A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea

Background: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID).

Methods: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1-2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4mg then 8mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements.

Results: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio = 2.0, 90% confidence interval: 0.9-4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P = 0.05) and at the 8-mg dose level (P = 0.02) compared with placebo.

Conclusion: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.

The Potential of a New Type of Carburettor to Assist SORE in Meeting EPA / CARB Phase 3 Legislation

Small off-road engines (SORE) have been recognised as a major source of air pollution. It is estimated that non handheld SORE annually produce over 1 million tonnes of HC+NOx and over 50 million tonnes of CO2. The fuel system design and its operating AFR are of key importance with regard to engine operation and engine out emissions. The conventional low-cost float carburettors used in these engines are relatively ineffective at atomising and preparing the fuel for combustion requiring a rich setting for acceptable functional performance. EPA and CARB have confirmed that Phase 3 limits are achievable for a “durable” engine fitted with a conventional well calibrated and manufactured “stock rich setting” float carburettor together with catalytic oxidation after-treatment and passive secondary air injection. The EPA and CARB strategy for meeting Phase 3 only considers the use of conventional float carburettors that operate at rich AFR’s over their entire engine operating range as no other cost effective alternative fuel system is yet available on the market. A cost effective alternative to the conventional carburettor that enabled leaner or optimised AFR operation with load and improved combustion performance would open the door to alternative strategies to meeting the phase 3 limits. This paper presents a completely new form of mechanical carburettor that gives AFR control with load, improved mixture preparation for improved combustion performance and has a lower production cost than conventional carburettors. The conventional and new fuel system designs and operation are discussed in detail and their technical merits demonstrated in the form of engine test data. The performance of different after-treatment systems is also simulated for different AFR profiles with load for a conventional or unmodified SORE engine. With optimised leaner operation and improved combustion characteristics, this new carburettor technology can provide significant engine out CO and HC+NOx reductions on the J1088 test cycle without loss of functional performance. Depending on the chosen emissions control strategy, minimum engine out emissions or optimum engine AFR for oxidation or three-way after-treatment or another, this new carburettor technology can be easily calibrated to provide the desired engine operating AFR profile on the J1088 cycle.

Student Teachers’ Perceptions of the Effectiveness of their Initial Preparation

What influences how well-prepared student teachers feel towards working in schools upon completion of their initial teacher preparation (ITP)? In order to investigate this question, we used a path analysis using data from a longitudinal study investigating the experiences of trainee and early career phase teachers in England. The data were generated via self-complete questionnaires and follow-up telephone interviews with 1,322 trainees. Those on undergraduate or school-based programmes felt better prepared to work as teachers than one-year postgraduate trainees, perhaps because the former give higher ratings of the quality of assessment of, and feedback received on, teaching practice, and because of the clarity of theory-practice links in programmes. Across different kinds of ITP programme, good relationships with school-based mentors significantly boosted trainees' confidence that their ITP had effectively prepared them for teaching. Trainees' motives for entering the profession and their initial concerns about and expectations of ITP also affected their perceptions of its effectiveness, by shaping the way they experienced aspects of their courses. Implications of these findings for policy and practice in teacher preparation are discussed. © 2011 Blackwell Publishing Ltd.

Solvent induced phase inversion-based in situ forming controlled release drug delivery implants

In situ forming (ISF) drug delivery implants have gained tremendous levels of interest over the last few decades. This is due to their wide range of biomedical applications such as in tissue engineering, cell encapsulation, microfluidics, bioengineering and drug delivery. Drug delivery implants forming upon injection has shown a range of advantages which include localized drug delivery, easy and less invasive application, sustained drug action, ability to tailor drug delivery, reduction in side effects associated with systemic delivery and also improved patient compliance and comfort. Different factors such as temperature, pH, ions, and exchange of solvents are involved in in situ implant formation. This review especially focuses on ISF implants that are formed through solvent induced phase inversion (SPI) technique. The article critically reviews and compares a wide range of polymers, solvents, and co-solvents that have been used in SPI implant preparation for control release of a range of drug molecules. Major drawback of SPI systems has been their high burst release. In this regard, the article exhaustively discusses factors that affect the burst release and different modification strategies that has been utilised to reduce the burst effect from these implants. Performance and controversial issues associated with the use of different biocompatible solvents in SPI systems is also discussed. Biodegradation, formulation stability, methods of characterisation and sterilisation techniques of SPI systems is comprehensively reviewed. Furthermore, the review also examines current SPI-based marketed products, their therapeutic application and associated clinical data. It also exemplifies the interest of multi-billion dollar pharma companies worldwide for further developments of SPI systems to a range of therapeutic applications. The authors believe that this will be the first review article that extensively investigate and discusses studies done to date on SPI systems. In so doing, this article will undoubtedly serve as an enlightening tool for the scientists working in the concerned area.

