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Supplemental Figure 1. In vitro cytotoxicity assay

Purpose: Chimeric antigen receptor–modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs).Experimental Design: We conducted a phase I trial to test HAI of CAR-T in patients with CEA+ liver metastases. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (108, 109, and 1010 cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (1010 cells × 3) along with systemic IL2 support.Results: Four patients had more than 10 liver metastases, and patients received a mean of 2.5 lines of conventional systemic therapy before enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI, and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range, 19%–48%) from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases.Conclusions: We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted. Clin Cancer Res; 21(14); 3149–59. ©2015 AACR.

Supplemental Figure 4. Cytokine response to treatment

Supplemental Figure 3. Radiographic studies

Supplemental Figure 2. Flow cytometry gating

The tryptophan (trp) operon in E. coli codes for the proteins responsible for the synthesis of the amino acid tryptophan from chorismic acid, and has been one of the most well-studied gene networks since its discovery in the 1960s. The tryptophanase (tna) operon codes for proteins needed to transport and metabolize it. Both of these have been modeled individually with delay differential equations under the assumption of mass-action kinetics. Recent work has provided strong evidence for bistable behavior of the tna operon. The authors of (Orozco, 2019) identified a medium range of tryptophan in which the system has two stable steady-states, and they reproduced these experimentally. In this paper, we will show how a Boolean model can capture this bistability. We will also develop and analyze a Boolean model of the trp operon. Finally, we will combine these two to create a single Boolean model of the transport, synthesis, and metabolism of tryptophan. In this amalgamated model, the bistability disappears, presumably reflecting the ability of the trp operon to produce tryptophan and drive the system toward homeostasis. All of these models have longer attractors that we call "artifacts of synchrony", which disappear in the asynchronous automata. This curiously matches the behavior of a recent Boolean model of the arabinose operon in E. coli, and we discuss some open-ended questions that arise along these lines., Comment: 33 pages, 12 figures

One of the latest trends in the global aviation industry is to use "smart" technologies and interfaces as time saving and efficiency tools. Larger flight instrument displays have replaced conventional, analogue, instruments and can be combined with touch screen efficiency tools. Their ever-increasing size brings with them issues relating to light emissions and eye absorption. Especially emissions of certain colours of light at certain times affecting the Pilots circadian rhythms and cause eye fatigue - which is recognised to have an impact on Pilots performance. (Davies R., 2018) This research paper complements the current study and measurement of stress, fatigue and human factors with respect to increasing artificial light intensity experienced by Pilots on the Flight Deck. The authors present the results of several measurements taken using a flight simulator which meets the current regulations for Pilot training. However, the conditions have been adjusted to the realistic conditions of a Flight Deck. The research results provide Air Operators, Airlines and aeronautical designers with valuable data on human behaviour and the reactions to Flight Deck environmental changes. For the purpose of our research, we decided to use eye monitoring technology to record eye movements to determine the pilot’s performance. Eye monitoring provides data on the number of eye movements, fixations and the durations of these.

Research background:The authors are providing an update to the ongoing process of Brexit and the negotiations between the UK and the EU, following their own previous research in this area.Purpose of the article:In 2019, the aviation sector in the UK ranked as the third largest in the world. London Heathrow, a hub to many UK airlines, ranked as Europe’s busiest airport and seventh busiest in the world. [1] Brexit negotiations between the UK and the EU, in the context of globalization and the existing deep ties within the EU institutions, presents a complex task. Following the Brexit referendum in June 2016, where the majority of the electorate decided that Britain should leave the EU, events have progressed significantly by the UK leaving the EU formally at 23:59 on the 31st January 2020. However, negotiations are still ongoing and when it comes to Aviation, the outcome in many key areas is still uncertain.Methods:The article is based on data and information collation as well as the authors’ experience within the industry.Findings & Value added:Once the transition period terminates on the 31st December 2020, Brexit will have a significant influence on trading in the European domestic market and globally on the international market. This paper discusses available options for the UK and the EU that follow from existing decisions in the Brexit bill, as well as outlining possible future developments. Furthermore, in light of the existing threats to the Aviation industry from the ongoing COVID-19 pandemic and the cessation of air travel for many weeks, adjustments to the Brexit plan might be required.

