Time scale in concrete fracture: a model based on partitions of unity

Intense research efforts have been put in the formulation of theories for crack initiation and propagation in concrete. Yet, little attention has been paid to the time-dependence of fracture, despite evidence of its significance. This paper reports a finite element model which captures the time scale in concrete fracture. Visco-elasticity is employed to capture bulk creep. In the fracture process zone a different time scale acts. Therefore, a rate-dependent cracking resistance is modelled. A recently developed finite element method for modelling cohesive cracks is employed. It is based on partitions of unity, by which means displacement jumps are introduced independently of the mesh structure. This avoids the requirement of dense meshes by regularised continuum approaches to model localisation, and a priori knowledge of where cracks occur for standard discrete cracking approaches via interfaces

A controlled trial of natalizumab for relapsing multiple sclerosis.

Background: In patients with multiple sclerosis, inflammatory brain lesions appear to arise from autoimmune responses involving activated lymphocytes and monocytes. The glycoprotein (alpha)(sub 4) integrin is expressed on the surface of these cells and plays a critical part in their adhesion to the vascular endothelium and migration into the parenchyma. Natalizumab is an (alpha)(sub 4) integrin antagonist that reduced the development of brain lesions in experimental models and in a preliminary study of patients with multiple sclerosis.Methods: In a randomized, double-blind trial, we randomly assigned a total of 213 patients with relapsing-remitting or relapsing secondary progressive multiple sclerosis to receive 3 mg of intravenous natalizumab per kilogram of body weight (68 patients), 6 mg per kilogram (74 patients), or placebo (71 patients) every 28 days for 6 months. The primary end point was the number of new brain lesions on monthly gadolinium-enhanced magnetic resonance imaging during the six-month treatment period. Clinical outcomes included relapses and self-reported well-being.Results: There were marked reductions in the mean number of new lesions in both natalizumab groups: 9.6 per patient in the placebo group, as compared with 0.7 in the group given 3 mg of natalizumab per kilogram (P<0.001) and 1.1 in the group given 6 mg of natalizumab per kilogram (P<0.001). Twenty-seven patients in the placebo group had relapses, as compared with 13 in the group given 3 mg of natalizumab per kilogram (P=0.02) and 14 in the group given 6 mg of natalizumab per kilogram (P=0.02). The placebo group reported a slight worsening in well-being (a mean decrease of 1.38 mm on a 100-mm visual-analogue scale), whereas the natalizumab groups reported an improvement (mean increase of 9.49 mm in the group given 3 mg of natalizumab per kilogram and 6.21 mm in the group given 6 mg of natalizumab per kilogram).Conclusions: In a placebo-controlled trial, treatment with natalizumab led to fewer inflammatory brain lesions and fewer relapses over a six-month period in patients with relapsing multiple sclerosis

Liver transplantation for glycogen storage disease types I, III, and IV

Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of liver adenoma and renal insufficiency. Nine type I and 3 type III patients have received liver transplants because of poor metabolic control, multiple liver adenomas, or progressive liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were liver transplanted because of progressive liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making. Conclusion Liver transplantation should be considered for patients with glycogen storage disease who have developed liver malignancy or hepatic failure, and for type IV patients with the classical and progressive hepatic form

Factors affecting airport route development activity and performance

Airports have become increasingly active in route development as a means of attracting, growing and retaining air services. However, little is known about the different levels of route development activity at airports, or the extent to which route development activity affects performance. Based on the findings of a survey of 124 airports worldwide, this study finds that larger airports are significantly more active than smaller airports. It also finds that private airports are more active than public airports, and that airports in Europe are more active than airports in other world regions, although differences according to ownership and location are not significant. Route development activity has a significant positive effect on performance. Factors associated with the airport business environment (market turbulence, competitive intensity, market growth and airport constraints) were not found to have a significant moderating effect on the relationship between route development activity and performance. However, two factors were found to have a significant direct effect on performance; market growth has a significant positive effect while airport constraints have a significant negative effect

Sources of land-derived runoff to a coral reef-fringed embayment identified using geochemical tracers in nearshore sediment traps

This paper is not subject to U.S. copyright. The definitive version was published in Estuarine, Coastal and Shelf Science 85 (2009): 459-471, doi:10.1016/j.ecss.2009.09.014.Geochemical tracers, including Ba, Co, Th, 7Be, 137Cs and 210Pb, and magnetic properties were used to characterize terrestrial runoff collected in nearshore time-series sediment traps in Hanalei Bay, Kauai, during flood and dry conditions in summer 2006, and to fingerprint possible runoff sources in the lower watershed. In combination, the tracers indicate that runoff during a flood in August could have come from cultivated taro fields bordering the lower reach of the river. Land-based runoff associated with summer floods may have a greater impact on coral reef communities in Hanalei Bay than in winter because sediment persists for several months. During dry periods, sediment carried by the Hanalei River appears to have been mobilized primarily by undercutting of low 7Be, low 137Cs riverbanks composed of soil weathered from tholeiitic basalt with low Ba and Co concentrations. Following a moderate rainfall event in September, high 7Be sediment carried by the Hanalei River was probably mobilized by overland flow in the upper watershed. Ba-desorption in low-salinity coastal water limited its use to a qualitative runoff tracer in nearshore sediment. 210Pb had limited usefulness as a terrestrial tracer in the nearshore due to a large dissolved oceanic source and scavenging onto resuspended bottom sediment. 210Pb-scavenging does, however, illustrate the role resuspension could play in the accumulation of particle-reactive contaminants in nearshore sediment. Co and 137Cs were not affected by desorption or geochemical scavenging and showed the greatest potential as quantitative sediment provenance indicators in material collected in nearshore sediment traps

Extraction and sensitive detection of toxins A and B from the human pathogen Clostridium difficile in 40 seconds using microwave-accelerated metal-enhanced fluorescence.

