Towards effective conservation of the Pilbara Early Life Sites as a multifunctional landscape: exploring lessons from national and international baest practice

Geoconservation - the practice of conserving geological features, from the landscape scale all the way down to the individual crystal scale - is growing in importance, as sites of international heritage value around the world face increasing pressure from human activities. A collection of geological sites that urgently require more effective protection is in the Pilbara region of Western Australia, where ancient rocks - up to 3.5 billion years old - that are extremely well preserved contain fossil stromatolites and microfossils that represent the earliest convincing evidence of life on Earth (henceforth Pilbara Early Life Sites). In addition, the Pilbara Early Life Sites contain some of the best evidence of the environments where life gained a foothold on early Earth, and even provide clues as to how life may have begun. Indeed, these sites help to paint a picture of the early Earth, when small volcanic islands rising out from the ocean formed the first exposed landmasses and provided heat, minerals, and chemical energy for primitive life to form and grow into communities that spread across shallow pools on land, occupied hydrothermal veins, and adapted to shallow marine habitats. This information is key not only for understanding the origin and evolution of life on Earth, but to help develop strategies for where to search for life on Mars and elsewhere in the solar system and is used by space agencies from around the world in mission planning. The excellent preservation of the Pilbara Early Life Sites is globally extremely rare. Such excellent preservation is key to understanding the processes of past life, and therefore using these sites as a teaching resource. The Pilbara Early Life Sites are small, isolated outcrops and are therefore vulnerable to irretrievable loss through illegal sample collection from unknown sources. Ever since the Pilbara Early Life Sites were first described by Walter et al. (1980) and by Lowe (1980), illegal collection of valuable outcrop material has been an issue of real concern. Because the key sites where excellent preservation of textures and the relationships between the traces of life and their habitats are so small (10m2) and isolated, and because the value of sites is critically dependent on being able to view the fossils in-situ, within their relevant context where their relationship to surrounding geology can be viewed, the illegal removal of material is a major loss of both important scientific knowledge and universal heritage value. There have been several attempts to conserve the Pilbara Early Life Sites, however none of these have succeeded in the long term. This thesis investigates whether the current method of protection is adequate, identifies and evaluates a range of approaches for conservation moving forward, and develops a roadmap toward more effective, meaningful conservation of the Pilbara Early Life Sites. This roadmap strives to ensure the conservation and management of the Pilbara Early Life Sites does not negatively impact local industries, communities, and future scientific research. Rather, this roadmap will facilitate an enhanced public understanding of the sites, allow for education of future researchers, conservation practitioners, and the public, as well as promote responsible scientific research through better working partnerships with other stakeholders. This thesis has employed a mixed-methods approach, wherein qualitative data was collected, and both qualitative and quantitative analysis techniques were used. These collection and analysis techniques included interviews, literature review, PESTLE analysis, SWOT analysis, and application of the Brocx and Semeniuk ‘Geoheritage Toolkit’. The analyses show that the current method of conservation is inadequate, and that alternative methods of conservation and management strategies are required to ensure the future protection of the Pilbara Early Life Sites. These will be informed by best national and international practice. The recommend protection is National Heritage Listing. Due to the extended timeframe and practical considerations of implementing National Heritage Listing, additional conservation measures are also explored

Breaking the shackles: the continuing fight against censorship and spin 2008

This is the 2008 edition of the Alliance\u27s annual report into the state of press freedom in Australia, and reports some promising developments over the past twelve months

Learning from practice: how East Lancashire hospitals' pharmacy service has embraced information technology

The ethos of the pharmacy service at East Lancashire Hospitals NHS Trust (ELHT) could be described as ‘let’s make things better’. We have a history of innovation involving technology and people; one without the other does not work but together they are synergistic. The Trust currently does not have an electronic patient record (ePR) or electronic prescribing and medicines administration (ePMA), although we do have electronic prescribing for chemotherapy. However, like all Trusts, we have many electronic systems which offer interoperability, or can support making it easier for the pharmacy team to do a good job. This article describes the many fronts we have worked on over the last ten plus years. Taken individually, the elements cannot be considered as revolutionary; together, they have helped us develop and deliver the safe, personal and effective pharmacy service that we call dedicated ward pharmacy

Consistency and interpretation of changes in millimeter-scale cortical intrinsic curvature across three independent datasets in schizophrenia.

Several studies have sought to test the neurodevelopmental hypothesis of schizophrenia through analysis of cortical gyrification. However, to date, results have been inconsistent. A possible reason for this is that gyrification measures at the centimeter scale may be insensitive to subtle morphological changes at smaller scales. The lack of consistency in such studies may impede further interpretation of cortical morphology as an aid to understanding the etiology of schizophrenia. In this study we developed a new approach, examining whether millimeter-scale measures of cortical curvature are sensitive to changes in fundamental geometric properties of the cortical surface in schizophrenia. We determined and compared millimeter-scale and centimeter-scale curvature in three separate case-control studies; specifically two adult groups and one adolescent group. The datasets were of different sizes, with different ages and gender-spreads. The results clearly show that millimeter-scale intrinsic curvature measures were more robust and consistent in identifying reduced gyrification in patients across all three datasets. To further interpret this finding we quantified the ratio of expansion in the upper and lower cortical layers. The results suggest that reduced gyrification in schizophrenia is driven by a reduction in the expansion of upper cortical layers. This may plausibly be related to a reduction in short-range connectivity

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke--Blood Pressure) randomised controlled trial.

