Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer.

The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment, using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8). Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor or FLT3 ligand) and costimulation by agonistic α-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. This therapeutic effect was associated with increased proliferation and function of tumor antigen-specific effector CD8(+) T cells, inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of effector T-cell signaling molecules, and generation of T memory precursor cells. Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by reprogramming suppressive and stimulatory signals that yielded more powerful cancer control.

Challenging the "inoffensiveness" of regular cannabis use by its associations with other current risky substance use--a census of 20-year-old Swiss men.

3,537 men enrolling in 2007 for mandatory army recruitment procedures were assessed for the co-occurrence of risky licit substance use among risky cannabis users. Risky cannabis use was defined as at least twice weekly; risky alcohol use as 6+ drinks more than once/monthly, or more than 20 drinks per week; and risky tobacco use as daily smoking. Ninety-five percent of all risky cannabis users reported other risky use. They began using cannabis earlier than did non-risky users, but age of onset was unrelated to other risky substance use. A pressing public health issue among cannabis users stems from risky licit substance use warranting preventive efforts within this age group.

Thermal energetics of the New-Guinean moss-forest rat (Rattus niobe) in comparison with other tropical murid rodents.

The thermal energetics of rodents from cool, wet tropical highlands are poorly known. Metabolic rate, body temperature and thermal conductance were measured in the moss-forest rat, Rattus niobe (Rodentia), a small murid endemic to the highlands of New Guinea. These data were evaluated in the context of the variation observed in the genus Rattus and among tropical murids. In 7 adult R. niobe, basal metabolic rate (BMR) averaged 53.6±6.6mLO2h(-1), or 103% of the value predicted for a body mass of 42.3±5.8g. Compared to other species of Rattus, R. niobe combines a low body temperature (35.5±0.6°C) and a moderately low minimal wet thermal conductance cmin (5.88±0.7mLO2h(-1)°C(-1), 95% of predicted) with a small size, all of which lead to reduced energy expenditure in a constantly cool environment. The correlations of mean annual rainfall and temperature, altitude and body mass with BMR, body temperature and cmin were analyzed comparatively among tropical Muridae. Neither BMR, nor cmin or body temperature correlated with ambient temperature or altitude. Some of the factors which promote high BMR in higher latitude habitats, such as seasonal exposure to very low temperature and short reproductive season, are lacking in wet montane tropical forests. BMR increased with rainfall, confirming a pattern observed among other assemblages of mammals. This correlation was due to the low BMR of several desert adapted murids, while R. niobe and other species from wet habitats had a moderate BMR.