Protein tertiary structure determines protein function and is itself determined by the DNA sequence of the gene encoding the protein. However, the relationship between a gene’s DNA sequence and the corresponding protein’s tertiary structure is imperfectly understood. Spectral clustering has been used to address our understanding of this relationship. Spectral clustering is a graph partitioning algorithm derived from the Laplacian matrix of a network, which mathematically is often called a graph. The spectral clustering technique partitions a given data set into smaller different clusters based on some specific properties. Data sets within a cluster have more similarities than the data sets between clusters. Recently this method gained popularity for its simple implementation and efficient performance. In this chapter, we use spectral clustering methods to investigate and compare protein tertiary structures. This chapter provides insights into evolutionary relationships of protein functions.

Gene expression must be carefully regulated in order for a cell to maintain homeostasis. In prokaryotes, genes are often clustered together and co-transcribed, meaning that small groups of genes governing a specific cellular function will be either all “ON” or all “OFF.” Such a cluster of genes is called an operon, and these come in four basic types. Operons can be inducible or repressible, depending on whether they are ON or OFF by default. Additionally, the method of regulation can be positive or negative, depending on whether a repressor protein prevents transcription or an activator protein stimulates it. Classically, mathematical biologists have modeled operons using differential equations derived from the laws of mass-action kinetics. More recently, they have been modeled using discrete approaches such as Boolean and logical networks. In this chapter, we introduce the concept of a local model over a finite set, which is basically a collection of functions without specifying anything about dynamics or how they are composed. This unifies both Boolean and logical networks into a single framework. Given a local model, the functions can be updated synchronously, defining a finite dynamical system (FDS), or asynchronously, as is often done with logical models. Naturally, there are other update schemes as well, but we will just consider these two basic ones in this chapter. After comparing the so-called synchronous and asynchronous “state spaces” of local models, we will prove bijections between local models, synchronous state spaces, and asynchronous state spaces. Also in this chapter, we will introduce two basic operons in the model organism Escherichia coli: the lactose (lac) and arabinose (ara) operons. We will show how to model these gene regulatory networks as local models, and how to use computational algebra and freely available software tools for their analysis. Specifically, we will use the Macaulay2 computational algebra software, the Gene Interaction Network simulation (GINsim), and a new online crowd-sourced platform called TURING: Algorithms for Computation with Finite Dynamical Systems.

BACKGROUND Chimeric antigen receptor (CAR)-modified “designer” T cells (dTc, CAR-T) against PSMA selectively target antigen-expressing cells in vitro and eliminate tumors in vivo. Interleukin 2 (IL2), widely used in adoptive therapies, was proven essential in animal models for dTc to eradicate established solid tumors. METHODS Patients under­went chemotherapy condi­tion­ing, followed by dTc dosing under a Phase I escalation with continuous infusion low dose IL2 (LDI). A target of dTc escalation was to achieve ≥20% engraftment of infused activated T cells. RESULTS Six patients enrolled with doses prepared of whom five were treated. Patients received 109 or 1010 autologous T cells, achieving expansions of 20–560-fold over 2 weeks and engraftments of 5–56%. Pharmacokinetic and pharmacodynamic analyses established the impact of conditioning to promote expansion and engraftment of the infused T cells. Unexpectedly, administered IL2 was depleted up to 20-fold with high engraftments of activated T cells (aTc) in an inverse correlation (P

This article provides evidence on what developing country governments expect to be their main challenges within five to 10 years, and how they want their relationships with development assistance providers to evolve in order to meet these challenges. The results, based on a survey commissioned by the Organisation for Economic Co-operation and Development (OECD) of 40 partner country governments, indicate that demand for official development assistance (ODA) is likely to remain strong in the medium term, but that partner countries are actively diversifying providers in order to spread risk. Countries want ODA providers to shift to a more enabling role in the coming years, providing vital finance, but in support of government-led sector programmes, delivering more and better technical and policy support, and leveraging more private finance.

The nature of development co-operation has changed rapidly in recent years. Developing countries have access to a more diverse range of financing sources, including non-traditional providers of bilateral development co-operation, new or emerging multilateral and regional institutions, philanthropic organizations and private investors. These changes raise pressing questions about how the policies and practices of external providers of development finance must evolve, both to meet changing development priorities and to ensure that the overall development assistance effort from all providers is optimal. This article introduces a special issue of Development Policy Review that presents new perspectives from developing countries on the roles that development finance should play. This introduction highlights commonalities and differences among the articles contained in the special issue, and concludes with next steps for research and policy.

