Oxford Brookes University

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

A number of issues can affect sample size in qualitative research; however, the guiding principle should be the concept of saturation. This has been explored in detail by a number of authors but is still hotly debated, and some say little understood. A sample of PhD studies using qualitative approaches, and qualitative interviews as the method of data collection was taken from theses.com and contents analysed for their sample sizes. Five hundred and sixty studies were identified that fitted the inclusion criteria. Results showed that the mean sample size was 31; however, the distribution was non-random, with a statistically significant proportion of studies, presenting sample sizes that were multiples of ten. These results are discussed in relation to saturation. They suggest a pre-meditated approach that is not wholly congruent with the principles of qualitative research. URN: urn:nbn:de:0114-fqs100387

Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft-mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.

Our aim was to differentiate the screening potential of waist-to-height ratio (WHtR) and waist circumference (WC) for adult cardiometabolic risk in people of different nationalities and to compare both with body mass index (BMI). We undertook a systematic review and meta-analysis of studies that used receiver operating characteristics (ROC) curves for assessing the discriminatory power of anthropometric indices in distinguishing adults with hypertension, type-2 diabetes, dyslipidaemia, metabolic syndrome and general cardiovascular outcomes (CVD). Thirty one papers met the inclusion criteria. Using data on all outcomes, averaged within study group, WHtR had significantly greater discriminatory power compared with BMI. Compared with BMI, WC improved discrimination of adverse outcomes by 3% (P < 0.05) and WHtR improved discrimination by 4-5% over BMI (P < 0.01). Most importantly, statistical analysis of the within-study difference in AUC showed WHtR to be significantly better than WC for diabetes, hypertension, CVD and all outcomes (P < 0.005) in men and women. For the first time, robust statistical evidence from studies involving more than 300 000 adults in several ethnic groups, shows the superiority of WHtR over WC and BMI for detecting cardiometabolic risk factors in both sexes. Waist-to-height ratio should therefore be considered as a screening tool.

<b>Background</b> While the patient and public involvement (PPI) evidence base has expanded over the past decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it works, in what context, for whom, and why. <b>Objective</b> To develop international consensus on the key items to report to enhance the quality, transparency, and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP2. <b>Methods</b> The EQUATOR method for developing reporting guidelines was used. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process. <b>Results</b> 143 participants agreed to participate in round one, with an 86% (123/143) response for round two and a 78% (112/143) response for round three. The Delphi survey identified the need for long form (LF) and short form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment, and reflections and is suitable for studies where the main focus is PPI. GRIPP2-SF includes five items on aims, methods, results, outcomes, and critical perspective and is suitable for studies where PPI is a secondary focus. <b>Conclusions</b> GRIPP2-LF and GRIPP2-SF represent the first international evidence based, consensus informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency, and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. In order to encourage its wide dissemination this article is freely accessible on <i>The BMJ</i> and <i>Research Involvement and Engagement</i> journal websites.

Adaptive tracking-by-detection methods are widely used in computer vision for tracking arbitrary objects. Current approaches treat the tracking problem as a classification task and use online learning techniques to update the object model. However, for these updates to happen one needs to convert the estimated object position into a set of labelled training examples, and it is not clear how best to perform this intermediate step. Furthermore, the objective for the classifier (label prediction) is not explicitly coupled to the objective for the tracker (accurate estimation of object position). In this paper, we present a framework for adaptive visual object tracking based on structured output prediction. By explicitly allowing the output space to express the needs of the tracker, we are able to avoid the need for an intermediate classification step. Our method uses a kernelized structured output support vector machine (SVM), which is learned online to provide adaptive tracking. To allow for real-time application, we introduce a budgeting mechanism which prevents the unbounded growth in the number of support vectors which would otherwise occur during tracking. Experimentally, we show that our algorithm is able to outperform state-of-the-art trackers on various benchmark videos. Additionally, we show that we can easily incorporate additional features and kernels into our framework, which results in increased performance.

