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Caenorhabditis elegans embodies the expectations of a solution-driven take on biology on the one hand, and the mysteries and wonders of life that drives biologists to go to their labs on the other hand.

Regulatory agencies installed orphan drug regulations to stimulate research and development of new innovative treatments for life-threatening diseases with a low prevalence (rare diseases). We established a list of well-known food-related ingredients with clinical evidence for rare diseases in the open medical literature that obtained marketing authorization as an expensive "orphan drug", protected by intellectual property (IP) rights. We show that these ingredients are part of an established practice of medicinal compounding-a form of point of care manufacturing. We argue that these ingredients should be considered as "pharmaceutical commons", and that regulatory incentives for private companies and market protection mechanisms such as IP rights are not justified in this case. ispartof: FRONTIERS IN PHARMACOLOGY vol:12 ispartof: location:Switzerland status: published

Observing voices claim that times are troubling, when they really mean that times are interesting Interesting to analyse society when it supposedly lays bare its hidden structures

What is sustaining the divide between nature and nurture, even though sciences like epigenetics have been challenging it for at least two decades? Evelyn Fox Keller asked this question and considered it a logical problem rooted in terminological confusion within the sciences. In this article, we propose a complementary diagnosis of the problem: the nature-nurture divide is (re-)mobilized when society faces questions of inclusion and solidarity. With examples stemming from the fields of insurance and health care, immigration policy and epigenetics, we demonstrate how the nature-nurture divide is performed through techniques of classification for a politics of solidarity. We identify a common operation to these different examples that we coin 'biopolitical imputation'. We use this term to draw attention to how (Western) societal institutions, including science, create solvable problems out of complex situations, defining human actors and their agency along the lines of the nature-nurture divide as a moral guide. We argue that the tenacity of the nature-nurture divide is therefore not only a logical problem needing better scientific concepts, but also a cosmopolitical problem asking for a more profound reflection on the ontology and ethics of solidarity in order to move beyond the biopolitics of nature versus nurture. ispartof: Health vol:24 issue:2 pages:203-219 ispartof: location:England status: Published online

Single-index models are popular regression models that are more flexible than linear models and still maintain more structure than purely nonparametric models. We consider the problem of estimating the regression parameters under a monotonicity constraint on the unknown link function. In contrast to the standard approach of using smoothing techniques, we review different "non-smooth" estimators that avoid the difficult smoothing parameter selection. For about 30 years, one has had the conjecture that the profile least squares estimator is an n-consistent estimator of the regression parameter, but the only non-smooth argmin/argmax estimators that are actually known to achieve this n-rate are not based on the nonparametric least squares estimator of the link function. However, solving a score equation corresponding to the least squares approach results in n-consistent estimators. We illustrate the good behavior of the score approach via simulations. The connection with the binary choice and current status linear regression models is also discussed. Research Foundation Flanders (FWO), Grant/Award Number: 11W7315N; IAP Research Network P7/06 of the Belgian State (Belgian Science Policy); VSC-Flemish Supercomputer Center, funded by the Hercules Foundation and the Flemish Government-department EWI

© 2018, © 2018 Process Press. In the EU today, health claims on food labels are regulated as a form of information. Before the 2000s, statements referring to health on packaged food were subject to different national regulations across the EU, with different perspectives on where the boundary lies between food and drugs. The turn to more horizontal legislation in EU food law and increased emphasis on the role of information for the functioning of the Single Market does not in itself explain why, and especially how, health-related statements on food products have been turned into information and what consequences this has produced. Construction of such a European ‘technological zone’, where health claims circulate as a form of information, can be understood as ‘information's constitutive outside’ (Barry, A. (2006) Technological zones, European Journal of Social Theory, 9(2), pp. 239–253; Barry, A. (2013) Material Politics: Disputes along the Pipeline (Oxford: Wiley-Blackwell)). This outside hinges on techno-political discussion, lobbying and decisions where the boundary between health and disease is at stake, along with food's materiality. The concept of referential displacement shows how decisions in the regulatory process have transformed controversial references to human health on food labels into ‘health claims’ as an informational category by shifting the relation between the health claim and its material referents: food itself, health and the body. Referential displacement produces a new kind of information that implies similar efficacy to pharmaceutical drugs, without interfering with the zone or market of pharmaceuticals. ispartof: Science As Culture vol:28 issue:4 pages:427-448 status: published