Ushered into the international development arena around the turn of this century by the German economist Inge Kaul, the concept of a global public good was an abstruse and surprising hit. Variations on it have found their way into most donor countries’ aid policy narratives. Kaul herself has long argued that international development assistance should not be used for the production of global public goods. Nevertheless, donor agencies have thoroughly appropriated the concept. In this paper, I do two things. First, I argue that the concept of a global public good has generally been used in an unduly restricted and self-serving way in aid policy narratives, as a euphemism for ‘solutions to transboundary problems of particular concern to donor countries’. I further argue that it might be deployed to greater effect were it linked more specifically to concrete, realistic global public policy commitments aimed at eliminating certain of the world’s ‘bads’—by, in effect, declaring them public enemies. I stress that global public policy commitments need not always yield net benefits for all. Some, morally based, might benefit only defined groups, as in the case of a global refugee resettlement regime. All such commitments, however, have in common a ‘whatever it takes’ character and credible means of implementation. Second, I here release, in an annex, the full transcript of an extended interview about the financing of global public goods that I conducted with Kaul in May 2015. This complements the material in the body of the paper because, while my own views about aid and global public goods do not completely accord with Kaul’s, particularly in relation to the use of aid to support the production of such goods, they were formed in part through reflection over a period of time on our 2015 discussion.

Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor-modified T-cell (CAR-T) hepatic artery infusions (HAI) for unresectable carcinoembryonic antigen (CEA)+ liver metastases (LM). High neutrophil:lymphocyte ratios (NLR) predict poor outcome in cancer patients and we hypothesized that NLR changes would correlate with early responses to CAR-T HAI. Six patients completed the protocol. Three patients received CAR-T HAI in dose escalation (1 × 10(8), 1 × 10(9) and 1 × 10(10) cells) and the remainder received three doses (1 × 10(10) cells) with interleukin (IL)2 support. Serum cytokines and NLR were measured at multiple time points. The mean NLR for all patients was 13.9 (range 4.8-38.1). NLR increased in four patients following treatment with a mean fold change of 1.9. Serum IL6 levels and NLR fold changes demonstrated a trend towards a positive correlation (r=0.77, P=0.10). Patients with poor CEA responses were significantly more likely to have higher NLR level increases (P=0.048). Increased NLR levels were associated with poor responses following CAR-T HAI. NLR variations and associated cytokine changes may be useful surrogates of response to CAR-T HAI.

Summary box The severe acute respiratory syndrome (SARS) outbreak in 2002/2003,1 which affected 37 countries and resulted in nearly 800 deaths,2 prompted a critical re-think of the global health security architecture. Recognition of the threat posed by emerging infectious diseases (EIDs) and the need to improve national and global surveillance and outbreak response systems motivated the World Health Assembly to adopt the International Health Regulations (IHR) in 2005.3 In the interim, the fateful tsunami of 2004 provided another turning point, emphasising the need for emergency preparedness in order to respond to and recover from major natural disasters. Against this backdrop, WHO’s Western Pacific and South-East Asia regions adopted an all-hazards approach, encompassing disease outbreaks and natural disasters such as cyclones, tsunamis and earthquakes in order to strengthen their health emergency programmes. Despite these constructive developments, most countries faced significant challenges to implement IHR recommendations once the ‘sense of crisis’ passed. The global health security agenda was revived only after the 2014/2015 Ebola virus outbreak in West Africa. Post hoc analyses of the nature and impact of this outbreak, which killed more than 11 000 people, emphasised the contribution of dysfunctional health systems and …

Around 1.3 million tonnes of tropical shrimp are caught annually throughout the world, primarily using bottom trawls. There are many concerns about the sustainability of these catches and the ecosystems impacts of tropical shrimp trawl fisheries. This paper describes ageneric tropical shrimp trawl blueprint for improvement of management which was developed following a global review of tropical shrimp fisheries and consideration of best practice in fisheries management. The generic blueprint is intended for adaptation through stakeholder consultation and workshops in different countries to reflect country-specific needs, and to result in country- or fisheries-specific shrimp trawl management plans. This process of adaptation has already taken place in Suriname, India, Malaysia, and Indonesia. Work in these four countries has affirmed the usefulness of the contents and structure of the generic blueprint, as well as the importance of country-specific adaptations. The adaptation process has also generated a number of important lessons in terms of preparation for the adaptation workshops, their completion, and post-workshop activities. Of particular note is that long-term improvements in sustainability are critically dependent on effective and concerted follow-up after the adaptation workshops to ensure the formal adoption of the management plans by government and their coherence with and incorporation into other national and project planning frameworks and developments.

