Detecting ecological thresholds and tipping points in the natural capital assets of a protected coastal ecosystem.

Concern about abrupt and potentially irreversible ecosystem thresholds and tipping points is increasing, as they may have significant implications for natural capital and human wellbeing. Although well established in theory, there are few empirical studies that provide evidence for these phenomena in coastal and estuarine ecosystems, despite their high value for provision of ecosystem services. To determine the likelihood of such events, we tested two statistical methods; sequential T-test analysis (STARS) and generalised additive models (GAMs) in a harbour ecosystem. These methods were applied to time series data spanning up to 25 years coupled with analysis of the relationships between drivers and natural capital asset flows. Results of the STARS analysis identified nonlinear thresholds in three of the natural capital assets of Poole harbour; mudflat area, Manila clam stocks and wader/wildfowl numbers, as well as an increase in several drivers affecting the harbour. The most prominent threshold was recorded in the Manila clam fisheries of the harbour, with stocks in two locations of the harbour declining by 73–78% between 2006 and 2008. We suggest that the historic decline in the Manila clam stocks of the harbour were partly attributable to illegal fishing pressure although other factors such as disease and lease bed holders switching to other species were also likely to have contributed. More recently (2015-onwards) wild clam stocks of the harbour have increased thanks to improved management measures by local authorities. Generalised additive models also identified the contribution of macroalgal mats, sediment shoaling and river flows to historic changes in mudflat area, saltmarsh area and wader/wildfowl numbers. We conclude that information on thresholds and tipping points obtained using these approaches can potentially be of value in a management context, by focusing attention on the interactions and positive feedbacks between drivers that may cause abrupt change in coastal ecosystems

Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors

Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) < 0.05 %. Functional annotation using six computational algorithms, experimental evidence and structural data identified 156/740 (21 %) SNVs as potentially damaging to GPCR function, most commonly in regions encoding the transmembrane and C-terminal intracellular receptor domains. In 31 index cases with IPFDs (Gi-pathway defect n=15; secretion defect n=11; thromboxane pathway defect n=3 and complex defect n=2) there were 256 SNVs in the target regions of 15 stimulatory platelet GPCRs (34 unique; 12 with MAF< 1 % and 22 with MAF≥ 1 %). These included rare variants predicting R122H, P258T and V207A substitutions in the P2Y12 receptor that were annotated as potentially damaging, but only partially explained the platelet function defects in each case. Our data highlight that potentially damaging variants in platelet GPCR genes have low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes

DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6

Background: There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti-angiogenic and cytotoxic chemotherapy in colorectal cancer (CRC) liver metastases. Methods: Ten patients with 26 CRC liver metastases had two dynamic contrast-enhanced MRI (DCE-MRI) examinations before starting first-line bevacizumab and FOLFOX-6. Pre-treatment biomarkers of tumour microvasculature were computed and a regression analysis was performed against the post-treatment change in tumour volume after five cycles of therapy. The ability of the resulting linear model to predict tumour shrinkage was evaluated using leave-one-out validation. Robustness to inter-visit variation was investigated using data from a second baseline scan. Results: In all, 86% of the variance in post-treatment tumour shrinkage was explained by the median extravascular extracellular volume (ve), tumour enhancing fraction (EF), and microvascular uniformity (assessed with the fractal measure box dimension, d0) (R2=0.86, P<0.00005). Other variables, including baseline volume were not statistically significant. Median prediction error was 12%. Equivalent results were obtained from the second scan. Conclusion: Traditional image analyses may over-simplify tumour biology. Measuring microvascular heterogeneity may yield important prognostic and/or predictive biomarkers

Solution of a one-dimensional stochastic model with branching and coagulation reactions

We solve an one-dimensional stochastic model of interacting particles on a chain. Particles can have branching and coagulation reactions, they can also appear on an empty site and disappear spontaneously. This model which can be viewed as an epidemic model and/or as a generalization of the {\it voter} model, is treated analytically beyond the {\it conventional} solvable situations. With help of a suitably chosen {\it string function}, which is simply related to the density and the non-instantaneous two-point correlation functions of the particles, exact expressions of the density and of the non-instantaneous two-point correlation functions, as well as the relaxation spectrum are obtained on a finite and periodic lattice.Comment: 5 pages, no figure. To appear as a Rapid Communication in Physical Review E (September 2001

