Towards better Olympic accountability

Ten years after the corruption scandal that shook the International Olympic Committee (IOC) in 1999, this article presents the current situation regarding accountability for this non-governmental organization based in Switzerland. The IOC is responsible for ensuring that the Olympic Games are held regularly, and since its foundation has endeavoured to promote sport without discrimination in service of sustainable human development and a better world. Olympic accountability is examined by means of four facets within a theoretical framework. The analysis of each of them shows that although considerable progress has been made by the IOC since 1999, improvements regarding accountability remain both possible and desirable. A mechanism for making improvements is proposed in the Conclusion.

Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort.

BACKGROUND: There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. METHODS: Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. RESULTS: 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). CONCLUSION: Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.

Coexpression of the T-cell receptor constant alpha domain triggers tumor reactivity of single-chain TCR-transduced human T cells.

Transfer of tumor antigen-specific T-cell receptors (TCRs) into human T cells aims at redirecting their cytotoxicity toward tumors. Efficacy and safety may be affected by pairing of natural and introduced TCRalpha/beta chains potentially leading to autoimmunity. We hypothesized that a novel single-chain (sc)TCR framework relying on the coexpression of the TCRalpha constant alpha (Calpha) domain would prevent undesired pairing while preserving structural and functional similarity to a fully assembled double-chain (dc)TCR/CD3 complex. We confirmed this hypothesis for a murine p53-specific scTCR. Substantial effector function was observed only in the presence of a murine Calpha domain preceded by a TCRalpha signal peptide for shuttling to the cell membrane. The generalization to a human gp100-specific TCR required the murinization of both C domains. Structural and functional T-cell avidities of an accessory disulfide-linked scTCR gp100/Calpha were higher than those of a dcTCR. Antigen-dependent phosphorylation of the proximal effector zeta-chain-associated protein kinase 70 at tyrosine 319 was not impaired, reflecting its molecular integrity in signaling. In melanoma-engrafted nonobese diabetic/severe combined immunodeficient mice, adoptive transfer of scTCR gp100/Calpha transduced T cells conferred superior delay in tumor growth among primary and long-term secondary tumor challenges. We conclude that the novel scTCR constitutes a reliable means to immunotherapeutically target hematologic malignancies.

Iowa Department of Transportation Major Items - Preliminary Quantity Report, May 20, 2014; With Addendums

Weekly letting report.

Variabilidad temporal de algunas propiedades químicas en un suelo sometido a distintas sucesiones de cultivo

El presente trabajo ha sido realizado en la Finca Experimental "La Poveda" en Arganda del Rey (Madrid), con las siguientes coordenadas geográficas: latitud 40º19' N; longitud 3º19' W Gr; y altitud 550 m. El objetivo principal consiste en el estudio de la variabilidad temporal de algunas propiedades químicas en un suelo sometido a distintas sucesiones de cultivo. Para el estudio de la variabilidad temporal de las características químicas el muestreo se realizó en los meses de febrero y septiembre de 1993 y febrero y septiembre de 1994. La materia orgánica del sistema Prado/Veza-Avena presenta el menor coeficiente de variación con respecto a los sistemas monocultivo de Cebada y Veza-Avena/Girasol. El menor contenido de materia orgánica a lo largo del tiempo lo presenta el sistema Cebada/Cebada. Los sistemas Prado/Veza-Avena y Veza-Avena/Girasol presentaron contenidos de materia orgánica 42,86% y 40,54% superiores al del sistema Cebada/Cebada.

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Religious diversity is often captured in "mapping studies" that use mostly qualitative methods in order to map and assess the religious communities in a given area. While these studies are useful, they often present weaknesses in that they treat only limited geographic regions, give limited possibilities of comparing across religious groups and cannot test theories. In this chapter, we show how a census and a quantitative National Congregations Study (NCS) methodology can be combined in order to map and assess the religious diversity of a whole country (Switzerland), overcoming the problems mentioned above. We show the methodological steps and selected results concerning organizational, geographic, structural, and cultural diversity.