Since the release of the Bio 2010 report in 2003, significant emphasis has been placed on initiating changes in the way undergraduate biology and mathematics courses are taught and on creating new educational materials to facilitate those changes. Quantitative approaches, including mathematical models, are now considered critical for the education of the next generation of biologists. In response, mathematics departments across the country have initiated changes to their introductory calculus sequence, adding models, projects, and examples from the life sciences, or offering specialized calculus courses for biology majors. However, calculus-based models and techniques from those courses have been slow to propagate into the traditional general biology courses. And although modern biology has generated exciting opportunities for applications of a broad spectrum of mathematical theories, the impact on the undergraduate mathematics courses outside of the calculus/ordinary differential equations sequence has been minimal at best. Thus, the limited interdisciplinary cross-over between the undergraduate mathematics and biology curricula has remained stubbornly stagnant despite ongoing calls for integrated approaches.We think that this phenomenon is due primarily to a lack of appropriate non-calculus-based interdisciplinary educational materials rather than inaccessibility of the essential underlying mathematical and biology concepts. Here we present a module that uses Boolean network models of the lac operon regulatory mechanism as an introduction to the conceptual importance of mathematical models and their analysis. No mathematics background beyond high school algebra is necessary to construct the model, which makes the approach particularly appropriate for introductory biology and mathematics courses. Initially the module focuses on modeling via Boolean logic, Boolean algebra, discrete dynamical systems, and directed graphs. The analysis of the model, however, leads to interesting advanced mathematical questions involving polynomial ideals and algebraic varieties that are beyond the mathematical proficiency of most biology students but are of interest in advanced level abstract algebra courses. These questions can also be used to map a path toward further research-level problems. All computations are carried out by computational algebra systems and the advanced mathematical theory implemented by the software can be covered in detail in abstract algebra courses with mathematics students. Biology students and students in lower level mathematic courses, on the other hand, can view the implementation as a “black box” and focus on the interpretation and the implications of the output.The module is available from the authors for classroom testing and adoption.

We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

Cet article apporte des elements d’information sur les principaux defis auxquels les gouvernements des pays partenaires s’attendent a etre confrontes a un horizon de cinq a dix ans, et sur la facon dont ils pensent qu’evolueront leurs relations avec les fournisseurs d’aide au developpement membres du CAD pour faire face a ces defis. Sur la base des resultats d’une enquete commandee par l’OCDE aupres des gouvernements de 40 pays partenaires en developpement, il en ressort que la cooperation pour le developpement continuera de faire l’objet d’une forte demande etant donne les defis economiques et environnementaux qui se dessinent. Cependant, les pays ayant repondu a l’enquete s’attendent dans les annees qui viennent a ce que les fournisseurs membres du CAD s’affirment davantage en tant que facilitateurs : en continuant a apporter un soutien financier vital, mais a l’appui de programmes d'investissement sectoriels a l’initiative de l’Etat ; en fournissant un soutien technique et des conseils sur l’action a mener de meilleure qualite et plus frequent; et en developpant des initiatives en vue de mobiliser des financements prives. Cet article viendra enrichir la reflexion a laquelle donne lieu le projet de la Direction de la cooperation pour le developpement de l’OCDE « L’organisme d’aide de demain », qui a pour but de determiner de quelle facon les administrations chargees du developpement des membres du CAD devront s’adapter aux defis a venir dans un monde en rapide mutation.

Editor’s Note : These papers are contributions to the ‘Policy Debate’ section of International Development Policy. In this section, academics, policy-makers and practitioners engage in a dialogue on global development challenges. Papers are copy-edited but not peer-reviewed. Instead, the initial thematic contribution is followed by critical comments and reactions from scholars and/or policy-makers. The initial paper takes the form of a structured interview with Inge Kaul, conducted by Graduate Institute Research Fellow Robin Davies, on the topic of Global vs. National Public Goods in the post-2015 international development framework. Kaul argues that for the good of developing countries and the world as whole, support from developed countries for the provision of global public goods (GPGs), such as climate change mitigation and communicable disease surveillance and control, should be conceived as an international extension of their domestic policies. Financing for GPGs constitutes payment for services rendered, not aid. Likewise, primary responsibility for the production of GPGs should rest with issue- and outcome-oriented ‘tsars’ at both the national and global levels, rather than with overstretched treaty- or country-oriented multilateral organisations. It follows from this that the distinction within the SDG framework between global and national goals is not merely one of level, but one of kind. Global goals call for distinctive financing and implementation arrangements. The initial paper is followed two critical comments, (1) by Robert Glasser, Executive-in-Residence, Geneva Centre for Security Policy, and (2) by Michael Gerber, Ambassador and Special Envoy for Global Sustainable Development, Swiss Federal Department of Foreign Affairs with Luca Etter, Policy Advisor at the Swiss Agency for Development and Cooperation (SDC).

