Mediators of gram-positive septic shock

Septic shock can occur as a result of Gram-negative or Gram-positive infection and involves a complex interaction between bacterial factors and the host immune system producing a systemic inflammatory state that may progress to multiple organ failure and death. Gram-positive bacteria are increasingly becoming more prevalent especially Staphylococcus epidermidis in association with indwelling devices. Lipopolysaccaride (LPS) is the key Gram-negative component involved in this process, but it is not clear which components of Gram-positive bacteria are responsible for progression of this often fatal disease. The aim of this thesis was to investigate the effect of bacterial components on the immune systems. Lipid S, a short chain form of lipoteichoic acid (LTA) found to be excreted from bacteria during growth in culture medium was examined along with other Gram-positive cell wall components: LTA, peptidoglycan (PG) and wall teichoic acids (WTA) and LPS from Gram-negative bacteria. Lipid S, LTA, PG and LPS but not WTA all stimulated murine macrophages and cell lines to produce significant amounts of NO, TNF-a, IL-6 and IL-1 and would induce fever and tissue damage seen in inflammatory diseases. Lipid S proved to be the most potent out of the Gram-positive samples tested. IgG antibodies in patients serum were found to bind to and cross react with lipid S and LTA. Anti-inflammatory antibiotics, platelet activating factor (PAF), PAF receptor antagonists and monoclonal antibodies (mAbs) directed to LTA, CD14 and toll-like receptors were utilised to modulate cytokine and NO production. In cell culture the anti-LTA and the anti-CD14 mAbs failed to markedly attenuate the production of NO, TNF-a, IL-6 or IL-1, the anti-TLR4 antibody did greatly inhibit the ability of LPS to stimulate cytokine production but not lipid S. The tetracyclines proved to be the most effective compounds, many were active at low concentrations and showed efficacy to inhibit both lipid S and LPS stimulated macrophages to produce NO

Engineering geology of British rocks and soils : Lias Group

The report begins with an introduction and a detailed modern assessment of the geology of the Lias Group in terms of both stratigraphy and lithology. The modern lithostratigraphy is placed in the context of the old, and sometimes more familiar, usage. The next two chapters deal with the mineralogy of a suite of samples collected for the project, and an assessment of the nature and influence of weathering based on a detailed analysis of the Lias dataset held in the BGS National Geotechnical Properties Database. The following chapters cover geohazards associated with the Lias Group, and a brief overview of the wide variety of industrial applications for which the Lias is well known. The geotechnical database forms the basis of the penultimate chapter, geotechnical properties. The contents of the database are analysed, interpreted, presented in graphical form, and discussed in terms of statistical variation and in the light of likely engineering behaviour. The engineering geology of the Lias Group is discussed in the final chapter, borrowing from the preceding chapters. A comprehensive cited reference list and a bibliography are provided. In addition to the large number of technical data provided to BGS, a small data set has been generated by BGS laboratories, particularly in areas where the main database was deficient, and also in connection with associated BGS studies of the swelling and shrinkage properties of the Lias Group. The individual items of data making up the database are not attributed. However, the contribution of a wide range of consultancies, contractors, authorities, and individuals is acknowledged. It is hoped that this report will provide a source of useful information to a wide range of engineers, planners, scientists, and other interested parties concerned with Lias Group materials. It should be noted that whilst quantitative technical data are included in this report, these should not be used as a substitute for proper site investigation

Semiclassical interferences and catastrophes in the ionization of Rydberg atoms by half-cycle pulses

A multi-dimensional semiclassical description of excitation of a Rydberg electron by half-cycle pulses is developed and applied to the study of energy- and angle-resolved ionization spectra. Characteristic novel phenomena observable in these spectra such as interference oscillations and semiclassical glory and rainbow scattering are discussed and related to the underlying classical dynamics of the Rydberg electron. Modifications to the predictions of the impulse approximation are examined that arise due to finite pulse durations

Development of selective, ultra-fast multiple co-sensitization to control dye loading in dye-sensitized solar cells

