Optimized shapes of magnetic arrays for drug targeting applications

Arrays of permanent magnet elements have been utilized as light-weight, inexpensive sources for applying external magnetic fields in magnetic drug targeting applications, but they are extremely limited in the range of depths over which they can apply useful magnetic forces. In this paper, designs for optimized magnet arrays are presented, which were generated using an optimization routine to maximize the magnetic force available from an arbitrary arrangement of magnetized elements, depending on a set of design parameters including the depth of targeting (up to 50mm from the magnet) and direction of force required. A method for assembling arrays in practice is considered, quantifying the difficulty of assembly and suggesting a means for easing this difficulty without a significant compromise to the applied field or force. Finite element simulations of in vitro magnetic retention experiments were run to demonstrate the capability of a subset of arrays to retain magnetic microparticles against flow. The results suggest that, depending on the choice of array, a useful proportion of particles (more than 10%) could be retained at flow velocities up to 100 mm/s or to depths as far as 50mm from the magnet. Finally, the optimization routine was used to generate a design for a Halbach array optimized to deliver magnetic force to a depth of 50mm inside the brain

Formation of Metallurgical Coke within Minutes through Coal Densification and Microwave Energy

This paper shows how feedstock densification gives rise to a step change in the time required to create a metallurgical grade coke using microwave energy. Five densified coking and non-coking coals were heated in a multi-mode microwave 2450 MHz cavity for varying treatment times (2-20 minutes) with a fixed power input (6 kW). Proximate analysis, intrinsic reactivity, coke reactivity, dielectric properties, and petrographic analysis of the coals and microwave produced lump cokes were compared to a commercial lump coke. Densifying the sample prior to microwave treatment enabled a dramatic acceleration of the coking process when combined with targeted high microwave energy densities. It was possible to form fused coke lump structures with only 2 minutes of microwave heating compared to 16-24 hours via conventional coking. Anisotropic coke morphologies (lenticular and circular) were formed from non-coking coal that are not possible with conventional coking and increasing treatment time improved overall coke reflectance. Three of the coals produced coke with equivalent coke reactivity index values of 20-30, which are in the acceptable range for blast furnaces. The study demonstrated that via this process, non-coking coals could potentially be used to produce high quality cokes, potentially expanding the raw material options for metallurgical coke production

Separation of oil/water emulsions in continuous flow using microwave heating

This work studies a continuous flow microwave system to enhance gravity settling of water-in-oil emulsions. Settling times were found to be dependent upon the applied power, flowrate and energy input. Power and energy input are linked to liquid flowrate within the flow system used in this study, so a key objective of this work was to understand the effect of turbulence on the heating and separation of the flowing emulsion. At high flowrates (9 – 12 L/min) it was found that turbulence dominates, with settling times largely independent of energy input. At lower flowrates (1 - 6 L/min), when turbulence was decreased, it was found that the settling time decreased as the power density was increased. Settling times have the potential to be less than half that of untreated emulsions, and can be reduced further if turbulence can be minimised between the microwave heating zone and the settling zone in the process equipment

A review of microwave coal processing

This paper reviews the application of microwave energy in coal processing and utilisation. It covers a wide variety of processes including liberation of minerals, coal drying, pre-treatment to improve grindability, liquefaction enhancements and coke making. There is also consideration of analytical techniques that use microwave energy for continuous monitoring of coal feed systems. Where possible, industrial or pilot scale examples of these processes are discussed, along with a consideration of the significant hurdles that exist scaling from bench or pilot scale systems to industrial sized units. The processes with more immediate promise for scale-up are identified, as are those that require further laboratory scale experiments to establish whether microwave processing should be pursued at a larger scale. The importance of dielectric properties of the materials to be processed is emphasised, and the reasons behind the need for a multi-disciplinary approach to the design and operation of electromagnetic experiments are explained. Microwave coal processing is a diverse area, which has the potential to aid in coal upgrading, cleaning and comminution, thus improving efficiency and reducing harmful emissions of coal usage. Other promising research areas include the investigation of microwave processing for coking, liquefaction, enhancing fluid flow in coal beds and coal characterisation. However, due to the scale of most industrial coal processing systems and the lack of availability of microwave hardware at power levels of above 100 kW, commercial applications of microwaves for coal processing are still some if not many years away. Whilst there are some interesting applications from a scientific point of view, a very strong value proposition coupled with an organisation with high acceptance of risk would be required to develop high power microwave equipment able to work effectively in dirty, harsh environments

Factors affecting the microwave coking of coals and the implications on microwave cavity design