Generalized empty-interval method applied to a class of one-dimensional stochastic models

In this work we study, on a finite and periodic lattice, a class of one-dimensional (bimolecular and single-species) reaction-diffusion models which cannot be mapped onto free-fermion models. We extend the conventional empty-interval method, also called {\it interparticle distribution function} (IPDF) method, by introducing a string function, which is simply related to relevant physical quantities. As an illustration, we specifically consider a model which cannot be solved directly by the conventional IPDF method and which can be viewed as a generalization of the {\it voter} model and/or as an {\it epidemic} model. We also consider the {\it reversible} diffusion-coagulation model with input of particles and determine other reaction-diffusion models which can be mapped onto the latter via suitable {\it similarity transformations}. Finally we study the problem of the propagation of a wave-front from an inhomogeneous initial configuration and note that the mean-field scenario predicted by Fisher's equation is not valid for the one-dimensional (microscopic) models under consideration.Comment: 19 pages, no figure. To appear in Physical Review E (November 2001

Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus

Background: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. Methods: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. Results: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06 ± 0.07, p = 0.44; Bland-Altman 95% limits of agreement -2.19–2.08 mm3, bias of -0.06 mm3) and per vessel (3.1 mm3 ± -2.85 mm3, p = 0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3 ± 0.09mm3, p < 0.001; 95% LoA -6.78 to 2.25 mm3, bias of -2.2 mm3) and per vessel (33.04 ± 10.3 mm3, p < 0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. Conclusion: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.Ravi Kiran Munnur, Jordan Andrews ... Dorothy Keefe ... Lorelle Smith ... Joanne Bowen ... Sarah Thompson ... et al

Interventions Targeting Child Undernutrition in Developing Countries May Be Undermined by Dietary Exposure to Aflatoxin

Child undernutrition, a form of malnutrition, is a major public health burden in developing countries. Supplementation interventions targeting the major micronutrient deficiencies have only reduced the burden of child undernutrition to a certain extent, indicating that there are other underlying determinants that need to be addressed. Aflatoxin exposure, which is also highly prevalent in developing countries, may be considered an aggravating factor for child undernutrition. Increasing evidence suggests that aflatoxin exposure can occur in any stage of life, including in utero through a trans-placental pathway and in early childhood (through contaminated weaning food and family food). Early life exposure to aflatoxin is associated with adverse effects on low birth weight, stunting, immune suppression, and the liver function damage. The mechanisms underlying impaired growth and aflatoxin exposure are still unclear but intestinal function damage, reduced immune function, and alteration in the insulin-like growth factor axis caused by the liver damage are the suggested hypotheses. Given the fact that both aflatoxin and child undernutrition are common in sub-Saharan Africa, effective interventions aimed at reducing undernutrition cannot be satisfactorily achieved until the interactive relationship between aflatoxin and child undernutrition is clearly understood, and an aflatoxin mitigation strategy takes effect in those vulnerable mothers and children

Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at $\lg(E/{\rm eV})=18.5-19.0$ differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass $A > 4$. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Academic language socialisation in high school writing conferences

This study examines multilingual high school writers’ individual talk with their teachers in two advanced English language development classes to observe how such talk shapes linguistically diverse adolescents’ writing. Addressing adolescent writers’ language socialization through microethnographic discourse analysis, the author argues that teachers’ oral responses during writing conferences can either scaffold or deter students’ socialization into valued ways of using academic language for school writing. She suggests what forms of oral response provide scaffolding and what forms might limit multilingual adolescent learners’ academic literacy. Constructive interactions engaged students in dialogue about their writing, and students included content or phrasing from the interaction in their texts. Unhelpful interactions failed to foster students’ language development in observable ways. Although teachers attempted to scaffold ideas and language, they often did not guide students’ discovery of appropriate forms or points. These interactions represent restrictive academic language socialization: while some students did create academic texts, they learned little about academic language use