BACKGROUND: As increasing numbers of dengue vaccines and therapeutics are in clinical development, standardized consensus clinical endpoint definitions are urgently needed to assess the efficacy of different interventions with respect to disease severity. We aimed to convene dengue experts representing various sectors and dengue endemic areas to review the literature and propose clinical endpoint definitions for moderate and severe disease based on the framework provided by the WHO 2009 classification. METHODS: The endpoints were first proposed and discussed in a structured expert consultation. After that, the Delphi method was carried out to assess the usefulness, validity and feasibility of the standardized clinical disease endpoints for interventional dengue research. RESULTS: Most respondents (> 80%) agreed there is a need for both standardized clinical endpoints and operationalization of severe endpoints. Most respondents (67%) felt there is utility for moderate severity endpoints, but cited challenges in their development. Hospitalization as a moderate endpoint of disease severity or measure of public health impact was deemed to be useful by only 47% of respondents, but 89% felt it could bring about supplemental information if carefully contextualized according to data collection setting. Over half of the respondents favored alignment of the standard endpoints with the WHO guidelines (58%), but cautioned that the endpoints could have ramifications for public health practice. In terms of data granularity of the endpoints, there was a slight preference for a categorical vs numeric system (e.g. 1-10) (47% vs 34%), and 74% of respondents suggested validating the endpoints using large prospective data sets. CONCLUSION: The structured consensus-building process was successful taking into account the history of the debate around potential endpoints for severe dengue. There is clear support for the development of standardized endpoints for interventional clinical research and the need for subsequent validation with prospective data sets. Challenges include the complexity of developing moderate disease research endpoints for dengue. ispartof: BMC MEDICAL RESEARCH METHODOLOGY vol:18 issue:1 ispartof: location:England status: published

We consider P-spline smoothing in a varying coefficient regression model when the response is subject to random right censoring.We introduce two data transformation approaches to construct a synthetic response vector that is used in a penalized least squares optimization problem. We prove the consistency and asymptotic normality of the P-spline estimators for a diverging number of knots and show by simulation studies and real data examples that the combination of a data transformation for censored observations with P-spline smoothing leads to good estimators of the varying coefficient functions. The research of the first author was supported by the Research Foundation Flanders (FWO) (Grant No. 11W7315N). Support from the IAP Research Network P7/06 of the Belgian State (Belgian Science Policy) is gratefully acknowledged. For the simulations, we used the infrastructure of the VSC - Flemish Supercomputer Center, funded by the Hercules Foundation and the Flemish Government - department EWI.

In this theoretical research article, we develop a new approach towards the implications of the nature/nurture debate for our understanding of responsibility and solidarity. More specifically, we will consider how new (epi-)genetic information may prompt us to rethink these notions. Our starting point is Evelyn Fox Keller’s important book The Mirage of a Space between nature and nurture. While scientists are wondering whether the nature/nurture distinction is still tenable, Keller’s main question is already a step ahead of such considerations: in view of the fact that the nature/nurture distinction is no longer tenable, why do we keep thinking in those terms? To us, this is an important sociological question. We do not agree, however, with Keller’s answer to that question, and this requires us to discuss the moral and political stakes of the nature/nurture distinction. With examples from insurance, healthcare and migration policy, we show how certain societal institutions implicitly draw upon the nature/nurture distinction to determine who is to be included into organized systems of solidarity. Next, we argue that moving beyond the nature/nurture division requires us to rethink our notions of responsibility and solidarity in society, including the sciences. We give examples from the field of epigenetics. Aligning with thinkers such as Bruno Latour, Isabelle Stengers and Donna Haraway, we characterize the step beyond nature and nurture as a speculative and cosmopolitical challenge. In so doing, this article develops a political-ontological or cosmopolitical perspective on questions concerning responsibility and solidarity in the postgenomic age.

