging to calculate from first-principles, such as macromolecules or polymers. Here, we point out advantages, needs and pitfalls of the technique. This work fulfils, at least partially, the prerequisites to understand materials properties of organic and metal-organic materials from the perspective of the electron density distribution of their building blocks. Empirical or semi-empirical evaluation of optical or magnetic properties from a preconceived assembling of building blocks could be extremely important for rationally design new materials, a field where accurate but expensive first-principles calculations are generally not used. This research could impact the community in the fields of crystal engineering, supramolecular chemistry and, of course, electron density analysis.

On the Electric Breakdown in Liquid Argon at Centimeter Scale

We present a study on the dependence of electric breakdown discharge properties on electrode geometry and the breakdown field in liquid argon near its boiling point. The measurements were performed with a spherical cathode and a planar anode at distances ranging from 0.1 mm to 10.0 mm. A detailed study of the time evolution of the breakdown volt-ampere characteristics was performed for the first time. It revealed a slow streamer development phase in the discharge. The results of a spectroscopic study of the visible light emission of the breakdowns complement the measurements. The light emission from the initial phase of the discharge is attributed to electro-luminescence of liquid argon following a current of drifting electrons. These results contribute to set benchmarks for breakdown-safe design of ionization detectors, such as Liquid Argon Time Projection Chambers (LAr TPC).