China´s Economic Security Police Towards ASEAN From

After the economic reforms of 1978, China started rising very fast and started engaging other countries in the region which has served to increase its confidence in the region. In the post cold war period, China was seen as a big threat for the region because of its claims on the South China Sea. Nevertheless, this image was eliminated when China engaged ASEAN and other multilateral and regional organizations. This paper is studying China’s economic and security policies towards ASEAN. Globalization Theory is the theory being used to explain the nature of China-ASEAN relations. This research paper argues that China’s rise is promoting peace in the region. With the engagement policy, China started promoting trade and security co operations based on mutual benefits and dialogues for the peaceful resolutions of the disputes in the region. This contributed greatly to improve China’s image in the region. Additionally, China’s posture during the economic crises of 1997 also greatly contributed to improve its image. Thus, the rise of China is providing opportunity to the other countries in East Asia. Chapter One: Background On China-ASEAN Relations The use of Soft Power and engagement policy by the Chinese government has helped to change China’s image in the region. By using these policies China has been able to clear the feeling of suspicion and mistrust among the Asian states. China has increased its participation in multilateral and regional organizations, such as ASEAN. Due to this China has been able to promote economic and security co-operation among countries in the region. Thus, from being a potential threat China became a potential co-operative partner. Chapter Two: A Look into ASEAN ASEAN was originally formed on 8th August 1967 in Bangkok, Thailand, by Indonesia, Malaysia, the Philippines, Singapore and Thailand. Nevertheless, ASEAN was not the first regional group created to act as forum for dialogue between the leaders of different countries. Thought, it is the only one which could work in the region. The aim of the foundation of ASEAN was to promote peace and stability in the Abstract 2 region and also contain the spread of communism in Southeast Asia. For this reason, China did not engage ASEAN until 1990. However, in 1978 with the establishment of the open up policy China started engaging other countries. It started building trust among its neighboring countries by using soft power. By 1992, China formalized its diplomatic ties with ASEAN as a group. The diplomatic ties between China and ASEAN focus on multilateralism and co-operation as the best way for a more peaceful Asia and the search for common security. Thus, security in the region is promoted through economic co-operation among the states. Therefore the relation between China – ASEAN emphasizes the five principles of peaceful coexistence, mutual benefits in economic co-operation, dialogue promoting trust and the peaceful settlement of disputes. Chapter Three: China-ASEAN Economic Relations Since 1978 The economic reform of 1978 has greatly contributed to the economic development of China. After the adoption of the open up policy, China has been able to establish economic and trade relations with the outside world. The realist school of thought had predicted that Asia will not be stable in the post cold war period. Nevertheless, this has not been the case in Asia. China is growing peacefully with the co-operation of countries in the region. China is establishing strong ties with its neighboring countries. China and ASEAN relations focus on mutual benefit instead of being a zero sum game. Thus these relations are aimed at encouraging trust and economic co-operation in the region. China and ASEAN have agreed on Free Trade to assure that the two parties benefit from the co-operation. The ACFTA will have a great impact on economic, political and security issues. This will enable China to increase its influence in Asia and counterbalance the influences that Japan and U.S have in the region. Chapter Four: China ASEAN Relations in the Security Perspective This Chapter is about China and ASEAN relations on security issue. The new security issues of the post cold war period need to be solved in multilateral way. China as a major power in the region, through its engagement policy has solved most Abstract 3 of the disputes in the region using multilateral means. China has also found ways to solve the dispute over Spratly Islands peacefully, through dialogue using ASEAN. Additionally, China signed the Treaty of Amity in 2003, promoted security initiatives through ARF, Declaration on Conduct of Parties in the South China Sea and documents covering non-traditional security threats, economic co-operation and agricultural co-operation in November 2002, and the Joint Declaration on Strategic. Chapter Five: Finding and Analysis This chapter provides a quantitative and qualitative analysis of the date collected throughout this research. It provides an analysis of how the rise of China is promoting peace in the region. China has been promoting mutual beneficial trade and security co-operation which has increased its influence in the region. China has also been able to solve most of the territorial and border dispute in the region through ASEAN. Thus, ASEAN has amended China’s relations with other countries in the region. Therefore, China’s foreign policy in the region has a big impact in shaping the dynamic relations in East Asia. Conclusion and Recommendations This paper concluded that the relationships between China and ASEAN are contributing to peace in the region. After China engaged ASEAN, it has been able to promote multilateral trade based on mutual benefit. This is clearly emphasized by the CAFTA. Additionally, China has solved most of the dispute in the region. It has also found way for a peaceful resolution of the dispute over Spratly Island. Nowadays, the ASEAN countries don’t see China as a threat to the region. Nevertheless, they’ve adopted deterrence measures such as establishing diplomatic relations with other big powers in the region to assure that the region continues to grow peacefully. Concerning this deterrence measures, I recommend as another way for a continued peaceful growth, the resolution of the outstanding dispute.

Health and (other) Asset Holdings

The empirical literature on the asset allocation and medical expenditures of U.S. households consistently shows that risky portfolio shares are increasing in both wealth and health whereas health investment shares are decreasing in these same variables. Despite this evidence, most of the existing models treat financial and health-related choices separately. This paper bridges this gap by proposing a tractable framework for the joint determination of optimal consumption, portfolio and health investments. We solve for the optimal rules in closed form and show that the model can theoretically reproduce the empirical facts. Capitalizing on this closed-form solution, we perform a structural estimation of the model on HRS data. Our parameter estimates are reasonable and confirm the relevance of all the main characteristics of the model.

