Population sensitivity of acute flaccid paralysis and environmental surveillance for serotype 1 poliovirus in Pakistan: an observational study

Background To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation. Methods Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community. Results The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8–35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4–63.0), with significant variation in site-specific estimates (median varied from 33.3–79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2–98.7), assuming four samples per month for each site. Conclusions ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance

The impact of information, value-deliberation and group-based decision-making on values for ecosystem services:Integrating deliberative monetary valuation and storytelling

We thank the four anonymous referees whose comments substantially helped to improve this paper. We thank Anna Attlee and Althea Davies who helped to facilitate the research workshops; Anna Attlee also for helping to analyse the qualitative data. We thank all the participants of our study for their effort, and the Marine Conservation Society, the British Sub-Aqua Club and the Angling Trust for assisting with participant recruitment. This work was funded through the UK National Ecosystem Assessment Follow-On (Work Package 6: Shared, Plural and Cultural Values), funded by the UK Department of the Environment, Food and Rural Affairs (Defra), the Welsh Government, the UK Natural Environment Research Council (NERC), Economic and Social Research Council (ESRC), and Arts and Humanities Research Council (AHRC); additional funding was received from the Calouste Gulbenkian Foundation through the Marine Conservation Society. J.O. Kenter was also supported by the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no 315925 and K.N. Irvine by the Scottish Government Rural and Economic Sciences and Analytical Service (RESAS) Division.Peer reviewedPublisher PD

Teneurin Structures Are Composed of Ancient Bacterial Protein Domains

Pioneering bioinformatic analysis using sequence data revealed that teneurins evolved from bacterial tyrosine-aspartate (YD)-repeat protein precursors. Here, we discuss how structures of the C-terminal domain of teneurins, determined using X-ray crystallography and electron microscopy, support the earlier findings on the proteins’ ancestry. This chapter describes the structure of the teneurin scaffold with reference to a large family of teneurin-like proteins that are widespread in modern prokaryotes. The central scaffold of modern eukaryotic teneurins is decorated by additional domains typically found in bacteria, which are re-purposed in eukaryotes to generate highly multifunctional receptors. We discuss how alternative splicing contributed to further diversifying teneurin structure and thereby function. This chapter traces the evolution of teneurins from a structural point of view and presents the state-of-the-art of how teneurin function is encoded by its specific structural features

Shared values and deliberative valuation:Future directions

Valuation that focuses only on individual values evades the substantial collective and intersubjective meanings, significance and value from ecosystems. Shared, plural and cultural values of ecosystems constitute a diffuse and interdisciplinary field of research, covering an area that links questions around value ontology, elicitation and aggregation with questions of participation, ethics, and social justice. Synthesising understanding from various contributions to this Special Issue of Ecosystem Services, and with a particular focus on deliberation and deliberative valuation, we discuss key findings and present 35 future research questions in eight topic areas: 1) the ontology of shared values; 2) the role of catalyst and conflict points; 3) shared values and cultural ecosystem services; 4) transcendental values; 5) the process and outcomes of deliberation; 6) deliberative monetary valuation; 7) value aggregation, meta-values and ‘rules of the game’; and 8) integrating valuation methods. The results of this Special Issue and these key questions can help develop a more extensive evidence base to mature the area and develop environmental valuation into a more pluralistic, comprehensive, robust, legitimate and effective way of safeguarding ecosystems and their services for the future

Evaluating the performance of malaria genetics for inferring changes in transmission intensity using transmission modelling

Substantial progress has been made globally to control malaria, however there is a growing need for innovative new tools to ensure continued progress. One approach is to harness genetic sequencing and accompanying methodological approaches as have been used in the control of other infectious diseases. However, to utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment, which all impact the level of genetic diversity and relatedness of malaria parasites. We develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The model predicted malaria prevalence with a mean absolute error of 0.055. Different assumptions about the availability of sample metadata were considered, with the most accurate predictions of malaria prevalence made when the clinical status and age of sampled individuals is known. Parasite genetics may provide a novel surveillance tool for estimating the prevalence of malaria in areas in which prevalence surveys are not feasible. However, the findings presented here reinforce the need for patient metadata to be recorded and made available within all future attempts to use parasite genetics for surveillance

Presentation, Treatment, and Prognosis of Secondary Melanoma within the Orbit

BackgroundOcular melanoma is a rare but often deadly malignancy that arises in the uvea, conjunctiva, or orbit. Uveal melanoma is the most common type, with conjunctival melanoma being the second most frequently observed. Melanoma accounts for 5–10% of metastatic or secondary orbital malignancies, but only a minute proportion of primary orbital neoplasia. The aim of this study was to characterize the clinical presentation, treatment, and prognosis in patients presenting with melanoma metastatic to, or secondary within, the orbit.MethodsA retrospective cohort study of patients presenting to a tertiary referral orbital unit from 1982 to 2016 was performed. Eighty-nine patients with biopsy-proven diagnosis of melanoma within the orbit were included in the study. The clinical notes, radiological imaging, histology, surgical notes, and outcome data for the patients were reviewed. The main outcome measures of interest were the interval between primary malignant melanoma and orbital presentation, survival after orbital presentation, and clinical parameters (such as gender, age at presentation, and treatment approach).ResultsThe commonest primary source of tumor was choroidal melanoma, with conjunctival and cutaneous melanomas being relatively common; eyelid and naso-sinus tumors occurred in a few cases. The mean age at presentation with orbital disease was 65 years (31–97 years). The interval between primary malignancy and orbital disease (either local spread/recurrence or true metastatic disease) showed wide variability, with almost one-third of patients having orbital disease at the time of primary diagnosis, but others presenting many years later; indeed, the longest orbital disease-free interval was over 34 years. Twenty-three patients were considered to have had late orbital metastases—that is, at more than 36 months after primary tumor. The median survival following presentation with orbital involvement was 24 months. Patients with tumors of cutaneous origin had worst survival, whereas those with conjunctival tumors had the best prognosis.ConclusionA high index of suspicion for orbital recurrence should be maintained in any patient with prior history of melanoma, however distant the primary tumor is in site or time. Furthermore, giving a prognosis for orbital melanoma remains problematic due to highly variable survival, and further investigation will be necessary to understand the likely genetic basis of this phenomenon