Construction and testing of self-drilled soil nails

Current standards and best practice guidance recognise that testing of self-drilled hollow bar soil nails can be problematic as conventional packers and debonded lengths cannot be constructed. As a result, this causes difficulty in testing and confirming the ultimate bond resistance within the passive zone of a soil-nailed slope, and thus the design soil nail lengths. This paper provides a summary and review of the various testing procedures adopted for a soil nail construction project in Scotland. The practical design considerations, and their validation through the installation and testing of 49 sacrificial test nails, are detailed. The construction issues associated with the nail installation and testing are also outlined and discussed in light of the results obtained using different testing approaches. The aim of this case study is to report on the experiences with installation and testing of hollow bar soil nails. The objectives are to develop an initial data base of available soil–grout bond strength of hollow bar soil nails based on the several practical installation procedures used in this project and to establish areas for improvement of installation, testing and quality control in order to perform comparable pullout tests on self-drilled hollow bar soil nails. </jats:p

Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity.

BackgroundIn humans, inorganic arsenic (iAs) is metabolized to methylated arsenical species in a multistep process mainly mediated by arsenic (+3 oxidation state) methyltransferase (AS3MT). Among these metabolites is monomethylarsonous acid (MMAIII), the most toxic arsenic species. A recent study in As3mt-knockout mice suggests that unidentified methyltransferases could be involved in alternative iAs methylation pathways. We found that yeast deletion mutants lacking MTQ2 were highly resistant to iAs exposure. The human ortholog of the yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1), encoding a putative methyltransferase.ObjectiveWe investigated the potential role of N6AMT1 in arsenic-induced toxicity.MethodsWe measured and compared the cytotoxicity induced by arsenicals and their metabolic profiles using inductively coupled plasma-mass spectrometry in UROtsa human urothelial cells with enhanced N6AMT1 expression and UROtsa vector control cells treated with different concentrations of either iAsIII or MMAIII.ResultsN6AMT1 was able to convert MMAIII to the less toxic dimethylarsonic acid (DMA) when overexpressed in UROtsa cells. The enhanced expression of N6AMT1 in UROtsa cells decreased cytotoxicity of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at variable levels, although at levels lower than those of AS3MT, supporting a potential participation in arsenic metabolism in vivo.ConclusionsConsidering that MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a significant role in determining susceptibility to arsenic toxicity and carcinogenicity because of its specific activity in methylating MMAIII to DMA and other unknown mechanisms

Why is spirometry underused in the diagnosis of the breathless patient: a qualitative study

BackgroundUse of spirometry is essential for the accurate diagnosis of respiratory disease but it is underused in both primary and specialist care. In the current study, we have explored the reasons for this underuse.MethodsFive separate focus groups were undertaken with final year medical undergraduates, junior hospital doctors, general practitioners (GPs) and specialist trainees in respiratory medicine. The participants were not told prior to the session that we were specifically interested in their views about spirometry but discussion was moderated to elicit their approaches to the diagnosis of a breathless patient, their use of investigations and their learning preferences.ResultsUndergraduates and junior doctors rarely had a systematic approach towards the breathless patient and tended, unless prompted, to focus on the emergency room situation rather than on patients with longer term causes of breathlessness. Whilst their theoretical knowledge embraced the possibility of a non-respiratory cause for breathlessness, neither undergraduates nor junior doctors spontaneously mentioned the use of spirometry in the diagnosis of respiratory disease. When prompted they cited lack of familiarity with the use and location of equipment, and lack of encouragement to use it as being major barriers to utilization. In contrast, GPs and specialist respiratory trainees were enthusiastic about its use and perceived spirometry as a core element of the diagnostic workup.ConclusionsMore explicit training is needed regarding the role of spirometry in the diagnosis and management of those with lung disease and this necessitates both practical experience and training in interpretation of the data. However, formal teaching is likely to be undermined in practice, if the concept is not strongly promoted by the senior staff who act as role models and trainers