STRATEGIES TO SURPASS THE VULNERABILITY OF THE SMALL ISLAND STATES WITH FEW RESOURCES: THE CASE OF CAPE VERDE

The problem of small Island Developing States (SIDS) is quite recent, end of the 80s and 90s, still looking for a theoretical consolidation. SIDS, as small states in development, formed by one or several islands geographically dispersed, present reduced population, market, territory, natural resources, including drinkable water, and, in great number of the cases, low level of economic activity, factors that together, hinder the gathering of scale economies. To these diseconomies they come to join the more elevated costs in transports and communications which, allies to lower productivities, to a smaller quality and diversification of its productions, which difficult its integration in the world economy. In some SIDS these factors are not dissociating of the few investments in infrastructures, in the formation of human resources and in productive investments, just as it happens in most of the developing countries. In ecological terms, many of them with shortage of natural resources, but integrating important ecosystems in national and world terms, but with great fragility relatively to the pollution action, of excessive fishing, of uncontrolled development of tourism, factors that, conjugated and associated to the stove effect, condition the climate and the slope of the medium level of the sea water and therefore could put in cause the own survival of some of them. The drive to the awareness of the international community towards its problems summed up with the accomplishment by the United Nations in the Barbados’s Conference, 1994 where the right to the development was emphasized, through the going up the appropriate strategies and the Programme of Action for the Sustainable Development of the SIDS. The orientation of the regional and international cooperation in that sense, sharing technology (namely clean technology and control and administration environmental technology), information and creation of capacity-building, supplying means, including financial resources, creating non discriminatory and just trade rules, it would drive to the establishment of a world system economically more equal, in which the production, the consumption, the pollution levels, the demographic politics were guided towards the sustainability. It constituted an important step for the recognition for the international community on the specificities of those states and it allowed the definition of a group of norms and politics to implement at the national, regional and international level and it was important that they continued in the sense of the sustainable development. But this Conference had in its origin previous summits: the Summit of Rio de Janeiro about Environment and Development, accomplished in 1992, which left an important document - the Agenda 21, in the Conference of Stockholm at 1972 and even in the Conference of Ramsar, 1971 about “Wetlands.” CENTRO DE ESTUDOS AFRICANOS Occasional Papers © CEA - Centro de Estudos Africanos 4 Later, the Valletta Declaration, Malta, 1998, the Forum of Small States, 2002, get the international community's attention for the problems of SIDS again, in the sense that they act to increase its resilience. If the definition of “vulnerability” was the inability of the countries to resist economical, ecological and socially to the external shocks and “resilience” as the potential for them to absorb and minimize the impact of those shocks, presenting a structure that allows them to be little affected by them, a part of the available studies, dated of the 90s, indicate that the SIDS are more vulnerable than the other developing countries. The vulnerability of SIDS results from the fact the they present an assemblage of characteristics that turns them less capable of resisting or they advance strategies that allow a larger resilience to the external shocks, either anthropogenic (economical, financial, environmental) or even natural, connected with the vicissitudes of the nature. If these vulnerability factors were grouped with the expansion of the economic capitalist system at world level, the economic and financial globalisation, the incessant search of growing profits on the part of the multinational enterprises, the technological accelerated evolution drives to a situation of disfavour of the more poor. The creation of the resilience to the external shocks, to the process of globalisation, demands from SIDS and of many other developing countries the endogen definition of strategies and solid but flexible programs of integrated development. These must be assumed by the instituted power, but also by the other stakeholders, including companies and organizations of the civil society and for the population in general. But that demands strong investment in the formation of human resources, in infrastructures, in investigation centres; it demands the creation capacity not only to produce, but also to produce differently and do international marketing. It demands institutional capacity. Cape Verde is on its way to this stage.