It has been proved that direct bootstrapping of the nonparametric maximum likelihood estimator (MLE) of the distribution function in the current status model leads to inconsistent confidence intervals. We show that bootstrapping of functionals of the MLE can however be used to produce valid intervals. To this end, we prove that the bootstrapped MLE converges at the right rate in the $L_p$-distance. We also discuss applications of this result to the current status regression model., Comment: 39 pages, 11 figures

La gouvernance de l’État belge est caractérisée par un double processus de reconfiguration : vers le haut, par les dynamiques d’européanisation, et vers le bas, par un processus de régionalisation approfondi. Par exemple, le domaine de l’environnement est aujourd’hui régionalisé, mais de nombreuses décisions sont prises au niveau de l’Union européenne, dont les instances décisionnelles n’intègrent pas pleinement le fait régional. Cet article s’appuie sur une étude menée auprès des instances fédérales et régionales chargées de la gestion de la qualité de l’air en Belgique. La traduction du cadre européen demanderait le déploiement d’une approche transversale environnement-santé associant tous les niveaux de pouvoir, mais les répondants dénoncent l’absence d’intégration de ces politiques aux niveaux régional et fédéral. Chaque niveau de pouvoir développe une dynamique propre pour réinterpréter la politique et les instruments définis au niveau européen., Governance in Belgium is characterized by a two-fold process ofreconfiguration – i.e., at the upper levels by the dynamics of“Europeanization” and at the lower levels by intensiveregionalization. For example, today the environmental sector isregionalized, but numerous decisions are made at the level of theEuropean Union, whose policymaking authorities have not fully accountedfor regional entities. This article is based on a study conducted amongthe federal and regional authorities responsible for managing airquality in Belgium. Translating the EU framework into action wouldrequire the deployment of a cross-cutting, environment/health approachbringing together all levels of power. At the same time, however, ourrespondents decry the lack of integration of these policies at theregional and federal levels. Each level of power has been developingits own dynamic for reinterpreting policy and instruments defined atthe European level.

The bioeconomy is a strategic program strongly promoted within OECD countries. This paper discusses an example of how the purposes and promises of the bioeconomy are enacted in Brazil, in line with local environmental and political specificities. We focus on scientific and political discourse portraying a technological solution to tackle dengue disease as a public health problem. The technology involves genetically modified mosquitoes that are released into the environment in order to suppress populations of disease-carrying mosquitoes. We show how the promise of tackling dengue, through technical and scientific arguments, becomes connected to political discourse about the welfare and ‘progress’ of Brazil as a nation. We argue that this connection comes about through two types of rhetoric devices that downplay risk and uncertainties in favor of the promises inscribed in laboratory-bred mosquitoes. In line with a basic tenet in the field of Science and Technology Studies, it becomes clear that science and politics are intertwined in both discourse and practice. In addition, we highlight the experimental and political character of public health interventions from a spatial perspective. The mosquitoes are set free in an environment that is considered a natural environment while at the same time responding to certain laboratory conditions such as relative isolation. In addition, the genetically modified mosquitoes, as bio-objects, are expected to act like natural mosquitoes in the wild. With these types of proximity between technology and nature in mind, we argue that the mosquitoes are meant not only to enact the pest management program they have been designed for, but also a political program claiming an avant-garde position of Brazil in a global bioeconomy.

This special issue explores cases from Latin American countries, studied in comparison to global trends in the arenas of public participation, scientific knowledge production, regulation and governance. The authors demonstrate the complexity of these cases, both in terms of regional differences and the different spaces of public, policy, and scientific knowledge production into which such innovations are inserted. The articles are based on rich empirical data collected in Argentina, Brazil, Chile and Paraguay. Authors show that the top-down circulation of policy narratives on biotechnology is challenged, complemented and even partly undermined by local bottom-up dynamics. Conversely, articles also focus on those grassroots dynamics and the ways they are influenced and conditioned by macro-sociological and political-economic factors. Lastly, a great deal of attention is paid to the ways states and national actors actively contribute to their own insertion in globalized markets where bioengineered living resources are increasingly tasked with solving the most pressing economic and social issues. We believe that this collection of works challenges scholars, intellectuals, policy-makers and relevant stakeholders to open up their views of biotechnology as a dynamic construct that interacts with local situations in a variety of ways. ispartof: Technology in Society vol:35 issue:2 pages:75-78 status: published