Micromaser spectrum and phase diffusion dynamics

We discuss a scheme to relate the phase diffusion dynamics of the micromaser field to the measured atomic population statistics. This can allow us to measure the linewidth of the micromaser spectrum and to solve a relevant decoherence problem in cavity quantum electrodynamics. The main steps are (i) a suitable preparation of the cavity field state to generate coherences, (ii) the transfer of information on the dynamics of field coherences to probe atoms by the action of an external resonant coherent field and (iii) the derivation of the phase diffusion rate, hence the micromaser linewidth, from the measured population statistics of the probe atoms. The method can be applied even in the presence of trapping states, where peculiar linewidth oscillations are expected for increasing pump rate, due to the quantum nature of the micromaser field.

Mechanochemical preparation of Ag catalysts for the n-octane-SCR de-NOx reaction: Structural and reactivity effects

Mechanochemical preparation of Ag/Al2O3 catalysts used for the selective catalytic reduction of NOx using hydrocarbons has been shown to substantially increase the activity of the catalyst in comparison with Ag/Al2O3 prepared by wet impregnation. The effect of using different ball-milling experimental parameters on both the structure of the material as well as the catalyst activity has been investigated and the optimum conditions established. A phase transition from γ- to α-alumina was observed milling at high speeds which was found to result in lower catalyst activities. At lower milling speeds both fracturing and agglomeration of the alumina support can be observed depending on the grinding time. However, due to ball-milling, a general enhancement in the NOx reduction activity was observed for all catalysts compared with the conventionally prepared catalysts irrespective of the reductant used. Transient DRIFTS-MS experiments were performed to investigate the effect of H2 in the absence and presence of water on the SCR reaction over catalysts prepared by both ball milling and wet impregnation. In-situ DRIFTS-MS analysis revealed significant differences in both gas phase and surface species. Most notably, isocyanate species were formed significantly more quickly and at higher surface concentration in the case of the mechanochemically prepared catalyst.

Synthesis by extrusion: continuous, large-scale preparation of MOFs using little or no solvent

Grinding solid reagents under solvent-free or low-solvent conditions (mechanochemistry) is emerging as a general synthetic technique which is an alternative to conventional solvent-intensive methods. However, it is essential to find ways to scale-up this type of synthesis if its promise of cleaner manufacturing is to be realised. Here, we demonstrate the use of twin screw and single screw extruders for the continuous synthesis of various metal complexes, including Ni(salen), Ni(NCS)(2)(PPh3)(2) as well as the commercially important metal organic frameworks (MOFs) Cu-3(BTC)(2) (HKUST-1), Zn(2-methylimidazolate)(2) (ZIF-8, MAF-4) and Al(fumarate)(OH). Notably, Al(fumarate)(OH) has not previously been synthesised mechanochemically. Quantitative conversions occur to give products at kg h(-1) rates which, after activation, exhibit surface areas and pore volumes equivalent to those of materials produced by conventional solvent-based methods. Some reactions can be performed either under completely solvent-free conditions whereas others require the addition of small amounts of solvent (typically 3-4 mol equivalents). Continuous neat melt phase synthesis is also successfully demonstrated by both twin screw and single screw extrusion for ZIF-8. The latter technique provided ZIF-8 at 4 kg h(-1). The space time yields (STYs) for these methods of up to 144 x 10(3) kg per m(3) per day are orders of magnitude greater than STYs for other methods of making MOFs. Extrusion methods clearly enable scaling of mechanochemical and melt phase synthesis under solvent-free or low-solvent conditions, and may also be applied in synthesis more generally.