Recurrent stroke predictors differ in medically treated patients with pathogenic vs. other PFOs.

OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score. METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of ≤6 points, n = 677). We tested 15 clinical, 5 radiologic, and 3 echocardiographic variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant. RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group. CONCLUSION: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

The Harsh Fight against Poverty in Sao Tome and Principe

post-independence, and on the other hand, the testimonies from Sao Tomeans individuals from different social conditions and different degrees of political responsibility, this article approaches some possible connections between poverty and micro-violence in Sao Tome and Principe. It is offered an outline of research for the difficulties of the eradication of poverty and, concomitantly, the diffusion of a growing feeling of social disruption, processes in all contrary to the promises of independence for this archipelago. Frequently, the archipelago’s visitors make hasty opinions about the imaginary effortlessness of governing two islands with less than one hundred and fifty thousand citizens. However, contrary to this very common prejudice, the micro-insularity is considered an obstacle to development, a notion shared by many Sao Tomeans. Could micro-insularity equally be, under this outlook, an impoverishment-inducing factor? Regarding the development, there is some truth in this diagnosis, which the Sao Tomeans also use to justify their current difficulties. Throughout the 70s and 80s, the MLSTP – Movimento de Libertação de São Tomé e Príncipe (Movement for the Liberation of Sao Tome and Principe) endorsed a development founded on an expansion of cacao cultures, at the expenses of an intensified production rate, and on an incipient industrialization, which was intended to avoid importations and economic dependency. At the time, the Sao Tomeans leaders justified the rising daily difficulties, quite the opposite of the promises made during the independence, with an economic disarticulation resulting from the gradual abandonment of economic infrastructures inflicted by the last batch of colonists, which affected the cacao plantations too. Simultaneously, both the inefficiency and cost of the industrial endeavors launched after the independence and the erosion of labor and social relationships in nationalized farms had been rather neglected.

Evolução Demográfica da Ilha de São Vicente do Descobrimento a 1950

Este trabalho propõe-se analisar a evolução demográfica da ilha de São Vicente, desde o seu descobrimento até 1950. A análise é complementada pelo estudo da natalidade e mortalidade desta ilha que, à semelhança do resto do arquipélago, foi marcada histórica e demograficamente por cíclicas crises de mortalidade e uma elevada natalidade. As particularidades da ilha prendem-se com o seu povoamento tardio e com a sua ligação ao Porto Grande que lhe deu uma dinâmica diferente do resto do país. A pesquisa foi desenvolvida nos arquivos da Conservatória do Registo Civil de São Vicente e da Câmara Municipal de São Vicente. The present work aims at analysing the demographic evolution on the island of S. Vicente since its discovery till 1950, being the analysis complemented by a study on birth and mortality rates on this island. Similarly to the other islands, these rates were marked, both historically and demographically, by recurrent mortality crises, as well as by high birth-rate. The island particularities not only result from its late settlement, but also from its close relationship with the “Porto Grande” harbour, which conferred it a different dynamic, if compared to other parts of this country. This research was based on the files recorded at the Registry Office and the Town-Hall, both in S. Vicente.

