Access and safety at geological sites: a manual for landowners, quarry operators and the geological visitor

Mineral Industry Research Organisation: Aggregates Sustainability Levy Fun

Settlement Of Oyster (Crassostrea-Virginica) Larvae - Effects Of Water-Flow And A Water-Soluble Chemical Cue

Although previous evidence indicates that larvae of benthic marine invertebrates can respond to waterborne cues in still water, the importance of waterborne cues in mediating natural settlement out of flowing water has been questioned. Here, we summarize the results of flume experiments demonstrating enhanced settlement of oyster larvae in small target wells (circles of 7-cm diam) with the release of a waterborne settlement cue compared to identical substrates without the cue. In concurrent still-water experiments, more oyster larvae settled in solutions of waterborne cue than in seawater controls. Velocity and electrochemical measurements of a conservative tracer verified that at low flow velocities (2 and 6 cm s(-1)) with U* value

Evaluation of demand in a rural English hospital emergency department

The purpose of this article is to analyse the patient demand placed on a rural district general hospital (DGH) emergency department within the context of the Purpose, Process, People (PPP) framework used in the private sector. This analysis was undertaken to inform wider evaluation of the implementation of the enterprise culture—the NHS policy to adopt private sector best practice to produce resource use, quality and efficiency improvements. The article concludes with a view that the PPP framework provides methods of calculating the level of discharge necessary to meet the four-hour wait target. Data describing the characteristics and patterns of attending patients can be used to develop an emergency department’s processes and people to achieve its time-based target

Uncertainty Surrounding Projections of the Long-Term Impact of Ivermectin Treatment on Human Onchocerciasis

BackgroundRecent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment.Methodology/principal findingsWe modify a deterministic age- and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution.Conclusions/significanceThere is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities

Corrigendum: Solar cycles or random processes? Evaluating solar variability in Holocene climate records

This is the final version of the article. Available from Springer Nature via the DOI in this record.The article to which this is the corrigendum is in ORE at http://hdl.handle.net/10871/21766A coding error in the Monte Carlo procedure for the determination of critical values in running correlation analysis (presented in Supplementary Data S8) has been brought to the attention of the authors.[...

Liminal Roles as a Source of Creative Agency in Management: The Case of Knowledge-Sharing Communities

Studies suggest that the experience of liminality – of being in an ambiguous, ‘betwixt and between’ position – has creative potential for organizations. We contribute to theory on the link between liminality and creative agency through a study of the coordinators of ‘knowledge-sharing communities’; one of the latest examples of a ‘neo-bureaucratic’ practice that seeks to elicit innovative responses from employees while intensifying control by the organization. Through a role-centred perspective, our study found that both the structural and interpretive aspects of coordinators’ role enactments promoted a degree of creative agency. ‘Front-stage’ and ‘back-stage’ activities were developed to meet the divergent expectations posed by senior management and community members, and the ambiguity of their roles prompted an array of different role interpretations. Our findings contribute to theory by showing how the link between liminality and creative agency is not confined to roles and spaces (consultancy work, professional expertise) that are positioned across organizational boundaries, or free from norms and expectations, but may also apply to roles that are ambiguously situated within organizational contexts and which are subject to divergent expectations. This shows how neo-bureaucratic forms may be both reproduced and renewed through the creative responses of individual managers

Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis

BACKGROUND: Multiple blood transcriptional signatures have been proposed for identification of active and incipient tuberculosis. We aimed to compare the performance of systematically identified candidate signatures for incipient tuberculosis and to benchmark these against WHO targets. METHODS: We did a systematic review and individual participant data meta-analysis. We searched Medline and Embase for candidate whole blood mRNA signatures discovered with the primary objective of diagnosis of active or incipient tuberculosis, compared with controls who were healthy or had latent tuberculosis infection. We tested the performance of eligible signatures in whole blood transcriptomic datasets, in which sampling before tuberculosis diagnosis was done and time to disease was available. Culture-confirmed and clinically or radiologically diagnosed pulmonary or extrapulmonary tuberculosis cases were included. Non-progressor (individuals who remained tuberculosis-free during follow-up) samples with less than 6 months of follow-up from the date of sample collection were excluded, as were participants with prevalent tuberculosis and those who received preventive therapy. Scores were calculated for candidate signatures for each participant in the pooled dataset. Receiver operating characteristic curves, sensitivities, and specificities were examined using prespecified intervals to tuberculosis (<3 months, <6 months, <1 year, and <2 years) from sample collection. This study is registered with PROSPERO, number CRD42019135618. RESULTS: We tested 17 candidate mRNA signatures in a pooled dataset from four eligible studies comprising 1126 samples. This dataset included 183 samples from 127 incipient tuberculosis cases in South Africa, Ethiopia, The Gambia, and the UK. Eight signatures (comprising 1-25 transcripts) that predominantly reflect interferon and tumour necrosis factor-inducible gene expression, had equivalent diagnostic accuracy for incipient tuberculosis over a 2-year period with areas under the receiver operating characteristic curves ranging from 0·70 (95% CI 0·64-0·76) to 0·77 (0·71-0·82). The sensitivity of all eight signatures declined with increasing disease-free time interval. Using a threshold derived from two SDs above the mean of uninfected controls to prioritise specificity and positive-predictive value, the eight signatures achieved sensitivities of 24·7-39·9% over 24 months and of 47·1-81·0% over 3 months, with corresponding specificities of more than 90%. Based on pre-test probability of 2%, the eight signatures achieved positive-predictive values ranging from 6·8-9·4% over 24 months and 11·2-14·4% over 3 months. When using biomarker thresholds maximising sensitivity and specificity with equal weighting to both, no signature met the minimum WHO target product profile parameters for incipient tuberculosis biomarkers over a 2-year period. INTERPRETATION: Blood transcriptional biomarkers reflect short-term risk of tuberculosis and only exceed WHO benchmarks if applied to 3-6-month intervals. Serial testing among carefully selected target groups might be required for optimal implementation of these biomarkers. FUNDING: Wellcome Trust and National Institute for Health Research