Preparation of La2NiO4+δ powders as a cathode material for SOFC via a PVP-assisted hydrothermal route

Uniform submicron La₂NiO_4+δ (sm-LNO) powders have been synthesized by a facile polyvinylpyrrolidone (PVP)-assisted hydrothermal route. In the presence of PVP, sm-LNO of pure phase has been obtained by calcination at the relatively low temperature of 900 °C for 8 h. Compared micron-sized LNO (m-LNO) particles obtained at 1,000 °C by hydrothermal synthesis route without PVP assisted, the sm-LNO-PVP displays regularly shaped and well-distributed particles in the range of 0.3–0.5 μm. The scanning electron microscopy (SEM) results showed that the sm-LNO sample is submicronic and that the m-LNO sample shows agglomerates with a broad size distribution. The electrochemical performance of m-LNO and sm-LNO-PVP has been investigated by electrochemical impedance spectroscopy. The polarization resistance of the sm-LNO-PVP cathode reaches a value of 0.40 Ω cm² at 750 °C, which is lower than that of m-LNO (0.62 Ω cm²). This result indicates that a fine electrode microstructure with submicron particles can help to increase the active sites, accelerate oxygen diffusion, and reduce polarization resistance. An anode-supported single cell with sm-LNO cathode has been fabricated and tested over a temperature range from 650 to 800 °C. The maximum power density of the cell has achieved 834 mW cm⁻² at 750 °C. These results therefore show that this PVP-assisted hydrothermal method is an effective approach to construct submicron-structured cathode and enhance the performance of intermediate temperature solid oxide fuel cell.

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by dietinduced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice.

Comparison of Disposable Pipette Extraction and Dispersive Solid-Phase Extraction in the QuEChERS Method for Analysis of Pesticides in Strawberries

In this study, we sought to assess the applicability of GC–MS/MS for the identification and quantification of 36 pesticides in strawberry from integrated pest management (IPM) and organic farming (OF). Citrate versions of QuEChERS (quick, easy, cheap, effective, rugged and safe) using dispersive solid-phase extraction (d-SPE) and disposable pipette extraction (DPX) for cleanup were compared for pesticide extraction. For cleanup, a combination of MgSO4, primary secondary amine and C18 was used for both the versions. Significant differences were observed in recovery results between the two sample preparation versions (DPX and d-SPE). Overall, 86% of the pesticides achieved recoveries (three spiking levels 10, 50 and 200 µg/kg) in the range of 70–120%, with <13% RSD. The matrix effects were also evaluated in both the versions and in strawberries from different crop types. Although not evidencing significant differences between the two methodologies were observed, however, the DPX cleanup proved to be a faster technique and easy to execute. The results indicate that QuEChERS with d-SPE and DPX and GC–MS/MS analysis achieved reliable quantification and identification of 36 pesticide residues in strawberries from OF and IPM.

OFFLINE AND ONLINE SOLID PHASE EXTRACTION/PRECONCENTRATION OF INORGANICS

Solid phase extraction (SPE) is a powerful technique for preconcentration/removal or separation of trace and ultra trace amounts of toxic and nutrient elements. SPE effectively simplifies the labour intensive sample preparation, increase its reliability and eliminate the clean up step by using more selective extraction procedures. The synthesis of sorbents with a simplified procedure and diminution of the risks of errors shows the interest in the areas of environmental monitoring, geochemical exploration, food, agricultural, pharmaceutical, biochemical industry and high purity metal designing, etc. There is no universal SPE method because the sample pretreatment depends strongly on the analytical demand. But there is always an increasing demand for more sensitive, selective, rapid and reliable analytical procedures. Among the various materials, chelate modified naphthalene, activated carbon and chelate functionalized highly cross linked polymers are most important. In the biological and environmental field, large numbers of samples are to be analysed within a short span of time. Hence, online flow injection methods are preferred as they allow extraction, separation, identification and quantification of many numbers of analytes. The flow injection online preconcentration flame AAS procedure developed allows the determination of as low as 0.1 µg/l of nickel in soil and cobalt in human hair samples. The developed procedure is precise and rapid and allows the analysis of 30 samples per hour with a loading time of 60 s. The online FI manifold used in the present study permits high sampling, loading rates and thus resulting in higher preconcentration/enrichment factors of -725 and 600 for cobalt and nickel respectively with a 1 min preconcentration time compared to conventional FAAS signal. These enrichment factors are far superior to hitherto developed on line preconcentration procedures for inorganics. The instrumentation adopted in the present study allows much simpler equipment and low maintenance costs compared to costlier ICP-AES or ICP-MS instruments.