Abstract Sustainable development is a widely used term, which has been increasingly influential on UK planning, housing and urban policy in recent years. Debates about sustainability no longer consider sustainability solely as an environmental concern, but also incorporate economic and social dimensions. However, while a social dimension to sustainability is widely accepted, exactly what this means has not been very clearly defined or agreed. This paper aims to address this disparity through a detailed exploration and definition of the concept of social sustainability within the urban context. The relationship between urban form and social sustainability is explored and two main dimensions of social sustainability are identified and discussed in detail: equitable access and the sustainability of the community itself. Copyright © 2009 John Wiley &amp; Sons, Ltd and ERP Environment.

While the patient and public involvement (PPI) evidence base has expanded over the past decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it works, in what context, for whom, and why. To develop international consensus on the key items to report to enhance the quality, transparency, and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP2. The EQUATOR method for developing reporting guidelines was used. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process. One hundred forty-three participants agreed to participate in round one, with an 86% (123/143) response for round two and a 78% (112/143) response for round three. The Delphi survey identified the need for long form (LF) and short form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment, and reflections and is suitable for studies where the main focus is PPI. GRIPP2-SF includes five items on aims, methods, results, outcomes, and critical perspective and is suitable for studies where PPI is a secondary focus. GRIPP2-LF and GRIPP2-SF represent the first international evidence based, consensus informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency, and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. In order to encourage its wide dissemination this article is freely accessible on The BMJ and Research Involvement and Engagement journal websites.

In this paper, we review the different definitions of resilience and their potential application in explaining the long-term development of urban and regional economies. We reject equilibrist versions of resilience and argue instead that we should seek an understanding of the concept from an evolutionary perspective. After discussing a number of such perspectives, we focus on the adaptive cycle model from panarchy theory to generate testable hypotheses concerning urban and regional resilience. Two case study city-regional economies are used to explore this model. We conclude that the evolutionary adaptive cycle model, though not without problems, warrants further study as a framework for analysing regional economic resilience.

Nonhuman primates, our closest biological relatives, play important roles in the livelihoods, cultures, and religions of many societies and offer unique insights into human evolution, biology, behavior, and the threat of emerging diseases. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. Current information shows the existence of 504 species in 79 genera distributed in the Neotropics, mainland Africa, Madagascar, and Asia. Alarmingly, ~60% of primate species are now threatened with extinction and ~75% have declining populations. This situation is the result of escalating anthropogenic pressures on primates and their habitats-mainly global and local market demands, leading to extensive habitat loss through the expansion of industrial agriculture, large-scale cattle ranching, logging, oil and gas drilling, mining, dam building, and the construction of new road networks in primate range regions. Other important drivers are increased bushmeat hunting and the illegal trade of primates as pets and primate body parts, along with emerging threats, such as climate change and anthroponotic diseases. Often, these pressures act in synergy, exacerbating primate population declines. Given that primate range regions overlap extensively with a large, and rapidly growing, human population characterized by high levels of poverty, global attention is needed immediately to reverse the looming risk of primate extinctions and to attend to local human needs in sustainable ways. Raising global scientific and public awareness of the plight of the world's primates and the costs of their loss to ecosystem health and human society is imperative.

This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.

A number of research studies have investigated tourist satisfaction with mass tourism destinations, particularly during the peak (summer) season. However, there has been limited investigation of tourist satisfaction with off-season holiday destinations. This article reports the findings of a study to determine destination attributes critical to the over-all satisfaction levels of tourists visiting Mallorca, Spain, during the winter season. Their future holiday intentions also are investigated. Findings are analyzed, and implications and limitations are discussed.

BACKGROUND AND AIMS: Silicon (Si) in plants provides structural support and improves tolerance to diseases, drought and metal toxicity. Shoot Si concentrations are generally considered to be greater in monocotyledonous than in non-monocot plant species. The phylogenetic variation in the shoot Si concentration of plants reported in the primary literature has been quantified. METHODS: Studies were identified which reported Si concentrations in leaf or non-woody shoot tissues from at least two plant species growing in the same environment. Each study contained at least one species in common with another study. KEY RESULTS: Meta-analysis of the data revealed that, in general, ferns, gymnosperms and angiosperms accumulated less Si in their shoots than non-vascular plant species and horsetails. Within angiosperms and ferns, differences in shoot Si concentration between species grouped by their higher-level phylogenetic position were identified. Within the angiosperms, species from the commelinoid monocot orders Poales and Arecales accumulated substantially more Si in their shoots than species from other monocot clades. CONCLUSIONS: A high shoot Si concentration is not a general feature of monocot species. Information on the phylogenetic variation in shoot Si concentration may provide useful palaeoecological and archaeological information, and inform studies of the biogeochemical cycling of Si and those of the molecular genetics of Si uptake and transport in plants.

