Testing of a Market Fraction Model and Power-law Behaviour in the DAX 30

This paper tests a simple market fraction asset pricing model with heterogeneous
agents. By selecting a set of structural parameters of the model through a systematic procedure, we show that the autocorrelations (of returns, absolute returns and squared returns) of the market fraction model share the same pattern as those of the DAX 30. By conducting econometric analysis via Monte Carlo simulations, we characterize these power-law behaviours and find that estimates of the power-law decay indices, the (FI)GARCH parameters, and the tail index of the selected market fraction model closely match those of the DAX 30. The results strongly support the explanatory power of the heterogeneous agent models.

The use of water soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle invasive bladder cancer

Objectives: To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods: Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings: Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion: The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO₂^–) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2vs. 6.6 ± 0.3 m s⁻¹; P = 0.001). These changes persisted at days 12–14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO₂^– increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r = −0.53) and chronic (n = 7, r = −0.69; P ≤ 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspired O₂ fraction () = 0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α₁-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling.

Predictive Factors for Local Control in Primary and Metastatic Lung Tumours after Four to Five Fraction Stereotactic Ablative Body Radiotherapy: A Single Institution's Comprehensive Experience

AIMS: We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control.

MATERIALS AND METHODS: In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses.

RESULTS: Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control.

CONCLUSIONS: Lung SABR of 48-60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.

Process for the preparation of water-soluble cellulose hydrolysis products.

The title process comprises admixing cellulose with an ionic liq. capable of solvating or dissolving at least some of the cellulose, the ionic liq. being a compd. comprised solely of cations and anions (e.g., 1-ethyl-3-methylimidazolium sulfate) and which exists in a liq. state at a temp. at or below 150°, and in which the anions are selected from sulfate, hydrogen sulfate and nitrate; and treating the resulting solvate or soln. with an acid in the presence of water, the acid having a pKa in water of less than 2 at 25°. [on SciFinder(R)]

Process for the preparation of water-soluble cellulose hydrolysis products.

The title process comprises admixing cellulose with an ionic liq. capable of solvating or dissolving at least some of the cellulose, the ionic liq. being a compd. comprised solely of cations and anions (e.g., 1-ethyl-3-methylimidazolium sulfate) and which exists in a liq. state at a temp. at or below 150°, the cations in the ionic liq. having the general formula R1Z(R2)(R3)R4: in which Z represents a nitrogen or phosphorus atom, R1 represents a Me or Et group, each of R2 and R3, which may be the same or different, is selected from C4-8alkyl, optionally-substituted benzyl, optionally-substituted Ph, and C5-7cycloalkyl, and R4 represents C1-8 alkyl, optionally-substituted benzyl, optionally-substituted Ph or C5-7cyclohexyl; in which the optional substituents on a benzyl or Ph ring are one, two or three substituents selected from C1-4alkyl or alkoxy groups, halogen atoms and nitro groups; and treating the resulting solvate or soln. with an acid in the presence of water, the acid having a pKa in water of less than 2 at 25°. [on SciFinder(R)]

Drug Polymer Thermodynamic Phase Diagrams in the Selection of Optimal API-Polymer Compositions for Amorphous Solid Dispersions

Purpose The aim of this work was to examine, for amorphous solid dispersions, how the thermal analysis method selected impacts on the construction of thermodynamic phase diagrams, and to assess the predictive value of such phase diagrams in the selection of optimal, physically stable API-polymer compositions. Methods Thermodynamic phase diagrams for two API/polymer systems (naproxen/HPMC AS LF and naproxen/Kollidon 17 PF) were constructed from data collected using two different thermal analysis methods. The “dynamic” method involved heating the physical mixture at a rate of 1 &[deg]C/minute. In the "static" approach, samples were held at a temperature above the polymer Tg for prolonged periods, prior to scanning at 10 &[deg]C/minute. Subsequent to construction of phase diagrams, solid dispersions consisting of API-polymer compositions representative of different zones in the phase diagrams were spray dried and characterised using DSC, pXRD, TGA, FTIR, DVS and SEM. The stability of these systems was investigated under the following conditions: 25 &[deg]C, desiccated; 25 &[deg]C, 60 % RH; 40 &[deg]C, desiccated; 40 &[deg]C, 60 % RH. Results Endset depression occurred with increasing polymer volume fraction (Figure 1a). In conjunction with this data, Flory-Huggins and Gordon-Taylor theory were applied to construct thermodynamic phase diagrams (Figure 1b). The Flory-Huggins interaction parameter (&[chi]) for naproxen and HPMC AS LF was + 0.80 and + 0.72, for the dynamic and static methods respectively. For naproxen and Kollidon 17 PF, the dynamic data resulted in an interaction parameter of - 1.1 and the isothermal data produced a value of - 2.2. For both systems, the API appeared to be less soluble in the polymer when the dynamic approach was used. Stability studies of spray dried solid dispersions could be used as a means of validating the thermodynamic phase diagrams. Conclusion The thermal analysis method used to collate data has a deterministic effect on the phase diagram produced. This effect should be considered when constructing thermodynamic phase diagrams, as they can be a useful tool in predicting the stability of amorphous solid dispersions.

