The impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependent

Streptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism

Soil sustainability in organic agricultural production

Traditionally, the assessment of soil sustainability and the potential impact of cultivation are based upon the application of chemical procedures. In the absence of a biological context, these measurements offer little in understanding longterm changes in soil husbandry. Detailed microcosm investigations were applied as a predictive tool for management change. The microcosms were designed with homogenised soils treated with organic amendments. Key soil functional relationships were quantified using stable isotope techniques, biochemical measurements and traditional approaches

Briefing and Reframing

The ability to reframe a problematic situation in new and interesting ways is widely seen as one of the key characteristics of design thinking, and as one that would lend itself to application beyond the traditional design professions. In this paper we study how experienced designers have professionalised the crucial art of frame communication and new frame adoption with their clients. During briefing, professional designers elicit a client's frame, re- frame it to be more workable and desirable, and reflect it back. The iterative exchange at the start of a project is loaded with framing and reframing episodes. In this study fifteen highly experienced visual communications designers were interviewed and asked about briefing activities for what they deemed to be 'typical' and 'innovative' projects. This yielded rich descriptions of strategies that these professional designers used to enable reframing of the situation with non-designers, insights into possible difficulties and patterns of briefing practices. The paper concludes with an overview of activities and strategies that help with framing and reframing, as well as modes of communication that assist with sharing frames

Using phenology of eucalypts to determine environmental watering regimes for the River Murray floodplain South Australia

Trees on the River Murray floodplain in South Australia, particularly river red gum and black box (Myrtaceae: Eucalyptus camaldulensis, E. largiflorens), are increasingly water-stressed as the period since effective overbank flows extends to six years. As a result of declining health and dry conditions, recruitment rates in these species are insufficient to maintain populations. This study examined phenological cycles to determine the potential for timing environmental flows to promote recruitment. Results indicate a relatively consistent pattern in river red gums, which would benefit from watering in summer (December-February) to reinforce bud set, flowering and germination during peak seed rain from aerial seed banks. Present environmental flow programs may not provide water to black box on elevated areas of the floodplain, but this species would benefit from watering to reinforce bud set and flowering either in summer (December- February) or winter (May-July), depending on the phenological cycle of the trees to be watered. The possibility of watering to support seedlings in autumn, following above-average rainfall in the previous spring, warrants more study.Anne Jensen, Keith Walker and David Pato

Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia

Objective: The authors systematically reviewed the literature on psychological approaches to treating the neuropsychiatric symptoms of dementia.Method: Reports of studies that examined effects of any therapy derived from a psychological approach that satisfied prespecified criteria were reviewed. Data were extracted, the quality of each study was rated, and an overall rating was given to each study by using the Oxford Centre for Evidence-Based Medicine criteria.Results: A total of 1,632 studies were identified, and 162 satisfied the inclusion criteria for the review. Specific types of psychoeducation for caregivers about managing neuropsychiatric symptoms were effective treatments whose benefits lasted for months, but other caregiver interventions were not. Behavioral management techniques that are centered on individual patients' behavior or on caregiver behavior had similar benefits, as did cognitive stimulation. Music therapy and Snoezelen, and possibly sensory stimulation, were useful during the treatment session but had no longer-term effects; interventions that changed the visual environment looked promising, but more research is needed.Conclusions: Only behavior management therapies, specific types of caregiver and residential care staff education, and possibly cognitive stimulation appear to have lasting effectiveness for the management of dementia-associated neuropsychiatric symptoms. Lack of evidence regarding other therapies is not evidence of lack of efficacy. Conclusions are limited because of the paucity of high-quality research ( only nine level-1 studies were identified). More high-quality investigation is needed

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey

AbstractDespite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course.Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas.Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection

Examining fault architecture and strain distribution using geospatial and geomechanical modelling: An example from the Qaidam basin, NE Tibet