We discuss a new way of constructing pointwise confidence intervals for the distribution function in the current status model. The confidence intervals are based on the smoothed maximum likelihood estimator (SMLE) and constructed using bootstrap methods. Other methods to construct confidence intervals, using the non-standard limit distribution of the (restricted) MLE, are compared to our approach via simulations and real data applications., 31 pages, 10 figures, 1 table

Air pollution is a systemic risk embedded in environmental, political, social and economic systems. Risk assessments on air pollution therefore involve communication between several stakeholders at multiple scale levels. This study focuses on a small part of the risk assessment, evaluating actions or decisions on both policy and research fields using an importance-performance/feasibility analysis as a scoring methodology. Subsequently, results were discussed by researchers and policy makers at a closed workshop to guarantee a safe place for knowledge integration. Learned aspects and new insights are useful for future scenarios on air pollution. This study was performed in Flanders, the European hot spot for air particulate matter. After 10 years of policy efforts in Flanders, the daily air particulate matter PM10 standard, which was enforced by the European Commission (EC) in 1999, is still being exceeded more times than allowed. No exemption for not achieving this standard was granted by the EC. What went wrong on policy and research fields in Flanders and how can this situation be prevented in the future taking into account the new PM2.5 standard that will be implemented in 2015 (European Directive 2008/50/EC)? Results of the importance-performance/feasibility analysis on actions related to PM research and policy in Flanders and discussions at the workshop, improving the communication between researchers and governmental stakeholders, are looked at.

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials., Author summary Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective, and early recognition of severe dengue and timely supportive care remain the only means to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding deployment of such vaccines or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers, vaccine developers, and public health specialists to develop endpoints. After two working group meetings and discussions at international meetings, the Delphi methodology was used to clarify and further develop endpoints such that 70% or greater agreement was reached on most endpoint definitions including moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. The process identified areas for further evaluation and standardization within the context of ongoing clinical studies. The endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is a tool that we developed thru refinement of previous similar iterations in an attempt to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness. The tool is designed to capture an individual’s overall disease experience based on how the totality of their symptoms impacts their general wellness and daily functionality. We applied the DII to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The card was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the tool in clinical dengue research. There was overall agreement that the tool would generate useful data and provide an alternative perspective to the assessment of drug or vaccine candidates, which in the case of vaccines, are assessed by their reduction in any virologically confirmed dengue of any severity with a focus on the more severe. The DIC needs to be evaluated in the field in the context of vaccine or drug trials, prospective cohort studies, or during experimental human infection studies. Here, we present the final DIC resulting from the Delphi process and offer its further development or use to the dengue research community., Author summary The Dengue Illness Index (DII) is a tool that was developed to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness by capturing the overall subjective disease experience of an individual based on how the totality of their symptoms impacts their wellness and daily functionality. The DII was applied to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The resulting DIC was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the card in dengue research. Here, we report on the Delphi results and present the final DIC.

Lionel Larque et Dominique Pestre dirigent un tres bel ouvrage sur les sciences en societe. L'un vient de la societe civile et des milieux de l'education populaire, l'autre est un historien des sciences chevronne. C'est donc a la croisee entre les enjeux portes par les milieux associatifs, dont il porte les questionnements et les problematiques, et les instruments de la reflexion academique, qui en font la rigueur et la clarte analytique, que se situe cet ouvrage tres foisonnant. Ce dernier d...

This article explores the merits of foregrounding the dichotomy of politicization vs de-politicization for our understanding of bio-objects in order to study their production,circulation, and governance in European societies.By asking how bio-objects are configured in science, policy, public,and media discourses and practices,we focus on the role ofsocio-technical configurations in generating political relations. The bio-object thereby serves as an entry point to approach and conceptualize>the political>in an innovative way.Drawing from our previous work, which uses the concepts of de-politicization and (re-)politicization, this paper puts forward a research agenda for studying the political relations generated by specific socio-technical configurations of bio-objects.