Targeting the undruggable: immunotherapy meets personalized oncology in the genomic era.

Owing to recent advances in genomic technologies, personalized oncology is poised to fundamentally alter cancer therapy. In this paradigm, the mutational and transcriptional profiles of tumors are assessed, and personalized treatments are designed based on the specific molecular abnormalities relevant to each patient's cancer. To date, such approaches have yielded impressive clinical responses in some patients. However, a major limitation of this strategy has also been revealed: the vast majority of tumor mutations are not targetable by current pharmacological approaches. Immunotherapy offers a promising alternative to exploit tumor mutations as targets for clinical intervention. Mutated proteins can give rise to novel antigens (called neoantigens) that are recognized with high specificity by patient T cells. Indeed, neoantigen-specific T cells have been shown to underlie clinical responses to many standard treatments and immunotherapeutic interventions. Moreover, studies in mouse models targeting neoantigens, and early results from clinical trials, have established proof of concept for personalized immunotherapies targeting next-generation sequencing identified neoantigens. Here, we review basic immunological principles related to T-cell recognition of neoantigens, and we examine recent studies that use genomic data to design personalized immunotherapies. We discuss the opportunities and challenges that lie ahead on the road to improving patient outcomes by incorporating immunotherapy into the paradigm of personalized oncology.

Mathematical problem solving, modelling, applications, and links to other subjects

The paper will consist of three parts. In part I we shall present some background considerations which are necessary as a basis for what follows. We shall try to clarify some basic concepts and notions, and we shall collect the most important arguments (and related goals) in favour of problem solving, modelling and applications to other subjects in mathematics instruction. In the main part II we shall review the present state, recent trends, and prospective lines of development, both in empirical or theoretical research and in the practice of mathematics instruction and mathematics education, concerning problem solving, modelling, applications and relations to other subjects. In particular, we shall identify and discuss four major trends: a widened spectrum of arguments, an increased globality, an increased unification, and an extended use of computers. In the final part III we shall comment upon some important issues and problems related to our topic.

Applied mathematical problem solving, modelling, applications, and links to other subjects

The paper will consist of three parts. In part I we shall present some background considerations which are necessary as a basis for what follows. We shall try to clarify some basic concepts and notions, and we shall collect the most important arguments (and related goals) in favour of problem solving, modelling and applications to other subjects in mathematics instruction. In the main part II we shall review the present state, recent trends, and prospective lines of development, both in empirical or theoretical research and in the practice of mathematics instruction and mathematics education, concerning (applied) problem solving, modelling, applications and relations to other subjects. In particular, we shall identify and discuss four major trends: a widened spectrum of arguments, an increased globality, an increased unification, and an extended use of computers. In the final part III we shall comment upon some important issues and problems related to our topic.

As ouvidorias de saúde pública no Estado do Pará: uma relação dialógica entre governo, medicina e sociedade?

Esta Dissertação tematiza sobre as ouvidorias de saúde pública como um espaço de participação cidadã na gestão administrativa, indagando se acontece uma relação dialógica entre governo, medicina e sociedade, na perspectiva de aproximação da gestão e serviços prestados pela saúde pública, de acordo com a Política de Humanização do SUS. A hipótese norteadora do estudo é a de que com a participação popular, através das ouvidorias, são produzidas transformações nas práticas desempenhadas pelos diferentes atores na configuração das práticas no cuidado em saúde, em aproximação com os princípios e estratégias de Humanização do Sistema Único de Saúde, com capacidade de tensionar os papéis constituídos no contexto biomédico que se constituiu como predominante, a partir dos fins do século XVII. Objetiva identificar as contribuições efetivas da atuação das ouvidorias de saúde pública, na construção e execução de novas práticas da saúde, de acordo com a PNH. Foi desenvolvida em quatro capítulos, que tratam da participação social e da história das ouvidorias de saúde pública, no Brasil, do SUS e da Política de Humanização na Saúde,da pesquisa propriamente dita e as considerações finais. A investigação, com desenho qualitativo e exploratório, visa a conhecer, descrever e compreender a realidade da política de humanização nas instituições de saúde pública no estado do Pará, por intermédio das demandas das ouvidorias em um processo de ampliação de mecanismos democráticos de controle social das políticas públicas de saúde. Entre os resultados alcançados nesta pesquisa, cita-se que as Ouvidorias de Saúde Pública têm o claro compromisso de se tornarem instituições de excelência e cumprirem o seu papel na promoção do diálogo entre o estado, a medicina e a sociedade. Quanto a esse processo colaborar na construção de novas práticas em saúde, não se identificam grandes efetividades, porém, serve como valor simbólico de representatividade de acessibilidade de comunicação e diálogo sem burocracia entre sociedade e gestão pública é significativa. Observa-se a necessidade da gestão da saúde pública, no sentido de se organizar em suas várias instâncias.

PREVALENCE AND DETERMINANTS OF EXCLUSIVE BREASTFEEDING IN THE CITY OF SERRANA, SAO PAULO, BRAZIL

The objective of this cross-sectional and quantitative study was to identify the prevalence and determinants of exclusive breastfeeding among infants less than six months of age in the city of Serrana, Sao Paulo, Brazil in 2009. A validated semi-structured questionnaire was administered to the guardians of the children less than six months of age who attended the second phase of a Brazilian vaccination campaign against polio. Univariate and multivariate analysis presented in odds ratios and confidence intervals was accomplished. Of the total of 275 infant participants, only 29.8% were exclusively breastfed. Univariate analysis revealed that mothers who work outside the home without maternity leave, mothers who did not work outside the home, adolescent mothers, and the use of pacifiers have a greater chance of interrupting exclusive breastfeeding. In the multivariate analysis, mothers who work outside the home without maternity leave are three times more likely to wean their children early. Results provide suggestions for the redirection and planning of interventions targeting breastfeeding.