This paper provides insights into what partner country governments anticipate will be their main development challenges within five to ten years, and into how they expect their relationships with DAC development assistance providers to evolve in order to meet these challenges. Based on results from an OECD-commissioned survey of 40 developing country governments, it finds that demand for development co-operation will remain strong given the economic and environmental challenges that lie ahead. However, the countries surveyed expect DAC providers to shift to a more enabling role in the coming years: providing vital finance, but in support of government-led sector programmes; delivering more and better technical and policy support; and leveraging more private finance. This paper will inform the OECD Development Co-operation Directorate’s ‘Agency of the Future’ project, which seeks to identify how DAC members’ development administrations will need to adapt in order to be fit for purpose in a rapidly changing world.

Ribonucleic acid (RNA) is a long macromolecule built from nucleotides strung together along a sugar-phosphate backbone. Unlike its double-stranded cousin deoxyribonucleic acid, which twists into a double-helix structure, RNA folds and bonds to itself. Because the three-dimensional structure into which RNA folds determines its cellular function, scientists are very interested in understanding how it folds. The challenge is to predict an RNA’s three-dimensional structure given only its raw primary sequence. We begin this chapter by interpreting this problem in a combinatorial framework, using partial matchings and noncrossing arc diagrams called secondary structures. Next, we take an in-depth tour of two very different approaches to the secondary structure prediction problem. The first method attempts to minimize the free energy using a recursive technique called dynamic programming. The second method arises from the field of computational linguistics—RNA secondary structures are generated using a stochastic context-free grammar. Finally, the chapter concludes with a brief overview of how to extend the RNA combinatorial framework to more complicated structures called pseudoknots.

Long-term investment to drive the adoption of precautionary, adaptive and resilience-building fisheries management measures is urgently required, especially given the financially difficult transition period to reach sustainable fisheries. In this paper a case for investing in the recovery of large marine ecosystems is provided based on the future value of recovered fish stocks. It is argued that the current market-based sustainable seafood movement alone will not affect the scale of change needed and must be complemented by investment in fundamental conservation measures that will lead to the recovery of marine ecosystems and promote long-term sustainable use. A rationale for addressing the economically challenging transition period is provided and the basis of a new financial institution to finance the measures necessary for realising the economic, social and environmental benefits of large-scale fisheries reform is proposed.

Purpose: Chimeric antigen receptor–modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs). Experimental Design: We conducted a phase I trial to test HAI of CAR-T in patients with CEA+ liver metastases. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (108, 109, and 1010 cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (1010 cells × 3) along with systemic IL2 support. Results: Four patients had more than 10 liver metastases, and patients received a mean of 2.5 lines of conventional systemic therapy before enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI, and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range, 19%–48%) from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases. Conclusions: We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted. Clin Cancer Res; 21(14); 3149–59. ©2015 AACR.

Enterprise challenge funds use overseas aid to subsidise private investment in poverty-reducing business ventures in developing countries, where such ventures have good medium-term prospects of commercial viability but would probably have been left on the shelf without subsidies. These funds are viewed with instinctive affection by politicians and international development agencies and have a standard set of characteristics, which we describe. Nevertheless, there is considerable confusion about what international development agencies should be seeking to achieve by means of them, and how. We argue the main source of confusion is a failure to distinguish clearly between what we term enterprise development and business modification objectives, and the rationales and instruments appropriate to each. Enterprise development, in this context, involves reducing risks which impede the establishment or expansion of innovative, poverty-reducing, small- to medium-scale business enterprises. Investment projects should be managed and outcomes assessed on a portfolio basis, without excessive post-financing engagement and with a concentration on certain countries and/or sectors. Business modification, by contrast, involves strengthening incentives for the adoption of poverty-reducing business strategies by established (often multinational) firms, through changes at the margin. Here public subsidies do not reduce risk; rather they provide incentives for firms to take pro-poor investment decisions, and thereby facilitate changes in corporate strategy. In this case, proposals should be solicited from the widest possible field and projects supported should be few, substantial and closely managed. We do not seek to assess claims as to the impact of past and present enterprise challenge funds — the evidence base is too slim — but we argue future such mechanisms are more likely to succeed if they single-mindedly pursue one or the other of the above objectives, and shape themselves accordingly.