Enhancing the spectral response of dye-sensitized solar cells (DSC) is essential to increasing device efficiency and a key approach to achieve this is co-sensitization (i.e. the use of multiple dyes to absorb light from different parts of the solar spectrum). However, precise control of dye loading within DSC mesoporous metal oxide photo-anodes is non-trivial especially for very rapid processing (minutes). This is further complicated by dyes having very different partition (Kd) and molar extinction (ε) coefficients which strongly influence dye uptake and spectral response, respectively. Here, we present a highly versatile, ultra-fast (ca. 5 min) desorption and re-dyeing method for dye-sensitized solar cells which can be used to precisely control dye loading in photo-electrode films. This method has been successfully applied to re-dye, partially desorb and re-dye and selectively desorb and re-dye photo-electrodes using examples of a Ru-bipy dye (N719) and also organic dyes (SQ1 and D149) giving η up to 8.1% for a device containing the organic dye D149 and re-dyed with the Ru dye N719. The paper also illustrates how this method can be used to rapidly screen large numbers of dyes (and/or dye combinations) and also illustrates how it can also be used to selectively study dye loading

Retrospective evaluation of foot-and-mouth disease vaccineeffectiveness in Turkey

AbstractFoot-and-mouth disease (FMD) is present in much of Turkey and its control is largely based on vaccination. The arrival of the FMD Asia-1 serotype in Turkey in 2011 caused particular concern, spreading rapidly westwards across the country towards the FMD free European Union. With no prior natural immunity, control of spread would rely heavily on vaccination.Unlike human vaccines, field protection is rarely evaluated directly for FMD vaccines. Between September 2011 and July 2012 we performed four retrospective outbreak investigations to assess the vaccine effectiveness (VE) of FMD Asia-1 vaccines in Turkey. Vaccine effectiveness is defined as the reduction in risk in vaccinated compared to unvaccinated individuals with similar virus exposure in the field.The four investigations included 12 villages and 1230 cattle >4 months of age. One investigation assessed the FMD Asia-1 Shamir vaccine, the other three evaluated the recently introduced FMD Asia-1 TUR 11 vaccine made using a field isolate of the FMD Asia-1 Sindh-08 lineage that had recently entered Turkey.After adjustment for confounding, the TUR 11 vaccine provided moderate protection against both clinical disease VE=69% [95% CI: 50%–81%] and infection VE=63% [95% CI: 29%–81%]. However, protection was variable with some herds with high vaccine coverage still experiencing high disease incidence. Some of this variability will be the result of the variation in virus challenge and immunity that occurs under field conditions.In the outbreak investigated there was no evidence that the Asia-1 Shamir vaccine provided adequate protection against clinical FMD with an incidence of 89% in single vaccinated cattle and 69% in those vaccinated two to five times.Based on these effectiveness estimates, vaccination alone is unlikely to produce the high levels of herd immunity needed to control FMD without additional control measures

High resolution study of the spatial distributions of abyssal fishes by autonomous underwater vehicle

On abyssal plains, demersal fish are believed to play an important role in transferring energy across the seafloor and between the pelagic and benthic realms. However, little is known about their spatial distributions, making it difficult to quantify their ecological significance. To address this, we employed an autonomous underwater vehicle to conduct an exceptionally large photographic survey of fish distributions on the Porcupine Abyssal Plain (NE Atlantic, 4850?m water depth) encompassing two spatial scales (1–10?km2) on and adjacent to a small abyssal hill (240?m elevation). The spatial distributions of the total fish fauna and that of the two dominant morphotypes (Coryphaenoides sp. 1 and C. profundicolus) appeared to be random, a result contrary to common expectation but consistent with previous predictions for these fishes. We estimated total fish density on the abyssal plain to be 723 individuals km?2 (95% CI: 601–844). This estimate is higher, and likely more precise, than prior estimates from trawl catch and baited camera techniques (152 and 188 individuals km?2 respectively). We detected no significant difference in fish density between abyssal hill and plain, nor did we detect any evidence for the existence of fish aggregations at any spatial scale assessed