Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.

Equipped to deal with uncertainty in climate and impacts predictions: lessons from internal peer review

The quantification of uncertainty is an increasingly popular topic, with clear importance for climate change policy. However, uncertainty assessments are open to a range of interpretations, each of which may lead to a different policy recommendation. In the EQUIP project researchers from the UK climate modelling, statistical modelling, and impacts communities worked together on ‘end-to-end’ uncertainty assessments of climate change and its impacts. Here, we use an experiment in peer review amongst project members to assess variation in the assessment of uncertainties between EQUIP researchers. We find overall agreement on key sources of uncertainty but a large variation in the assessment of the methods used for uncertainty assessment. Results show that communication aimed at specialists makes the methods used harder to assess. There is also evidence of individual bias, which is partially attributable to disciplinary backgrounds. However, varying views on the methods used to quantify uncertainty did not preclude consensus on the consequential results produced using those methods. Based on our analysis, we make recommendations for developing and presenting statements on climate and its impacts. These include the use of a common uncertainty reporting format in order to make assumptions clear; presentation of results in terms of processes and trade-offs rather than only numerical ranges; and reporting multiple assessments of uncertainty in order to elucidate a more complete picture of impacts and their uncertainties. This in turn implies research should be done by teams of people with a range of backgrounds and time for interaction and discussion, with fewer but more comprehensive outputs in which the range of opinions is recorded.

Researching farmer behaviour in climate change adaptation and sustainable agriculture: lessons learned from five case studies

Understanding farmer behaviour is needed for local agricultural systems to produce food sustainably while facing multiple pressures. We synthesize existing literature to identify three fundamental questions that correspond to three distinct areas of knowledge necessary to understand farmer behaviour: 1) decision-making model; 2) cross-scale and cross-level pressures; and 3) temporal dynamics. We use this framework to compare five interdisciplinary case studies of agricultural systems in distinct geographical contexts across the globe. We find that these three areas of knowledge are important to understanding farmer behaviour, and can be used to guide the interdisciplinary design and interpretation of studies in the future. Most importantly, we find that these three areas need to be addressed simultaneously in order to understand farmer behaviour. We also identify three methodological challenges hindering this understanding: the suitability of theoretical frameworks, the trade-offs among methods and the limited timeframe of typical research projects. We propose that a triangulation research strategy that makes use of mixed methods, or collaborations between researchers across mixed disciplines, can be used to successfully address all three areas simultaneously and show how this has been achieved in the case studies. The framework facilitates interdisciplinary research on farmer behaviour by opening up spaces of structured dialogue on assumptions, research questions and methods employed in investigation.

South Africa and constructive engagement: lessons learned?

There has been much criticism of President Mbeki's policy of constructive engagement towards Mugabe's regime in Zimbabwe. This has grown since 2000 as the crisis has continued to worsen. This article compares Pretoria's current approach with the Reagan administration's constructive engagement towards Pretoria in the 1980s. Washington made a number of significant mistakes in the design and implementation of this policy and each of these is examined. An investigation of Mbeki's actions concludes that he is currently committing many of the same errors. Not only does this damage Mbeki's credibility, it also damages the credibility of a vital diplomatic tool - reducing constructive engagement once again to a diplomatic fig leaf to cover 'business as usual' with a rogue state.

The new localism, anti-political development machines, and the role of planning consultants: lessons from London's South Bank

This paper draws on a study of the politics of development planning in London’s South Bank to examine wider trends in the governance of contemporary cities. It assesses the impacts and outcomes of so-called new localist reforms and argues that we are witnessing two principal trends. First, governance processes are increasingly dominated by anti-democratic development machines, characterized by new assemblages of public- and private-sector experts. These machines reflect and reproduce a type of development politics in which there is a greater emphasis on a pragmatic realism and a politics of delivery. Second, the presence of these machines is having a significant impact on the politics of planning. Democratic engagement is not seen as the basis for new forms of localism and community control. Instead, it is presented as a potentially disruptive force that needs to be managed by a new breed of skilled private-sector consultant. The paper examines these wider shifts in urban politics before focusing on the connections between emerging development machines and local residential and business communities. It ends by highlighting some of the wider implications of change for democratic modes of engagement and nodes of resistance in urban politics.

Briefing paper for universities on Core Maths

This briefing paper outlines the rationale for and development of the new Core Maths qualifications, the characteristics of Core Maths, and why Core Maths is important for higher education. It is part of a communication to university vice-chancellors from the Department for Business, Innovation and Skills (BIS) comprising this paper and a joint Ministerial letter from Jo Johnson, Minister of State for Universities and Science in BIS, and Nick Gibb, Minister of State for Schools in the Department for Education (DfE).

Good practice for pupils learning English as an additional language; lessons from effective literacy teachers in inner city primary schools.

This article presents observations and discussion of the successful teaching of English to pupils, in English primary schools, for whom English is an additional language (EAL). It draws on research in Year 2 (6/7year old) classes in three inner-city primary schools carried out in 2003 and 2005. Three recognised, effective teachers of literacy were selected for case study; all worked in successful schools where results for literacy, measured by national tests, were in line with or better than national averages. Following analyses of lesson observations and interviews with the teachers, their Headteachers and the EAL co-ordinators in the schools, a number of common elements in their practice emerged. Discussion centres on how these pedagogical features supported effective learning environments for the early literacy development of bilingual children, and on the implications for the practice of teaching English to all pupils.

Promoting core maths - background, evidence, plans, opportunities, and challenges

This article discusses some of the issues relating to the promotion of Core Maths to students, parents, schools and colleges and their senior leadership teams, and also to employers and higher education (HE). Some challenges are highlighted, and addressed, with suggestions for ways forward to secure the future of Core Maths and widespread adoption by all stakeholders. A summary of the background reports that led to the introduction of Core Maths, and the related educational landscape prior to its introduction, is included.

Diversity lessons from Wales: how marketing bilingualism contributes to language shift and language maintenance

Wales is one of the constituent nations of the United Kingdom. While sharing much of its political and social history with England, Scotland, and Northern Ireland, it has retained a distinct cultural identity.In particular, over 560,000 people, a significant minority of the population of 2.2 million, speak Welsh, a member of the Celtic family of languages, and the country is officially bilingual. In this paper, we will look at attempts to maintain and grow the number of speakers of the language and at the relevance of this development for speakers of minority languages in other settings.