Preparation of high surface area TiO (anatase) by thermal hydrolysis 2 of titanyl sulphate solution

Highly crystalline, ultra fine TiO (anatase) having high surface area has been prepared by thermal hydrolysis of titanyl sulphate 2 solution and characterized using B.E.T surface area measurements, XRD and chemical analysis. The dependence of surface area on concentration of staffing solution, temperature of hydrolysis, duration of boiling and calcination temperature were also studied. As the boiling temperature, duration of boiling and calcination temperature increased, the surface area of TiO formed decreased significantly. 2 On increasing calcination temperature, the crystallite size of TiO also increased and gradually the phase transformation to rutile took 2 place. The onset and completion temperatures of rutilation were 700 and 10008C, respectively

Preparation and characterization of nanocrystalline transition metal-loaded sulfated titania through sol-gel method

Transition metal-loaded (3%) nanocrystalline sulfated titania (ST) powders are prepared using the sol–gel technique. Anatase is found as the active phase in all the samples. Sulfate ion impregnation decreases the crystallite size and stabilizes the anatase phase of TiO2. Acidity of the samples is found to increase by the incorporation of sulfate ion and also by the modification by transition metal ions. All the prepared catalysts are found stable up to 700 °C.

Liquid phase benzoylation of arenes over iron promoted sulphated zirconia

The present work undertakes the preparation and physico-chemical characterisation of iron promoted sulphated zirconia (SZ) with different amounts of iron loading and their application to Friedel-Crafts benzoylation of benzene, toluene and xylene under different experimental conditions, XRD and laser Raman techniques reveal the stabilisation of the tetragonal phase of zirconia and the existence of iron in highly dispersed form as Fe203 on the catalyst surface. The surface acidic properties were determined by ammonia temperature programmed desorption (TPD) and perylene adsorption, The results were supported by the TGA studies after adsorption of pyridine and 2,6-dimethylpyridine (2,6-DMP), Strong Lewis acid sites on the surface, which are evident from TPD and perylene adsorption studies. explain the high catalytic activity of the systems towards benzoylation. The experimental results provide evidence for the truly heterogeneous nature of the reaction. The studies also establish the resistance to deactivation in the metal incorporated sulphated systems.

Studies On Preparation And Characterization Of Hts Current Leads Using Multifilamentary Ag And Ag-Alloy Sheathed (Bi,Pb)-2223 Superconducting Tapes

The application vistas of superconductors have widened very much since the discovery of high TC superconductors (HTS) as many of the applications can be realised at 77 K rather than going down to 4.2 K, the liquid He temperature. One such application is the HTS current lead which is used to connect a superconducting system with a room temperature power source. Minimising heat leak to the cryogenic environment is the main advantage of introducing current leads into superconducting systems. The properties of HTSS likes zero resistance (avoiding joule heating) and very low thermal conductivity (minimized conductive heat transfer) make them ideal candidates to be used as current leads. There are two forms of HTS current leads. (i) bulk form (tube or rod) prepared either from YBCO or BSCCO and (ii) tape form prepared from Bi-2223 multifilamentary tapes. The tape form of current leads has many advantages with respect to the mechanical and thermal stability related criteria. Crucial information on various aspects of HTS current lead development are not available in the literature as those are kept proprietary by various companies around the world. The present work has been undertaken to tailor the properties of multifilamentary tapes for the current lead application and to optimise the processing parameters of the same for enhanced critical current density and field tolerance. Also it is the aim of the present investigation is to prepare prototype current leads engineered for operation in conduction cooled mode and test them for operational stability