アジア経済研究所図書館所蔵の統計資料コレクションと開発途上地域の統計事情 : 連載「新興地域の統計事情」を始めるにあたって

アジア経済研究所図書館では，50年以上にわたって開発地域の統計資料を網羅的に収集してきた。本稿では，これら資料の収集方法，コレクションの特色，整備・提供方法を説明するとともに，これまでの蔵書構築等を通じて把握してきた開発途上地域の公式統計の整備・公開状況と最近の動向について報告する。また，国際機関による国際比較統計の編纂状況と近年のオープン・データ政策について簡単に概説する。参考資料として主要な国際機関の統計情報一覧と調べ方ガイドを掲載する。

Adjusting to institutional realities: the 2006 NGO law and its effects on civil society in Russia

Key findings: The paper investigates the impact that the legislative changes of 2006 had on civil society in Russia. This legislation has change the regulatory environment in which civil society actors such as Third Sector Organisations operate. Using the past development of civil society organisations as well as insights about how the institutional environment influences this article illustrates: - the undemocratic nature and motivation of the law and how it exploits the structural weaknesses of civil society - how Third Sector Organisations rationalise and translate the legislative changes into their organisational realities and how this changed or did not change their behaviour - the shift in state-civil society relations away from liberal co-existence into more hierarchical arrangements were Third Sector Organisations are subordinated to the state. These trends have far reaching implications for civil society. The empirical evidence shows that state now manages civil society to meet its own political ends. It also shows that organisations in the field welcome the more engage and directive nature of the Russian state. Why is this important? What does it mean for business or other users? Are there policy implications? The research is important as it shows how Third Sector Organisations have reacted to the legislative changes. Further it provides a basis for interpretation of the potential future development of civil society. Additional it highlights how the continuous process of democratisation in transition economies sometimes might come unstuck. In particular donor agencies will need to consider these trends when disturbing funding to Third Sector Organisations.

Perspectives on gender, migration and transnational work: joint work of social reproduction and care in Southern Europe

This paper presents the "state of the art" and some of the main issues discussed in relation to the topic of transnational migration and reproductive work in southern Europe. We start doing a genealogy of the complex theoretical development leading to the consolidation of the research program, linking consideration of gender with transnational migration and transformation of work and ways of survival, thus making the production aspects as reproductive, in a context of globalization. The analysis of the process of multiscale reconfiguration of social reproduction and care, with particular attention to its present global dimension is presented, pointing to the turning point of this line of research that would have taken place with the beginning of this century, with the rise notions such as "global care chains" (Hochschild, 2001), or "care drain" (Ehrenreich and Hochschild, 2013). Also, the role of this new agency, now composed in many cases women who migrate to other countries or continents, precisely to address these reproductive activities, is recognized. Finally, reference is made to some of the new conceptual and theoretical developments in this area.

The economic situation

This is a quarterly newsletter on the economy written by Senior Fellow Bruce Yandle, Clemson Alumni Distinguished Professor of Economics Emeritus and Interim Dean of Clemson's College of Business & Behavioral Science. The newsletter provides an analysis of national, regional, and state economic trends and activity. Each issue gives an update on GDP growth, interest rate trends, and comments on major events that affect the economic outlook.

The economic situation

This is a quarterly newsletter on the economy written by Senior Fellow Bruce Yandle, Clemson Alumni Distinguished Professor of Economics Emeritus and Interim Dean of Clemson's College of Business & Behavioral Science. The newsletter provides an analysis of national, regional, and state economic trends and activity. Each issue gives an update on GDP growth, interest rate trends, and comments on major events that affect the economic outlook.

The economic situation

This is a quarterly newsletter on the economy written by Senior Fellow Bruce Yandle, Clemson Alumni Distinguished Professor of Economics Emeritus and Interim Dean of Clemson's College of Business & Behavioral Science. The newsletter provides an analysis of national, regional, and state economic trends and activity. Each issue gives an update on GDP growth, interest rate trends, and comments on major events that affect the economic outlook.

The economic situation

This is a quarterly newsletter on the economy written by Senior Fellow Bruce Yandle, Clemson Alumni Distinguished Professor of Economics Emeritus and Interim Dean of Clemson's College of Business & Behavioral Science. The newsletter provides an analysis of national, regional, and state economic trends and activity. Each issue gives an update on GDP growth, interest rate trends, and comments on major events that affect the economic outlook.

The economic situation

This is a quarterly newsletter on the economy written by Senior Fellow Bruce Yandle, Clemson Alumni Distinguished Professor of Economics Emeritus and Interim Dean of Clemson's College of Business & Behavioral Science. The newsletter provides an analysis of national, regional, and state economic trends and activity. Each issue gives an update on GDP growth, interest rate trends, and comments on major events that affect the economic outlook.

The economic situation

This is a quarterly newsletter on the economy written by Senior Fellow Bruce Yandle, Clemson Alumni Distinguished Professor of Economics Emeritus and Interim Dean of Clemson's College of Business & Behavioral Science. The newsletter provides an analysis of national, regional, and state economic trends and activity. Each issue gives an update on GDP growth, interest rate trends, and comments on major events that affect the economic outlook.