The work carried out in this paper assessed how processing conditions and feedstock affect the quality of the coke produced during microwave coke making. The aim was to gather information that would support the development of an optimised microwave coke making oven. Experiments were carried out in a non-optimised 2450 MHz cylindrical cavity. The effect of treatment time (15–120 min), power input (750 W–4.5 kW) and overall power input (1700–27,200 kWh/t) on a range of coals (semi-bituminous–anthracite) was investigated. Intrinsic reactivity, random reflectance, strength index and dielectric properties of the produced cokes were compared with those of two commercial cokes to assess the degree of coking produced in the microwave system. Overall energy input and coal rank were found to be the major factors determining the degree of coking following microwave treatment. The dependency on coal rank was attributed to the larger amount of volatiles that had to be removed from the lower ranked coals, and the increasing dielectric loss of the organic component of the coal with rank due to increased structural ordering. Longer treatment times at lower powers or shorter treatment times at higher powers are expected to produce the same degree of coking. It was concluded that microwave coke making represents a potential step-change in the coking industry by reducing treatment times by an order of magnitude, introducing flexibility and potentially decreasing the sensitivity to quality requirement in the feedstock. The main challenges to development are the energy requirements (which will need to be significantly reduced in an optimised process) and penetration depth (which will require an innovative reactor design to maximise the advantage of using microwaves). Understanding and quantifying the rapidly changing dielectric properties of the coal and coke materials is vital in addressing both of these challenges

Atom and step economical synthesis of acyclic quaternary centers via iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes

Quaternary benzylic centers are accessed with high atom and step economy by Ir-catalyzed alkene hydroarylation. These studies provide unique examples of the use of non-polarized 1,1-disubstituted alkenes in branch selective Murai-type hydro(hetero)arylations. Detailed mechanistic studies have been undertaken, and these indicate that the first irreversible step is the demanding alkene carbometallation process. Structure-reactivity studies show that the efficiency of this is critically dependent on key structural features of the ligand. Computational studies have been undertaken to rationalize this experimental data, showing how more sterically demanding ligands reduce the reaction barrier via predistortion of the reacting intermediate. The key insight disclosed here will underpin the ongoing development of increasingly sophisticated branch selective Murai hydroarylations

Magnetically Responsive Microbubbles as Delivery Vehicles for Targeted Sonodynamic and Antimetabolite Therapy of Pancreatic Cancer

Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3% reduction in tumour volume relative to an untreated control group (p<0.05) when the tumour was exposed to both external magnetic and ultrasound fields during administration of the MagMBs. In contrast, application of an external ultrasound field alone resulted in a 27% reduction in tumour volume. In addition, activated caspase and BAX protein levels were both observed to be significantly elevated in tumours harvested from animals treated with the MagMBs in the presence of magnetic and ultrasonic fields when compared to expression of those proteins in tumours from either the control or ultrasound field only groups (p<0.05). These results suggest MagMBs have considerable potential as a platform to enable the targeted delivery of combined sonodynamic / antimetabolite therapy in pancreatic cancer

Sustained Reduction in Third-generation Cephalosporin Usage in Adult Inpatients Following Introduction of an Antimicrobial Stewardship Program in a Large, Urban Hospital in Malawi

Background Third-generation cephalosporins (3GC) remain the first-choice empiric antibiotic for severe infection in many sub-Saharan African hospitals. In Malawi, limited availability of alternatives, mean that strategies to prevent spread of 3GC-resistance (3GC-R) are imperative, however suitable approaches to antimicrobial stewardship (AMS) in low-income settings are not well studied. Methods We introduced an AMS intervention to Queen Elizabeth Central Hospital (QECH) in Blantyre. The intervention consisted of a smartphone prescribing application and regular point-prevalence surveys (PPS) with prescriber feedback. We evaluate the effects of the intervention on 3GC usage and on cost of providing antibiotics. Using thematic analysis of semi-structured interviews and participant observations, we additionally evaluate the acceptability of the stewardship program. Results The proportion of antibiotic prescriptions for a 3GC reduced from 193/241 (80.1%) to 177/330 (53.6%) (percentage decrease 26.5% [95%CI; 18.7 to 34.1]) with no change in case-fatality rate. Cost analysis estimated annual savings of US$15,000. Qualitative research revealed trust in the guideline and found its accessibility through smartphones helpful to guide clinical decisions. Operational health-system barriers and hierarchal clinical relationships lead to continued reliance on 3GC. Conclusions We report the successful introduction of an antimicrobial stewardship approach in Malawi. By focusing on pragmatic interventions and simple aims, we demonstrate the feasibility, acceptability and cost-saving of a stewardship program where resources are limited. In doing so, we provide a suitable starting point for expansion of AMS interventions in this and other low-income settings