Clostridium difficile is the primary cause of antibiotic associated diarrhea in humans and is a significant cause of morbidity and mortality. Thus the rapid and accurate identification of this pathogen in clinical samples, such as feces, is a key step in reducing the devastating impact of this disease. The bacterium produces two toxins, A and B, which are thought to be responsible for the majority of the pathology associated with the disease, although the relative contribution of each is currently a subject of debate. For this reason we have developed a rapid detection assay based on microwave-accelerated metal-enhanced fluorescence which is capable of detecting the presence of 10 bacteria in unprocessed human feces within 40 seconds. These promising results suggest that this prototype biosensor has the potential to be developed into a rapid, point of care, real time diagnostic assay for C. difficile

Forty years on: clathrin-coated pits continue to fascinate

Clathrin mediated endocytosis (CME) is a fundamental process in cell biology and has been extensively investigated throughout the last several decades. Every cell biologist learns about it at some point during their education and the beauty of this process has led many of us to go deeper and make it the topic of our own research. Great progress has been made towards elucidating the mechanisms of CME and the field is becoming increasingly complex with several hundred new publications every year. This makes it easy to get lost in the vast amount of literature and to forget about the fundamentals of the field, based on the careful interpretation of simple observations made over 40 years ago. A study performed by Anderson, Brown and Goldstein in 1977 (Anderson et al., 1977) is a prime example of this. We therefore want to take a step back and examine how this seminal study was pivotal to our understanding of CME and its progression into ever increasing complexity over the last four decades

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Ultra-low timing jitter, Ti:Al2O3 synchronisation for stimulated Raman scattering and pump-probe microscopy

This is the final version. Available from SPIE via the DOI in this recordSignificance: Stimulated Raman scattering and pump-probe microscopy are implementations of multiphoton microscopy that acquire high-resolution, label-free images of live samples encoded with molecular contrast. Most commercial multiphoton microscopes cannot access these techniques since they require sample illumination by two temporally synchronised ultrafast modelocked pulse trains. Here, we present a compact and robust way of synchronising an additional Ti:Sapphire laser with a conventional single beam multiphoton microscope to realise an instrument that can acquire images with enhanced molecular specificity. Aim: A passive optical synchronisation scheme for a pair of commercially available, unmodified modelocked Ti:Sapphire lasers was developed. The suitability of this synchronisation scheme for advanced biomedical microscopy was investigated. Approach: A pair of modelocked Ti:Sapphire lasers were aligned in master-slave configuration. 5% of the master laser output was used to seed the modelocking in the slave laser cavity. The timing jitter of the master and slave pulse trains was characterised using an optical autocorrelator. The synchronised output of both lasers was coupled into a laser scanning microscope and used to acquire spectral focussing stimulated Raman scattering and pump-probe microscopy images from biological and non-biological samples. Results: A timing jitter between the modelocked pulse trains of 0.74 fs was recorded. Spectral focussing stimulated Raman scattering allowed spectral discrimination of polystyrene and polymethyl methacrylate beads. Pump-probe microscopy was used to record excited state lifetime curves from haemoglobin in intact red blood cells. Conclusion: This work demonstrates a simple and robust method of upgrading single beam multiphoton microscopes with an additional ultrafast laser. The resulting dual-beam instrument can be used to acquire label-free images of sample structure and composition with high biochemical specificity.Biotechnology & Biological Sciences Research Council (BBSRC)Wellcome Trus

Overview of a paediatric renal transplant programme

INTRODUCTION: Renal transplantation is the therapy of choice for children with end-stage renal failure. There are many challenges associated with a paediatric programme in a developing country where organs are limited. METHODS: A retrospective review was undertaken of 149 paediatric renal transplants performed between 1968 and 2006 with specific emphasis on transplants performed in the last 10 years. Survival of patients and grafts was analysed and specific problems related to drugs and infections were reviewed. RESULTS: On review of the total programme, 60% of the transplants have been performed in the last 10 years, with satisfactory overall patient and graft survival for the first 8 years post transplant. At this point, transfer to adult units with non-compliance becomes a significant problem. Rejection is less of a problem than previously but infection is now a bigger issue--specifically tuberculosis (TB), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections with related complications. A wide variety of drugs are available for tailoring immunosuppression to minimise side-effects. CONCLUSION: It is possible to have a successful paediatric transplant programme in a developing country. However, to improve long-term outcomes certain issues need to be addressed, including reduction of nephrotoxic drugs and cardiovascular risk factors and providing successful adolescent to adult unit transition