O papel dos Portos no Desenvolvimento da Economia de Cabo Verde

Os Portos de Cabo Verde sempre tiveram um papel importante no desenvolvimento económico e social, isto porque facilitam a deslocação de pessoas e mercadorias entre as ilhas, de igual forma que contribuem para a minimização dos efeitos da descontinuidade territorial, facilitando a transferência de produtos e pessoas a um menor custo. É nesse contexto que o tema desenvolvido se justifica pelo impacto que a actividade portuária tem na economia de Cabo Verde. O Capítulo I faz uma abordagem sobre a Administração Portuária em Cabo Verde, onde se relata uma breve resenha histórica dos portos nacionais, o estilo da Autoridade Portuária e o papel do Estado no Sector Portuário, bem como os serviços prestados pelos Portos de Cabo Verde. O Capítulo II refere-se sobre o papel do Sector Portuário no desenvolvimento socioeconómico de Cabo Verde, no qual fez-se a caracterização desse Sector, o destaque da contribuição dos Portos no desenvolvimento do país e a ilustração do grau de importância do comércio externo na economia nacional. Ainda nesse Capítulo, fez-se referência à Segurança Portuária como sendo um elemento fundamental para o desenvolvimento económico dos Portos de Cabo Verde e destacou-se as Estratégias de Marketing que a Enapor vem adoptando como instrumento de Gestão para vender a imagem da Empresa. O 3º e último Capítulo enfatiza a relevância do Porto Grande, um dos portos principais que apresenta a melhor infra-estrutura portuária de Cabo Verde. Destacou-se o efeito económico provocado pela actividade portuária na economia regional, o estágio de desenvolvimento da cidade do Mindelo, como consequência da evolução do Porto Grande, e ainda salientou-se a localização geográfica do Porto Grande em relação aos portos dos países limítrofes. Por último, fez-se uma análise SWOT, tendo-se destacado os principais pontos fortes do Porto e realçando algumas perspectivas futuras, tendo em conta os desafios que a Administração do Porto, como entidade gestora, persegue.The Cape Verdean Ports have always had an important role in economic and social development as they facilitate the transfer of people and merchandise among the islands. The same way they reduce the effect of territorial discontinuity, facilitating the transfer of cargo and people at low costs. Thus the addressed theme is justified by the impel Port activities provide to the economy in Cape Verde. This work is divided into three chapters: Chapter one introduces the Ports Administration in Cape Verde and a short history overview is set up on the topic. The management method and or the role of the National Govern concerning the port sector as well the services offered by these Ports are also stated. Chapter two refers to the role of the Port Sector in the socio-economic developing process in Cape Verde and some characteristics concerning this Sector. Emphasis is put on the contribution the Ports provide to the development of the country and the great importance of the extern trade in national economy. In addition, this chapter deals with port security as an essential factor to economic development of the Cape Verdean Ports. Marketing strategies adopted by ENAPOR as managing instruments in order to put on the market a good image of the enterprise is also addressed. Chapter three brings in the relevance of Porto Grande, one of the main Ports in Cape Verde which in fact has the best infrastructures. The effect on regional economy by the activities of the Port and the development moment in Mindelo city is considered as consequence of Porto Grande progress. The geographic location of the harbour and other harbours in near countries is also studied. Finally, a SWOT analysis is introduced, the main strong points as well some future prospective considering challenges of the harbour are pointed out.

How geographic distance and depth drive ecological variability and isolation of demersal fish communities in an archipelago system (Cape Verde, Eastern Atlantic Ocean)

Cape Verde is a tropical oceanic ecosystem, highly fragmented and dispersed, with islands physically isolated by distance and depth. To understand how isolation affects the ecological variability in this archipelago, we conducted a research project on the community structure of the 18 commercially most important demersal fishes. An index of ecological distance based on species relative dominance (Di) is developed from Catch Per Unit Effort, derived from an extensive database of artisanal fisheries. Two ecological measures of distance between islands are calculated: at the species level, DDi, and at the community level, DD (sum of DDi). A physical isolation factor (Idb) combining distance (d) and bathymetry (b) is proposed. Covariance analysis shows that isolation factor is positively correlated with both DDi and DD, suggesting that Idb can be considered as an ecological isolation factor. The effect of Idb varies with season and species. This effect is stronger in summer (May to November), than in winter (December to April), which appears to be more unstable. Species react differently to Idb, independently of season. A principal component analysis on the monthly (DDi) for the 12 islands and the 18 species, complemented by an agglomerative hierarchical clustering, shows a geographic pattern of island organization, according to Idb. Results indicate that the ecological structure of demersal fish communities of Cape Verde archipelago, both in time and space, can be explained by a geographic isolation factor. The analytical approach used here is promising and could be tested in other archipelago systems.