OBJECTIVE: To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. DESIGN: Open label randomised controlled trial. SETTING: 99 general practices in England, with participants recruited in 2009-11. PARTICIPANTS: People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. INTERVENTIONS: Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. MAIN OUTCOME MEASURE: Change in systolic blood pressure between baseline and 12 months. RESULTS: 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). CONCLUSIONS: Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure.Trial registration Current Controlled Trials ISRCTN29062286.This report is independent research funded by the National Institute for Health Research (Stroke Prevention in Primary Care, Programme Grant for Applied Research, RP-PG-0606-1153), and by an NIHR Professorship (Prof McManus). FDRH is part funded as Director of the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR), Theme Leader of the NIHR Oxford Biomedical Research Centre (BRC), and Director of the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS. The study sponsor was the University of Birmingham. The study funder and sponsor had no role in the study design, collection, analysis or interpretation of data, in the writing of the report, or in the decision to submit to publication. The researchers are independent of the funders.This is the final version of the article. It first appeared from the BMJ Publishing Group via http://dx.doi.org/10.1136/bmj.i70

Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A.

OBJECTIVES: To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. DESIGN: Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses to antigen 85, overlapping peptides of antigen 85A and tuberculin purified protein derivative (PPD) detected by ex vivo interferon-gamma (IFN-gamma) ELISpot assay and flow cytometry. RESULTS AND CONCLUSIONS: BCG revaccination (BCG-BCG) was well tolerated, and boosting of pre-existing PPD-specific T cell responses was observed. However, when these results were compared with data from a previous clinical trial, where BCG was boosted with MVA85A (BCG-MVA85A), MVA85A induced significantly higher levels (>2-fold) of antigen 85-specific CD4+ T cells (both antigen and peptide pool responses) than boosting with BCG, up to 52 weeks post-vaccination (p = 0.009). To identify antigen 85A-specific CD8+ T cells that were not detectable by ex vivo ELISpot and flow cytometry, dendritic cells (DC) were used to amplify CD8+ T cells from PBMC samples. We observed low, but detectable levels of antigen 85A-specific CD8+ T cells producing IFNgamma (1.5% of total CD8 population) in the BCG primed subjects after BCG boosting in 1 (20%) of 5 subjects. In contrast, in BCG-MVA85A vaccinated subjects, high levels of antigen 85A-specific CD8+ T cells (up to 14% total CD8 population) were observed after boosting with MVA85A, in 4 (50%) of 8 subjects evaluated. In conclusion, revaccination with BCG resulted in modest boosting of pre-existing immune responses to PPD and antigen 85, but vaccination with BCG-MVA85A induced a significantly higher response to antigen 85 and generated a higher frequency of antigen 85A-specific CD8+ T cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT00654316 NCT00427830

"BioSandwich", a homology-based assembly method using a library of standard parts

This Request for Comments (RFC) describes a strategy for using homology-based assembly methods to assemble parts from a library in any order

Cost-effectiveness analysis of different systolic blood pressure targets for people with a history of stroke or transient ischaemic attack: Economic analysis of the PAST-BP study.

BACKGROUND: The PAST-BP trial found that using a lower systolic blood pressure target (<130 mmHg or lower versus <140 mmHg) in a primary care population with prevalent cerebrovascular disease was associated with a small additional reduction in blood pressure (2.9 mmHg). OBJECTIVES: To determine the cost effectiveness of an intensive systolic blood pressure target (<130 mmHg or lower) compared with a standard target (<140 mmHg) in people with a history of stroke or transient ischaemic attack on general practice stroke/transient ischaemic attack registers in England. METHODS: A Markov model with a one-year time cycle and a 30-year time horizon was used to estimate the cost per quality-adjusted life year of an intensive target versus a standard target. Individual patient level data were used from the PAST-BP trial with regard to change in blood pressure and numbers of primary care consultations over a 12-month period. Published sources were used to estimate life expectancy and risks of cardiovascular events and their associated costs and utilities. RESULTS: In the base-case results, aiming for an intensive blood pressure target was dominant, with the incremental lifetime costs being £169 lower per patient than for the standard blood pressure target with a 0.08 quality-adjusted life year gain. This was robust to sensitivity analyses, unless intensive blood pressure lowering reduced quality of life by 2% or more. CONCLUSION: Aiming for a systolic blood pressure target of <130 mmHg or lower is cost effective in people who have had a stroke/transient ischaemic attack in the community, but it is difficult to separate out the impact of the lower target from the impact of more active management of blood pressure.National Institute for Health Research (Grant ID: RP-PG-0606-1153)This is the author accepted manuscript. The final version is available from SAGE Publications via http://dx.doi.org/10.1177/204748731665198

Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

PURPOSE: A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. METHODS: Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. RESULTS: There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. CONCLUSION: A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected

Differential tangential expansion as a mechanism for cortical gyrification.

Gyrification, the developmental buckling of the cortex, is not a random process-the forces that mediate expansion do so in such a way as to generate consistent patterns of folds across individuals and even species. Although the origin of these forces is unknown, some theories have suggested that they may be related to external cortical factors such as axonal tension. Here, we investigate an alternative hypothesis, namely, whether the differential tangential expansion of the cortex alone can account for the degree and pattern-specificity of gyrification. Using intrinsic curvature as a measure of differential expansion, we initially explored whether this parameter and the local gyrification index (used to quantify the degree of gyrification) varied in a regional-specific pattern across the cortical surface in a manner that was replicable across independent datasets of neurotypicals. Having confirmed this consistency, we further demonstrated that within each dataset, the degree of intrinsic curvature of the cortex was predictive of the degree of cortical folding at a global and regional level. We conclude that differential expansion is a plausible primary mechanism for gyrification, and propose that this perspective offers a compelling mechanistic account of the co-localization of cytoarchitecture and cortical folds