Comparison of a web-based package with tutor-based methods of teaching respiratory medicine: subjective and objective evaluations

BackgroundRespiratory disease is a major cause of morbidity and mortality not only in the United Kingdom, but globally. A good understanding of respiratory disease and its treatment is essential for all medical graduates. As a result of changes in clinical practice, patients with some common respiratory illnesses are less often admitted to hospital, restricting the experience available to undergraduate students. Combined with a potential shortage of clinical teachers, this means that new methods of teaching need to be developed and appraised. The aim of this study was to establish whether a web-based package on the diagnosis of respiratory disease would be as effective and as acceptable to final year medical students as tutor-led methods of teaching the same material.Methods137 out of 315 final year undergraduate students in a single medical school volunteered to take part. Each received up to two hours of tutor-lead interactive, tutor-lead didactic or electronic, Web-based teaching on the accurate diagnosis and management of respiratory disease. Post teaching performance was assessed by multiple true/false questions and data interpretation exercises, whilst students' teaching preferences were assessed by questionnaire.ResultsDespite a high knowledge baseline before the study, there was a small, but statistically significant increase in knowledge score after all forms of teaching. Similarly, data interpretation skills improved in all groups, irrespective of teaching format, Although paradoxically most students expressed a preference for interactive tutor-lead teaching, spirometry interpretation in those receiving web-based teaching improved significantly more [p = 0.041] than in those in the interactive group.ConclusionWeb-based teaching is at least as good as other teaching formats, but we need to overcome students' reluctance to engage with this teaching method

Issues of Processing and Multiple Testing of SELDI-TOF MS Proteomic Data

A new data filtering method for SELDI-TOF MS proteomic spectra data is described. We examined technical repeats (2 per subject) of intensity versus m/z (mass/charge) of bone marrow cell lysate for two groups of childhood leukemia patients: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As others have noted, the type of data processing as well as experimental variability can have a disproportionate impact on the list of interesting proteins (see Baggerly et al. (2004)). We propose a list of processing and multiple testing techniques to correct for 1) background drift; 2) filtering using smooth regression and cross-validated bandwidth selection; 3) peak finding; and 4) methods to correct for multiple testing (van der Laan et al. (2005)). The result is a list of proteins (indexed by m/z) where average expression is significantly different among disease (or treatment, etc.) groups. The procedures are intended to provide a sensible and statistically driven algorithm, which we argue provides a list of proteins that have a significant difference in expression. Given no sources of unmeasured bias (such as confounding of experimental conditions with disease status), proteins found to be statistically significant using this technique have a low probability of being false positives

The Flavoring Agent Dihydrocoumarin Reverses Epigenetic Silencing and Inhibits Sirtuin Deacetylases

Sirtuins are a family of phylogenetically conserved nicotinamide adenine dinucleotide-dependent deacetylases that have a firmly established role in aging. Using a simple Saccharomyces cerevisiae yeast heterochromatic derepression assay, we tested a number of environmental chemicals to address the possibility that humans are exposed to sirtuin inhibitors. Here we show that dihydrocoumarin (DHC), a compound found in Melilotus officinalis (sweet clover) that is commonly added to food and cosmetics, disrupted heterochromatic silencing and inhibited yeast Sir2p as well as human SIRT1 deacetylase activity. DHC exposure in the human TK6 lymphoblastoid cell line also caused concentration-dependent increases in p53 acetylation and cytotoxicity. Flow cytometric analysis to detect annexin V binding to phosphatidylserine demonstrated that DHC increased apoptosis more than 3-fold over controls. Thus, DHC inhibits both yeast Sir2p and human SIRT1 deacetylases and increases p53 acetylation and apoptosis, a phenotype associated with senescence and aging. These findings demonstrate that humans are potentially exposed to epigenetic toxicants that inhibit sirtuin deacetylases