Doxorubicin eluting beads − 1: Effects of drug loading on bead characteristics and drug distribution

DC Bead^TM is a FDA cleared embolisation device for the treatment of hypervascular tumours and arteriovenous malformations. This product is currently evaluated in a number of centres in Europe as an embolic device for transarterial chemoembolisation (TACE). The beads consist of poly(vinyl alcohol) microspheres modified with sulfonic acid groups and are available at different size ranges varying from 100 to 900 μm in diameter. The beads were shown to actively sequester doxorubicin hydrochloride (dox) from solution in a time dependent upon the dose of the drug and size of the beads. Drug uptake was by an ion-exchange mechanism, and in the absence of other ions in solution, the beads could load a maximum of around 40 mg dox/mL hydrated beads, with >99% of drug being sequestered from the solution. A loading of 25 mg dox/mL beads was recommended as providing a practical therapeutic dose and optimum handling characteristics. There was a decrease in equilibrium water content of the beads with increasing dox loading, which resulted in a decrease in the average diameter of the beads and an increase in the compressive modulus. The deliverability properties, however, were not affected after drug loading. Using a variety of microscopic methods, the drug was shown to be distributed throughout the bead structure, but concentrated in the outer 20 μm surface layer, a feature related to the method of synthesis. This study characterises the properties of DC Bead loaded with dox with respect to important characteristics in embolisation and demonstrates the potential of this drug device combination for the treatment of hypervascular tumours such as hepatocellular carcinoma.     

Theoretical quality assessment of myocardial elastography with in vivo validation

Myocardial elastography (ME), a radio frequency (RF)-based speckle tracking technique with one-dimensional (1-D) cross correlation and novel recorrelation methods in a 2-D search was proposed to estimate and fully image 2-D transmural deformation field and to detect abnormal cardiac function. A theoretical framework was first developed in order to evaluate the performance of 2-D myocardial elastography based on a previously developed 3-D finite-element model of the canine left ventricle. A normal (control) and an ischemic (left-circumflex, LCx) model, which more completely represented myocardial deformation than a kinematic model, were considered. A 2-D convolutional image formation model was first used to generate RF signals for quality assessment of ME in the normal and ischemic cases. A 3-D image formation model was further developed to investigate the effect of the out-of-plane motion on the 2-D, in-plane motion estimation. Both orthogonal, in-plane displacement components (i.e., lateral and axial) between consecutive RF frames were iteratively estimated. All the estimated incremental 2-D displacements from end-diastole (ED) to end-systole (ES) were then accumulated to acquire the cumulative 2-D displacements, which were further used to calculate the cumulative 2-D systolic finite strains. Furthermore, the cumulative systolic radial and circumferential strains, which were angle- and frame-rate independent, were obtained from the 2-D finite-strain components and imaged in full view to detect the ischemic region. We also explored the theoretical understanding of the limitations of our technique for the accurate depiction of disease and validated it in vivo against tagged magnetic resonance imaging (tMRI) in the case of a normal human myocardium in a 2-D short-axis (SA) echocardiographic view. The theoretical framework succeeded in demonstrating that the 2-D myocardial elastography technique was a reliable tool for the complete estimation and depiction of the in-plane myocardial deformation field as well as for accurate identification of pathological mechanical function using established finite-element, left-ventricular canine models. In a preliminary study, the 2-D myocardial elastography was shown capable of imaging myocardial deformation comparable to equivalent tMRI estimates in a clinical setting.     

Carbon speciation of diesel exhaust and urban particulate matter NIST standard reference materials with C(1s) NEXAFS spectroscopy

The U.S. National Institute of Standards and Technology (NIST) provides a number of particulate matter (PM) standard reference materials (SRM) for use in environmental and toxicological methodology and research. We present here the first analysis with respect to the molecular structure of the carbon in three such NIST SRM samples, i.e., diesel engine exhaust soot from heavy duty equipment engines (SRM 1650), diesel soot from a forklift engine (SRM 2975), and urban PM collected in St. Louis, MO (SRM 1648), with near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The NEXAFS spectra of the two diesel soot samples appear quite similar, while they differ significantly from the urban PM spectrum, in agreement with X-ray diffraction data published recently. Such comparison is made in terms of aromatic and aliphatic carbon species, as well as by a general comparison with graphitic materials. Both diesel soot SRM samples contain basic graphitic structures, but the presence of exciton resonance and extended X-ray absorption fine structure oscillations in SRM 1650 and the lack therof in SRM 2975 suggest that SRM 1650 is the more graphitic material.The presence of polycyclic aromatic hydrocarbons, which have a characteristic NEXAFS resonance at the same position as graphite, can obscure the graphitic character of soot, unless an extraction of the organic matter is made. Our NEXAFS data do not suggest that the urban PM sample SRM 1648 contains a substantial amount of graphite-like material.     