The role of organisational innovativeness, or innovative capability, in attaining competitive advantage has been widely discussed. Most research examines innovation activities and their associations with organisational characteristics, or investigates certain perspectives of innovative capability, such as product innovation. Much less attention, however, has been paid to develop and validate measurement constructs of organisational innovativeness. Through an extensive literature review, five dimensions of an organisation's overall innovativeness are identified. These five dimensions form the component factors of the organisational innovativeness construct. Following a three‐step approach, a final 20‐item measurement construct is validated. Theoretical and methodological issues in relation to application of the organisational innovativeness construct are discussed in light of these findings.

Renewed interest in fission-fusion dynamics is due to the recognition that such dynamics may create unique challenges for social interaction and distinctive selective pressures acting on underlying communicative and cognitive abilities. New frameworks for integrating current knowledge on fission-fusion dynamics emerge from a fundamental rethinking of the term "fission-fusion" away from its current general use as a label for a particular modal type of social system (i.e., "fission-fusion societies"). Specifically, because the degree of spatial and temporal cohesion of group members varies both within and across taxa, any social system can be described in terms of the extent to which it expresses fission-fusion dynamics. This perspective has implications for socioecology, communication, cognitive demands, and human social evolution.

We suggest that a simple, rapid screening tool-the waist-to-height ratio (WHTR)-could help to overcome debates about the use of different body mass index (BMI) boundary values for assessing health risks in different populations. There are six reasons for our proposal: WHTR is more sensitive than BMI as an early warning of health risks. WHTR is cheaper and easier to measure and calculate than BMI. A boundary value of WHTR = 0.5 indicates increased risk for men and women. A boundary value of WHTR = 0.5 indicates increased risk for people in different ethnic groups. WHTR boundary values can be converted into a consumer-friendly chart. WHTR may allow the same boundary values for children and adults. Communicating messages about health risk could be much simpler if the same anthropometric index and the same public health message can be used throughout childhood, into adult life, and throughout the world. This simple message is: Keep your waist circumference to less than half your height.

OBJECTIVE: To facilitate the Food and Agriculture Organization/World Health Organization/United Nations University Joint (FAO/WHO/UNU) Expert Consultation on Energy and Protein Requirements which met in Rome in 1981, Schofield et al. reviewed the literature and produced predictive equations for both sexes for the following ages: 0-3, 3-10, 10-18, 18-30, 30-60 and >60 years. These formed the basis for the equations used in 1985 FAO/WHO/UNU document, Energy and Protein Requirements. While Schofield's analysis has served a significant role in re-establishing the importance of using basal metabolic rate (BMR) to predict human energy requirements, recent workers have subsequently queried the universal validity and application of these equations. A survey of the most recent studies (1980-2000) in BMR suggests that in most cases the current FAO/WHO/UNU predictive equations overestimate BMR in many communities. The FAO/WHO/UNU equations to predict BMR were developed using a database that contained a disproportionate number--3388 out of 7173 (47%)--of Italian subjects. The Schofield database contained relatively few subjects from the tropical region. The objective here is to review the historical development in the measurement and application of BMR and to critically review the Schofield et al. BMR database presenting a series of new equations to predict BMR. DESIGN: This division, while arbitrary, will enable readers who wish to omit the historical review of BMR to concentrate on the evolution of the new BMR equations. SETTING: BMR data collected from published and measured values. SUBJECTS: A series of new equations (Oxford equations) have been developed using a data set of 10,552 BMR values that (1) excluded all the Italian subjects and (2) included a much larger number (4018) of people from the tropics. RESULTS: In general, the Oxford equations tend to produce lower BMR values than the current FAO/WHO/UNU equations in 18-30 and 30-60 year old males and in all females over 18 years of age. CONCLUSIONS: This is an opportune moment to re-examine the role and place of BMR measurements in estimating total energy requirements today. The Oxford equations' future use and application will surely depend on their ability to predict more accurately the BMR in contemporary populations.

