Triassic stratigraphy and sedimentology in central England

The Triassic rocks of Central England consist of three major stratigraphic units: Sherwood Sandstone Group, Mercia Mudstone Group, and Penarth Group. The lower part of the Sherwood Sandstone Group represented by the Kidderminster, Cannock Chase, and Polesworth Formations represents pebbly braided river deposits carried by a major fluvial system flowing to the North-Northwest. The upper part of the Sherwood Sandstone Group includes the Wildmoor and Bromsgrove Sandstone Formations, the deposits of a sandy alluvial system. The Mercia Mudstone Group represents quiet-water deposits of marginal palya type which were subjected to occasional marine flooding. The overlying Penarth Group represent shallow marine and lagoonal environment associated with the Rhaetian marine transgression. The mineralogy of the Triassic sandstones indicates that the main source was from medium to low rank metamorphic rocks with additional supplies from igneous and metamorphic rocks. The study of size-composition trends shows that the climate was semiarid in early Triassic time and became more humid later. The Triassic sandstones show a variety of diagenetic features typical of continental red beds; these include: 1. the dissolution of unstable ferromagnesian silicates, 2. the replacement of detrital grains by clay, 3. the pseudomorphism of biotite by haematite, and 4. the formation of a suite of authigenic minerals including quartz, illite, mixed-layer illite-montmorillonite, kaolinite, k-feldspar, haematite, titanium oxide and later carbonate cement. Palaeomagnetic studies of selected samples show that the magnetization is muticomponent with the various components being carried by different textural phases of haematite.

The Evaluation of health and safety auditing systems

The specific objective of the research was to evaluate proprietary audit systems. Proprietary audit systems comprise question sets containing approximately 500 questions dealing with selected aspects of health and safety management. Each question is allotted a number of points and an organisation seeks to judge its health and safety performance by the overall score achieved in the audit. Initially it was considered that the evaluation method might involve comparing the proprietary audit scores with other methods of measuring safety performance. However, what appeared to be missing in the first instance was information that organisations could use to compare the contrast question set content against their own needs. A technique was developed using the computer database FileMaker Pro. This enables questions in an audit to be sorted into categories using a process of searching for key words. Questions that are not categorised by word searching can be identified and sorted manually. The process can be completed in 2-3 hours which is considerably faster than manual categorisation of questions which typically takes about 10 days. The technique was used to compare and contrast three proprietary audits: ISRS, CHASE and QSA. Differences and similarities between these audits were successfully identified. It was concluded that in general proprietary audits need to focus to a greater extent on identifying strengths and weaknesses in occupational health and safety management systems. To do this requires the inclusion of more probing questions which consider whether risk control measures are likely to be successful.

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Sustainability in higher education:stories and strategies for transformation

Book review of Peggy F. Bartlett and Geoffrey W. Chase (eds.), Sustainability in Higher Education: Stories and Strategies for Transformation