Embedding patient and public involvement: managing tacit and explicit expectations

Background: Evidencing well-planned and implemented patient and public involvement (PPI) in a research project is increasingly required in funding bids and dissemination activities. There is a tacit expectation that involving people with experience of the condition under study will improve the integrity and quality of the research. This expectation remains largely unproblematised and unchallenged. Objective: To critically evaluate the implementation of PPI activity, including co-research in a programme of research exploring ways to enhance the independence of people with dementia. Design: Using critical cases we make visible and explicate theoretical and moral challenges of PPI. Results: Case 1 explores the challenges of undertaking multiple PPI roles in the same study making explicit different responsibilities of being a co-applicant, PPI advisory member and a co-researcher. Case 2 explores tensions which arose when working with carer co-researchers during data collection; here the co-researcher’s wish to offer support and advice to research participants, a moral imperative, was in conflict with assumptions about the role of the objective interviewer. Case 3 defines and examines co-research data coding and interpretation activities undertaken with people with dementia; reporting the theoretical outputs of the activity and questioning whether this was co-researcher analysis or PPI validation. Conclusion: PPI activity can empower individual PPI volunteers and improve relevance and quality of research but it is a complex activity which is socially constructed in flexible ways with variable outcomes. It cannot be assumed to be simple or universal panacea for increasing the relevance and accessibility of research to the public

Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study.

BACKGROUND: Blood transcriptional signatures are candidates for non-sputum triage or confirmatory tests of tuberculosis. Prospective head-to-head comparisons of their diagnostic accuracy in real-world settings are necessary to assess their clinical use. We aimed to compare the diagnostic accuracy of candidate transcriptional signatures identified by systematic review, in a setting with a high burden of tuberculosis and HIV. METHODS: We did a prospective observational study nested within a diagnostic accuracy study of sputum Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) tests for pulmonary tuberculosis. We recruited consecutive symptomatic adults aged 18 years or older self-presenting to a tuberculosis clinic in Cape Town, South Africa. Participants provided blood for RNA sequencing, and sputum samples for liquid culture and molecular testing using Xpert and Ultra. We assessed the diagnostic accuracy of candidate blood transcriptional signatures for active tuberculosis (including those intended to distinguish active tuberculosis from other diseases) identified by systematic review, compared with culture or Xpert MTB/RIF positivity as the standard reference. In our primary analysis, patients with tuberculosis were defined as those with either a positive liquid culture or Xpert result. Patients with missing blood RNA or sputum results were excluded. Our primary objective was to benchmark the diagnostic accuracy of candidate transcriptional signatures against the WHO target product profile (TPP) for a tuberculosis triage test. FINDINGS: Between Feb 12, 2016, and July 18, 2017, we obtained paired sputum and RNA sequencing data from 181 participants, 54 (30%) of whom had confirmed pulmonary tuberculosis. Of 27 eligible signatures identified by systematic review, four achieved the highest diagnostic accuracy with similar area under the receiver operating characteristic curves (Sweeney3: 90·6% [95% CI 85·6-95·6]; Kaforou25: 86·9% [80·9-92·9]; Roe3: 86·9% [80·3-93·5]; and BATF2: 86·8% [80·6-93·1]), independent of age, sex, HIV status, previous tuberculosis, or sputum smear result. At test thresholds that gave 70% specificity (the minimum WHO TPP specificity for a triage test), these four signatures achieved sensitivities between 83·3% (95% CI 71·3-91·0) and 90·7% (80·1-96·0). No signature met the optimum criteria, of 95% sensitivity and 80% specificity proposed by WHO for a triage test, or the minimum criteria (of 65% sensitivity and 98% specificity) for a confirmatory test, but all four correctly identified Ultra-positive, culture-negative patients. INTERPRETATION: Selected blood transcriptional signatures met the minimum WHO benchmarks for a tuberculosis triage test but not for a confirmatory test. Further development of the signatures is warranted to investigate their possible effects on clinical and health economic outcomes as part of a triage strategy, or when used as add-on confirmatory test in conjunction with the highly sensitive Ultra test for Mycobacterium tuberculosis DNA. FUNDING: Royal Society Newton Advanced Fellowship, Wellcome Trust, National Institute of Health Research, and UK Medical Research Council