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Cost of Environmental Litigation:R (Edwards) v Environment Agency (No.2)
No full textCase-note on Supreme Court resolution of case about litigation expense
Magnetic retraction of bowel by intraluminal injectable cyanoacrylate-based magnetic glue
No full textMagnetic retraction offers advantages over physical retraction by graspers because of reduced tissue trauma. The objectives of this study are to investigate a novel method of magnetisation of bowel segments by intraluminal injection of magnetic glue and to demonstrate the feasibility of magnetic retraction of bowel with sufficient force during minimal access surgery. Following an initial materials characterisation study, selected microparticles of stainless steel (SS410-µPs) were mixed with chosen cyanoacrylate glue (Loctite 4014). During intraluminal injection of the magnetic glue using ex vivo porcine colonic segments, a magnetic probe placed at the injected site ensured that the SS410-µPs aggregated during glue polymerisation to form an intraluminal mucosally adherent coagulum. The magnetised colonic segments were retracted by magnetic probes (5 and 10?mm) placed external to the bowel wall. A tensiometer was used to record the retraction force. With an injected volume of 2?mL in a particle concentration of 1?g/mL, this technique produced maximal magnetic retraction forces of 2.24 ± 0.23?N and 5.11 ± 0.34?N (n=20), with use of 5 and 10?mm probes, respectively. The results indicate that the formation of an intraluminal coagulum based on SS410-µPs and Loctite 4014 produces sufficient magnetic retraction for bowel retraction
Synthesis and biological evaluation of phosphate Prodrugs of 4-Phospho-D-erythronohydroxamic acid, an inhibitor of 6-phosphogluconate dehydrogenase
No full textWe have previously reported the discovery of potent and selective inhibitors of 6-phosphogluconate dehydrogenase, the third enzyme of the phosphate pentose pathway, from Trypanosoma brucei, the causative organism of human African trypanosomiasis. These inhibitors were charged phosphate derivatives with restricted capacity to enter cells. Herein, we report the synthesis of five different classes of prodrugs: phosphoramidate; bis-S-acylthioethyl esters (bis-SATE); bis-pivaloxymethyl (bis-POM); CycloSaligenyl; and phenyl, S-acyl thioethyl mixed phosphate esters (mix-SATE). Prodrugs were studied for stability and activity against the intact parasites. Most prodrugs caused inhibition of the growth of the parasites. The activity of the prodrugs against the parasites appeared to be related to their stability in aqueous buffer.</p
Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma
No full textStatins have anti-inflammatory properties that may be beneficial in the treatment of asthma. A study was undertaken to test the hypothesis that atorvastatin added to inhaled corticosteroids improves lung function and airway inflammation in atopic adults with asthma
Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis
No full textObjectives The purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS).Background Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling.Methods The Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (> 110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations).Results A total of 2,117 patients with AS (mean age 73 +/- 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis.Conclusions This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS. (J Am Coll Cardiol 2011;58:570-6) (C) 2011 by the American College of Cardiology Foundation</p
Design, Synthesis and Biological Evaluation of Novel Inhibitors of Trypanosoma brucei Pteridine Reductase 1
No full textGenetic studies indicate that the enzyme pteridine reductase 1 (PTR1) is essential for the survival of the protozoan parasite Trypanosoma brucei. Herein, we describe the development and optimisation of a novel series of PTR1 inhibitors, based on benzo[d]imidazol-2-amine derivatives. Data are reported on 33 compounds. This series was initially discovered by a virtual screening campaign (J. Med. Chem., 2009, 52, 4454). The inhibitors adopted an alternative binding mode to those of the natural ligands, biopterin and dihydrobiopterin, and classical inhibitors, such as methotrexate. Using both rational medicinal chemistry and structure-based approaches, we were able to derive compounds with potent activity against T. brucei PTR1 (K-i(app) = 7 nm), which had high selectivity over both human and T. brucei dihydrofolate reductase. Unfortunately, these compounds displayed weak activity against the parasites. Kinetic studies and analysis indicate that the main reason for the lack of cell potency is due to the compounds having insufficient potency against the enzyme, which can be seen from the low K-m to K-i ratio (K-m = 25 nm and K-i = 2.3 nm, respectively).</p
Diversity oriented syntheses of fused pyrimidines designed as potential antifolates
No full textDiversity oriented syntheses of some furo[2,3-d]pyrimidines and pyrrolo[2,3-d] pyrimidines related to folate, guanine, and diaminopyrimidine-containing drugs have been developed for the preparation of potential anti-infective and anticancer compounds. Amide couplings and Suzuki couplings on the basic heterocyclic templates were used, in the latter case yields being especially high using aromatic trifluoroborates as the coupling partner. A new ring synthesis of 6-aryl-substituted deazaguanines bearing 2-alkylthio groups has been developed using Michael addition of substituted nitrostyrenes. Diversity at C-2 has been introduced by oxidation and substitution with a range of amino nucleophiles. The chemical reactivity of these pyrrolopyrimidines with respect to both electrophilic substitution in ring synthesis and nucleophilic substitution for diversity is discussed. Several compounds were found to inhibit pteridine reductases from the protozoan parasites Trypanosoma brucei and Leishmania major at the micromolar level and to inhibit the growth of Trypanosma brucei brucei in cell culture at higher concentrations. From these results, significant structural features required for inhibition of this important drug target enzyme have been identified.</p
Nanosecond pulsed laser blackening of copper
No full textNanosecond (12ns) pulsed laser processing of copper at 532nm resulted in the formation of homogenously distributed, highly organized microstructures. This led to the fabrication of large area black copper substrates with absorbance of over 97% in the spectral range from 250 nm to 750nm, and a broadband absorbance of over 80% between 750nm and 2500nm. Optical and chemical analyses of the fabricated black metal are presented and discussed. The employed laser is an industrially adaptable source and the presented technique for fabrication of black copper could find applications in broadband thermal radiation sources, solar energy absorbers, irradiative heat transfer devices, and thermophotovoltaics
Hybrid Tribunals at Ten:How International Criminal Justice’s Golden Child Became an Orphan
No full textSmoke and Mirrors:construction, trickery and surface in my work from a historical perspective
No full textAn article which assesses the role of materiality in Colvin's work, and particularly it’s significance in relation to the visual, literary and scientific themes explored within these works, seen in relation to the three-dimensional explorations of my recent ‘Natural Magic’ exhibition. The article was developed from an invited paper given at the SSHoP conference Photography in Scotland: 'then, now and beyond our time' at the Hawthornden Lecture Theatre, National Gallery, Edinburgh 27-28th March 2009.The article explores ideas of surface texture in the photographic image as a conceptual element, a theme which has become apparent through recent bodies of work in conjunction with technological developments in photography. A range of work is discussed in relation to methods of print production utilized for each project. Through this narrative Colvin discusses ideas inherent in the projects, and present an alternative reading of the works. This ‘exploration’ of surface image is presented predominantly through trompe l'oeil works, creating the impression of a surface that has a different three-dimensional structure to the painting. Initially Colvin turned the trompe l'oeil issue on its head - making the solid look flat. Colvin painted over three-dimensional structures and alignment was maintained because the final scene was photographed from the only point where this was possible. When viewing these photographs, the solid scene is initially overlooked and pictorial flatness dominates perception. With more protracted viewing, the objects in the scene emerge and a strange tension is introduced between the solid and the flat, between the scene and the seen. Objects in three dimensions are intentionally merged in the picture plane - and their identity is perceived after the flatness is transcended. The works in the ‘Natural Magic’ series represent a further development, and their conceptual and visual significance is discussed here
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