Entering our 16th year

Background and objective

British American Tobacco (BAT) has historically enjoyed a monopoly position in Kenya. Analysis of recent tobacco control debates and a case study of BAT''s response to the emergence of competition in Kenya are used to explore the company''s ability to shape public policy and its treatment of tobacco farmers.

Design

Analysis of internal industry documents from BAT''s Guildford depository, other relevant data and interviews with key informants.

Results

BAT enjoys extensive high‐level political connections in Kenya, including close relationships with successive Kenyan presidents. Such links seems to have been used to influence public policy. Health legislation has been diluted and delayed, and when a competitor emerged in the market, BAT used its contacts to have the government pass legislation drafted by BAT that compelled farmers to sell tobacco to BAT rather than to its competitor. BAT was already paying farmers less than any other African leaf‐growing company, and the legislation entrenched poor pay and a quasi‐feudal relationship. BAT''s public relation''s response to the threat of competition and the ministers'' public statements extolling the economic importance of tobacco growing suggest that BAT has manipulated tobacco farming as a political issue.

Conclusions

The extent of BAT''s influence over public policy is consistent with the observations that, despite ratifying the Framework Convention on Tobacco Control, progress in implementing tobacco control measures in Kenya has been limited. The benefits of tobacco farming seem to be deliberately exaggerated, and an analysis of its true cost benefits is urgently needed. Tobacco farmers must be protected against BAT''s predatory practices and fully informed about its activities to help them have an informed role in policy debates. As image, particularly around the importance of tobacco farming, seems key to BAT''s ability to influence policy, the truth about its treatment of farmers must be publicised.Driven by the recent expansion of transnational tobacco corporations (TTCs) across many low‐ and middle‐income countries, the burden of tobacco''s health effect is shifting. It is predicted that, by 2030, 70% of the estimated 10 million global deaths from tobacco will occur in developing countries.¹ In this context, sub‐Saharan Africa (SSA) offers an opportunity for global health, being the only region in the world where primary prevention of the tobacco epidemic remains possible.² However, with TTCs investing heavily in the region during the last decade and with evidence of rapidly rising consumption, particularly among youth,³ this window of opportunity is closing rapidly.Implementation of comprehensive regulatory measures is required to prevent further escalation of the epidemic in SSA, and the World Health Organisation''s Framework Convention on Tobacco Control (FCTC) provides excellent opportunities in this regard. The African nations recognised this in pressing unanimously for a comprehensive treaty while simultaneously acknowledging the need to find an alternative income for countries dependent on tobacco farming, notably Zimbabwe and Malawi.^2,3 Tobacco farming represents a unique dimension to the tobacco control debate in SSA, and previous analyses of tobacco industry documents suggest that the tobacco industry has attempted to hijack such debates by presenting tobacco control as a “first world” concern that would lead to economic destabilisation and exacerbate poverty and malnutrition among tobacco‐growing countries.⁴ By contrast, a growing body of evidence suggests that tobacco farmers face considerable financial and health risks from growing tobacco.^{5,6,7,8,9,10,11,12}As African nations seek to implement the provisions of the FCTC, tobacco control legislation will have to be developed and enacted, providing opportunities for the tobacco industry to influence policy. The fact that Kenya has signed and ratified the FCTC¹³ while (as detailed below) efforts to implement legislation consistent with the treaty have been unsuccessful amid persistent reports of BAT influence¹⁴ highlights the possible barriers. Hence, there is an urgent need to understand the tobacco control policy environment in Africa, including the relationships between tobacco farmers and TTCs, which are clearly integral to this. However, there remains a dearth of research in this area. This paper seeks to address this gap by examining British American Tobacco''s (BAT) policy influence in Kenya.BAT merits particular attention as it is the dominant player in SSA, with a market share of over 90% in 11 countries.³ The selection of Kenya reflects its significance to BAT''s operations in Africa, the role it seems to have in BAT''s efforts to influence policy regionally¹⁵ and the nature of Kenyan tobacco politics.After an introduction to the origins and character of BAT''s political influence in Kenya and an overview of recent tobacco control debates in the country, this paper uses a case study of the company''s response to an emergent competitor, Mastermind Tobacco Kenya (referred to in the documents as MTK or MTCo), to examine BAT''s influence on policymaking. The paper therefore aims to shed important light on issues critical to the development of tobacco control across SSA.     