International development agencies are increasingly looking to business as a partner in achieving development outcomes. Engaging business in development has become a central plank of many countries’ aid policies. However, the potential of public-private partnerships for development is still largely unrealised. Business and development agencies would benefit from a better understanding of what forms of practical partnership might be constructed, for what purposes and with what likely impact. We propose a new framework for thinking about practical engagement between business and development agencies. It is based, in the first instance, on a distinction between partnerships that increase the development impact of core business activity, and those that contribute to the private provision of public goods. Within this framework we discuss development agencies’ existing involvement in inclusive business ventures, pro-poor supply chain initiatives for internationally-traded products, public-private partnerships for service delivery, and product development partnerships in health. In each of these four areas we provide short case studies and identify a set of issues for further consideration in future work. We close with some observations on cross-cutting issues, including the slenderness of the evidence base in this field, and the fragmentation of existing initiatives. Our main conclusions are three. First, the next generation of enterprise challenge funds should be designed on the basis of a broad evaluation of their predecessors and explicit consideration of a set of issues that we identify. Second, more effective brokerage arrangements, and some flagships, will be needed in order to expand public-private partnerships for service delivery. Third, a comprehensive review of product development partnerships should be undertaken which, among other things, compares them to market-based alternatives.

A colonic adenomatous polyp registry (PR) has been organized at the Roger Williams Medical Center whose main functions are to prevent the occurrence of colorectal cancer (CRC) in the enrollees, to provide a population of subjects for epidemiological and interventional studies, and to provide educational, including dietary, information to subjects and physicians. One hundred four and 202 patients with polyps, originally retrieved from the hospital pathology files, were enrolled in the 1984 and 1987 cohorts, respectively, of whom about 90% were followed for at least three years after polypectomy. Three carcinomas, all Dukes A, were found in the right colon in the follow-up period. New polyps identified in the first three years after polypectomy were generally small tubular adenomas with a greater predilection for the right colon than was found for the index polyps. Risk factors for new polyps included history of previous polyps and, probably, multiple index polyps. The use of colonoscopy for postpolypectomy surveillance increased between 1984 and 1987. About 25% of the subjects in each cohort were either lost to follow-up or received no endoscopic surveillance. On the other hand, some of those who were followed were probably subjected to excessive numbers of procedures. Defects in the PR include inadequacy of personal and family history data, and steady loss of patients during the three to six years after polypectomy. Despite the small size and limited resources of our hospital, its colonic polyp registry has already provided information that may help in the management of patients with this premalignant condition. The more widespread use of securely funded polyp registries would probably reduce the incidence of metachronous CRC in that population and would have significant epidemiological and educational functions.

The Global Sustainability Panel (GSP), formed by UN Secretary-General Ban Ki-moon in August 2010, was asked to think big – to come up with a 'new development paradigm' and mechanisms for putting it into practice. Its product was, among other things, meant to help frame the forthcoming third global conference on environment and development, Rio 20. The imposing precedent for this was Our Common Future, the 1987 report of Gro Harlem Brundtland’s World Commission on Environment and Development. The GSP report, Resilient People, Resilient Planet, inevitably borrows much its content from Brundtland but also exhibits interesting differences. This paper is a selective reflection on what the GSP report adds to, and subtracts from, Brundtland’s bedrock. The comparison is anchored in a discussion of two specific themes: international cooperation and resilience. The first is prominent in Brundtland and largely absent in the GSP report; the second, vice versa. I suggest that much of what is puzzling or unsatisfactory in the GSP report flows from a systematic blindness with respect to the need for policy cooperation between states, and with respect to the uses of the concept of resilience.

This paper provides an overview and summary of the data that demonstrate the effectiveness of a dentifrice containing triclosan/copolymer/fluoride in significantly reducing plaque, calculus, gingivitis, and the onset and progression of periodontitis. The caries-preventive benefit of the triclosan/copolymer/fluoride dentifrice was at least as good as that of a fluoride dentifrice. No evidence of bacterial resistance or the development of pathogenic or opportunistic bacteria was observed.