The investigation of complex geological setting is still dominated by traditional geo-data collection and analytical techniques, e.g., stratigraphic logging, dip data measurements, structural ground mapping, seismic interpretation, balance section restoration, forward modelling, etc. Despite the advantages of improving our understanding in structural geometry and fault architecture, the geospatial modelling, applying computer-aided three-dimensional geometric design, visualization and interpretation, has rarely been applied to such complex geological setting. This study used the Lenghu fold-and-thrust belt (in Qaidam basin, NE Tibetan Plateau) to demonstrate that the application of geospatial and geomechanical modelling could improve our understanding and provide an effective technique for investigating the fault architecture and strain distribution. The three-dimensional configuration of the Lenghu fold-and-thrust belt was initially derived from traditional analysis techniques, such as regional stratigraphic logging, cross section construction, meso-scale ground mapping and landsat image interpretation. The high-resolution field data and landsat image were integrated to construct the geospatial model, which was subsequently used to quantitatively investigate the fault throw changes along the Lenghu thrust fault zone and to understand its control on the lateral structural variation. The geospatial model was then restored in three dimensions to reveal the kinematic evolution of the Lenghu fold-and-thrust belt. Geomechanical modelling, using a Mass-Spring algorithm, provided an effective three-dimensional tool for structural strain analysis, which was used to predict the strain distribution throughout the overall structure, e.g., normal faults with throws ranging from meters to tens of meters in the hanging-wall. The strain distribution predicted by geomechanical modelling was then validated by the natural normal faults in the hanging-wall. The high accordance between the strain prediction and statistics of natural normal faults demonstrates good applicability of geospatial and geomechanical modelling in the complex geological setting of the Lenghu fold-and-thrust belt. The geospatial models and geomechanical models, therefore, can provide a robust technique for analyzing and interpreting multi-source data within a three-dimensional environment. We anticipate that the application of three-dimensional geospatial modelling and geomechanical modelling, integrating both multi-source geologic data and three-dimensional analytical techniques, can provide an effective workflow for investigating the fault architecture and strain distribution at different scales (e.g., ranging from regional-to meso-scale)

Bringing genetics into primary care: findings from a national evaluation of pilots in England

Objectives: Developments in genetic knowledge and clinical applications are seen as rendering traditional modes of organizing genetics provision increasingly inappropriate. In common with a number of developed world countries the UK has sought to increase the role of primary care in delivering such services. However, efforts to reconfigure service delivery face multiple challenges associated with divergent policy objectives, organizational boundaries and professional cultures. This paper presents findings from an evaluation of an English initiative to integrate genetics into 'mainstream' clinical provision in the National Health Service. Methods: Qualitative research in 11 case-study sites focusing on attempts by pilots funded by the initiative to embed knowledge and provision within primary care illustrating barriers faced and the ways in which these were surmounted. Results: Lack of intrinsic interest in clinical genetics among primary care staff was compounded by national targets that focused their attention elsewhere and by service structures that rendered genetics a peripheral concern demanding minimal engagement. Established divisions between the commissioning of mainstream and specialist services, along with the pressures of shorter-term targets, impeded ongoing funding. Conclusions: More wide-ranging policy and organizational support is required if the aim of entrenching genetics knowledge and practice across the Health Service is to be realized

Measurements of Ultrasonic Scattering from Bulk Flaws of Complex Shape

The report summarizes the design and early results of scattering experiments on fl aw.s of complex shape. In close collaboration with the varied theoretical groups representing different inversion algorithms, a unique set of diffusion bonded samples have been designed. These samples contain a variety of irregular and multiple flaws whose scattering characteristics will be obtained in order to guide and evaluate developments of theoretical approaches and test specific theoretical predictions. The majority of these samples have been received an.d the measurements have begun. Results on selected samples are presented an.d compared with scattering from ellipsoidal voids. The measurements will include angular, frequency and time domain variations of the scattered signals made possible with a new ultrasonic data acquisition system

Are Wetland Regulations Cost Effective for Species Protection? A Case Study of Amphibian Metapopulations

Recent declines in amphibian populations have raised concern among conservation biologists, with habitat loss and degradation due to human activities among the leading causes. The most common policies used to protect the habitat of pond-breeding amphibians are wetland regulations that safeguard the wetland itself. However, many amphibians spend much of their adult lives foraging and over-wintering in upland habitats and exist as metapopulations with dispersal among ponds. With no consideration of lands in the dispersal matrix, wetland policies may be ineffective at protecting amphibians or other wetland species that disperse across the landscape. This paper examined the adequacy and cost effectiveness of alternative conservation policies and their corresponding land use patterns on the long-term persistence of pond-breeding amphibians in exurban landscapes. We used computer simulations to compare outcomes of wetland buffer policies and broader landscape wide conservation policies across a variety of landscape scenarios, and we conducted sensitivity analyses on the model\u27s species parameters in order to generalize our results to other wetland species. Results showed that, in the majority of human-dominated landscapes, some amount of dispersal matrix protection is necessary for long-term species persistence. However, in landscapes with extremely low-intensity land use (e.g., low-density residential housing) and high pond density, wetland buffer policies may be all that is required. It is not always more cost effective to protect core habitat over the dispersal matrix, a common conservation practice. Conservation costs that result from forgone residential, commercial, or agricultural activities can vary substantially but increase in a nonlinear manner regardless of land use zoning. There appears to be a threshold around an average habitat patch occupancy level of 80%, after which opportunity costs rise dramatically