Anion binding involving pi-acidic heteroaromatic rings

Anions are essential species in biological systems and, particularly, in enzyme-substrate recognition. Therefore, the design and preparation of anion receptors is a topical field of supramolecular chemistry. Most host-guest systems successfully developed are based on noncovalent (ionic and hydrogen-bonded) interactions between anions and ammonium-type functionalities or Lewis acid groups. However, since the past 5 years, an alternative route toward the synthesis of efficient anion hosts has emerged, namely, the use of "anion-pi" interactions involving nitrogen-containing electron-deficient aromatic rings, as the result of several favorable theoretical investigations. In this Account, the state of the (new) art in this growing area of anion-binding research is presented and several selected examples from our work and that of other groups will be discussed.     

Wastes as co-fuels: the policy framework for solid recovered fuel (SRF) in Europe, with UK implications

European Union (EU) member states are adopting the mechanical-biological treatment (MBT) of municipal solid waste (MSW) to comply with EU Landfill Directive (LD) targets on landfill diversion. We review the policy framework for MSW-derived solid recovered fuel (SRF), composed of paper, plastic, and textiles, in the energy-intensive industries. A comparatively high calorific value (15-18 MJ/ kg) fuel, SRF has the potential to partially replace fossil fuel in energy-intensive industries, alongside MSW in dedicated combustion facilities. Attempts by the European standards organization (CEN) to classify fuel properties consider net calorific value (CV) and chlorine and mercury content. However, the particle size, moisture content, and fuel composition also require attention and future studies must address these parameters. We critically review the implications of using SRF as a co-fuel in thermal processes. A thermodynamic analysis provides insight into the technical and environmental feasibility of co-combusting SRF in coal-fired power plants and cement kilns. Results indicate the use of SRF as co-fuel can reduce global warming and acidification potential significantly. This policy analysis is of value to waste managers, policy specialists, regulators, and the waste management research community.     

Studying single-wall carbon nanotubes through encapsulation: from optical methods till magnetic resonance

Encapsulating fullerenes, magnetic fullerenes, 13C isotope enriched fullerenes, and organic solvents inside SWCNTs enables to yield unprecedented insight into their electronic, optical, and interfacial properties and to study SWCNT growth. In addition to customary methods of their studies such as e.g., optical absorption or Raman spectroscopy, these efforts enables to employ electron spin resonance (ESR) and nuclear magnetic resonance (NMR) spectroscopy. Encapsulated C60 fullerenes are transformed to inner tubes by a high temperature annealing. The diameter distribution of the inner tubes follow that of the outer ones and their unique, low defect concentration makes them an ideal model system for high resolution and energy dependent Raman studies. The observation of Raman modes of individual inner-outer tube pairs allows to measure the inner-outer tube interaction strength that is also well described theoretically. Reversible closing and opening of SWCNT can be studied in a diameter selective manner by encapsulating C60 and transforming it to an inner tube. The growth of inner tubes can be achieved from 13C enriched encapsulated organic solvents, which shows that the geometry of the fullerene does not play a particular role in the inner tube growth as it was originally thought. In addition, it opens new perspectives to explore the in-the-tube chemistry. Growth of inner tubes from 13C enriched fullerenes provides a unique isotope engineered heteronuclear system, where the outer tubes contain natural carbon and the inner walls are controllably 13C isotope enriched. The material enables to identify the vibrational modes of inner tubes which otherwise strongly overlap with the outer tube modes. The 13C NMR signal of the material has an unprecedented specificity for the small diameter SWCNTs. Temperature and field dependent 13C T1 studies show a uniform metallic-like electronic state for all inner tubes rather than distributed metallic and isolating behavior. A low energy, 3 meV gap is observed that is tentatively assigned to a long sought Peierls transition in the small diameter SWCNTs. Encapsulating magnetic fullerenes, such as N@C60 and C59N opens the way for local probe ESR studies of the electronic properties of the SWCNTs.