Clones promissores de seringueira para a região do Vale do Ribeira, São Paulo

Este trabalho objetivou apresentar resultados da primeira seleção de clones de seringueira (Hevea brasiliensis (Willd. ex Adr. de Juss.) Muell.Arg.) da série IAC 300, e amazônicos das séries IAN e Fx, em experimento de pequena escala, visando produção, crescimento e resistência ao mal-das-folhas. A produção e o vigor de 20 clones foram avaliados por dois e nove anos, respectivamente, em PariqüeraAçú, no Vale do Ribeira, SP. Os clones IAC 301, IAC 304, IAC 306 e IAC 319 produziram satisfatoriamente nos dois primeiros anos de sangria. Os clones amazônicos IAN 6323, Fx 3864 e IAN 2903, com produções de 1.078 kg, 945 kg e 900 kg/ha/ano, respectivamente, foram superiores à testemunha IAN 873 (878 kg/ha/ano). Os clones selecionados apresentaram crescimento vigoroso, com extremos de perímetro do caule, na abertura do painel, de 37,40 cm (IAN 4493) a 53,75 cm (IAN 6323), e percentual de plantas aptas à sangria de 7,0% (IAN 4493) a 100% (IAN 6323 e IAC 302), exceto os clones Fx 3899 e IAN 3044. O IAC 315, com 7,37 mm, mostrou maior espessura de casca virgem que o IAN 873 (6,44 mm). Os clones IAC 320, IAC 306 e IAC 315 foram os mais resistentes ao Microcyclus ulei.

Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours.

AIM: Total imatinib concentrations are currently measured for the therapeutic drug monitoring of imatinib, whereas only free drug equilibrates with cells for pharmacological action. Due to technical and cost limitations, routine measurement of free concentrations is generally not performed. In this study, free and total imatinib concentrations were measured to establish a model allowing the confident prediction of imatinib free concentrations based on total concentrations and plasma proteins measurements. METHODS: One hundred and fifty total and free plasma concentrations of imatinib were measured in 49 patients with gastrointestinal stromal tumours. A population pharmacokinetic model was built up to characterize mean total and free concentrations with inter-patient and intrapatient variability, while taking into account α1 -acid glycoprotein (AGP) and human serum albumin (HSA) concentrations, in addition to other demographic and environmental covariates. RESULTS: A one compartment model with first order absorption was used to characterize total and free imatinib concentrations. Only AGP influenced imatinib total clearance. Imatinib free concentrations were best predicted using a non-linear binding model to AGP, with a dissociation constant Kd of 319 ng ml(-1) , assuming a 1:1 molar binding ratio. The addition of HSA in the equation did not improve the prediction of imatinib unbound concentrations. CONCLUSION: Although free concentration monitoring is probably more appropriate than total concentrations, it requires an additional ultrafiltration step and sensitive analytical technology, not always available in clinical laboratories. The model proposed might represent a convenient approach to estimate imatinib free concentrations. However, therapeutic ranges for free imatinib concentrations remain to be established before it enters into routine practice.

08019-011 Staff Beaver Creek Final Report

Staff and Beaver Creeks are two tributaries of the Upper Iowa River (UIR). Additional acres that drain directly into the UIR bring the size of the project area to 41,328 acres. The goal of the project is to reduce sediment loading and excess nutrients from reaching the streams which ultimately reach the UIR. Staff/Beaver Water Quality Project initially received funding as part of the FY 2005 WSPF/319 grant application cycle. Tremendous progress has been accomplished towards the original goals of the project. Due to the large number of Best Management Practices (BMPs) installed and the continued high interest for those practices, more work remains to be done. The heavy rains received in 2008 caused severe erosion and has dramatically increased interest in conservation practices. A thorough watershed assessment was completed in the fall of 2008. Data from this assessment indicates additional work is needed. The initial grant funding will be exhausted within fiscal year 2009. Therefore, the Howard Soil and Water Conservation District is seeking 3 years of funding. The District believes interest in the water quality project is at an all time high and that with an additional three years of funding, even more progress can be achieved in reducing sediment delivery and excess nutrients to these priority streams.