The Use of High Surface Area Silica and Supercritical Carbon Dioxide to Enhance Solubility of Poorly Water-Soluble Drugs

Purpose Poor water-solubility of BCS class II drugs can limit their commercialization because of reduced oral bioavailability. It has been reported that loading of drug by adsorption onto porous silica would enhance drug solubility due to the increased surface area available for solvent diffusion. In this work, solid dispersions are formed using supercritical carbon dioxide (scCO2). The aim of this research was to characterise the solid-state properties of scCO2 dispersion and to investigate the impact of altering scCO2 processing conditions on final amorphous product performance that could lead to enhancement of drug dissolution rate for BCS class II drugs. Methods Indomethacin (IND) was purchased from Sigma-Aldrich (Dorset, UK) and was used as a model drug with two grades of high surface area silica (average particle sizes 3&[micro] and 7&[micro]), which were obtained directly from Grace-Davison (Germany). Material crystallinity was evaluated using powder X-ray diffraction (PXRD, Rigaku™, miniflex II, Japan) and high-speed differential scanning calorimetry (Hyper-DSC 8000, Perkin Elmer, USA). Materials were placed in a high-pressure vessel consisting of a CO2 cylinder, a Thar™ Technologies P50 high-pressure pump and a 750 ml high-pressure vessel (Thar, USA). Physical mixtures were exposed to CO2 gas above its critical conditions. SEM imaging and elemental analysis were conducted using a Jeol 6500 FEGSEM (Advanced MicroBeam Inc., Austria). Drug release was examined using USP type II dissolution tester (Caleva™, UK). Results The two grades of silica were found to be amorphous using PXRD and Hyper-DSC. Using PXRD, it was shown that an increase in incubation time and pressure resulted in a decrease in the crystalline content. Drug release profiles from the two different silica formulations prepared under the same conditions are shown in Figure 1. It was found that there was a significant enhancement in drug release, which was influenced, by silica type and other experiment conditions such as temperature, pressure and exposure time. SEM imaging and elemental analysis showed drug deposited inside silica pores as well as on the outer surface. Conclusion This project has shown that silica carrier platforms may be used as an alternative approach to generating polymeric solid dispersions of amorphous drugs exhibiting enhanced solubility.

Formation of soluble mercury oxide coatings: transformation of elemental mercury in soils

The impact of mercury (Hg) on human and ecological health has been known for decades. Although a treaty signed in 2013 by 147 nations regulates future large-scale mercury emissions, legacy Hg contamination exists worldwide and small scale releases will continue. The fate of elemental mercury, Hg(0), lost to the subsurface and its potential chemical transformation that can lead to changes in speciation and mobility are poorly understood. Here we show that Hg(0) beads interact with soil or manganese oxide solids and x-ray spectroscopic analysis indicates that the soluble mercury coatings are HgO. Dissolution studies show that after reacting with a composite soil, > 20 times more Hg is released into water from the coated beads than from a pure liquid mercury bead. An even larger, > 700 times, release occurs from coated Hg(0) beads that have been reacted with manganese oxide, suggesting that manganese oxides are involved in the transformation of the Hg(0) beads and creation of the soluble mercury coatings. Although the coatings may inhibit Hg(0) evaporation, the high solubility of the coatings can enhance Hg(II) migration away from the Hg(0)-spill site and result in potential changes in mercury speciation in the soil and increased mercury mobility.

The white dwarf's carbon fraction as a secondary parameter of Type Ia supernovae

Context. Binary stellar evolution calculations predict thatChandrasekhar-mass carbon/oxygen white dwarfs (WDs) show a radiallyvarying profile for the composition with a carbon depleted core. Manyrecent multi-dimensional simulations of Type Ia supernovae (SNe Ia),however, assume the progenitor WD has a homogeneous chemicalcomposition.
Aims: In this work, we explore the impact ofdifferent initial carbon profiles of the progenitor WD on the explosionphase and on synthetic observables in the Chandrasekhar-mass delayeddetonation model. Spectra and light curves are compared to observationsto judge the validity of the model.
Methods: The explosion phaseis simulated using the finite volume supernova code Leafs, which isextended to treat different compositions of the progenitor WD. Thesynthetic observables are computed with the Monte Carlo radiativetransfer code Artis. Results: Differences in binding energies ofcarbon and oxygen lead to a lower nuclear energy release for carbondepleted material; thus, the burning fronts that develop are weaker andthe total nuclear energy release is smaller. For otherwise identicalconditions, carbon depleted models produce less 56Ni.Comparing different models with similar 56Ni yields showslower kinetic energies in the ejecta for carbon depleted models, butonly small differences in velocity distributions and line velocities inspectra. The light curve width-luminosity relation (WLR) obtained formodels with differing carbon depletion is roughly perpendicular to theobserved WLR, hence the carbon mass fraction is probably only asecondary parameter in the family of SNe Ia.
Tables 3 and 4 are available in electronic form at http://www.aanda.org