The metabolic network of the catabolic, energy and biosynthetic metabolism of Escherichia coli is a paradigmatic case for the large genetic and metabolic networks that functional genomics efforts are beginning to elucidate. To analyse the structure of previously unknown networks involving hundreds or thousands of components by simple visual inspection is impossible, and quantitative approaches are needed to analyse them. We have undertaken a graph theoretical analysis of the E. coli metabolic network and find that this network is a small-world graph, a type of graph distinct from both regular and random networks and observed in a variety of seemingly unrelated areas, such as friendship networks in sociology, the structure of electrical power grids, and the nervous system of Caenorhabditis elegans. Moreover, the connectivity of the metabolites follows a power law, another unusual but by no means rare statistical distribution. This provides an objective criterion for the centrality of the tricarboxylic acid cycle to metabolism. The small-world architecture may serve to minimize transition times between metabolic states, and contains evidence about the evolutionary history of metabolism.

BACKGROUND AND AIMS: Reducing mortality from colorectal cancer (CRC) may be achieved by the introduction of population-based screening programs. The aim of the systematic review was to update previous research to determine whether screening for CRC using the fecal occult blood test (FOBT) reduces CRC mortality and to consider the benefits, harms, and potential consequences of screening. METHODS: We searched eight electronic databases (Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, SIGLE, and HMIC). We identified nine articles describing four randomized controlled trials (RCTs) involving over 320,000 participants with follow-up ranging from 8 to 18 yr. The primary analyses used intention to screen and a secondary analysis adjusted for nonattendance. We calculated the relative risks and risk differences for each trial, and then overall, using fixed and random effects models. RESULTS: Combined results from the four eligible RCTs indicated that screening had a 16% reduction in the relative risk (RR) of CRC mortality (RR 0.84, 95% confidence interval [CI] 0.78-0.90). There was a 15% RR reduction (RR 0.85, 95% CI 0.78-0.92) in CRC mortality for studies that used biennial screening. When adjusted for screening attendance in the individual studies, there was a 25% RR reduction (RR 0.75, 95% CI 0.66-0.84) for those attending at least one round of screening using the FOBT. There was no difference in all-cause mortality (RR 1.00, 95% CI 0.99-1.02) or all-cause mortality excluding CRC (RR 1.01, 95% CI 1.00-1.03). CONCLUSIONS: The present review includes seven new publications and unpublished data concerning CRC screening using FOBT. This review confirms previous research demonstrating that FOBT screening reduces the risk of CRC mortality. The results also indicate that there is no difference in all-cause mortality between the screened and nonscreened populations.

A clearly structured overview of a key subject, this work provides the student with not only a complete introductory text but also a book to support further studies. Written by three authors with extensive research and practical experience in Environmental Impact Assessment (EIA), the treatment is up to date and brings together currently fragmented information from many sources.&nbsp; EIA is now firmly on the agenda as a result of the introduction of legislation at both national and international levels, and is very much in tune with widespread and growing concern about environmental issues and the impact of development on the environment. First introduced in the USA in the 1970s, the application of EIA has been accelerated in Europe by the 1985 EC directive, which led to its introduction in the UK in 1988, since when it has been a major growth area in planning practice. The originally anticipated 20 environmental impact statements per annum have now grown to well over 300, for projects such as power stations, roads, new settlements, mineral extraction schemes, waste-disposal installations and toursism developments, and this is but the tip of the iceberg. Based on highly successful courses at one of the leading schools of planning, this book should serve the need for an introduction to EIA that goes beyond first principles and is informed by a wealth of teaching, research and practical experience. Students on undergraduate and postgraduate planning programmes should find it useful as a course text, as will students of environmental management/policy, environmental sciences/studies, geography and the built environment. Planners, developers and decision makers in government and business should also welcome the book as a very effective means of getting to grips with a key new subject which they must fully integrate with their other activities.