A new stepwise carbon cycle data assimilation system using multiple data streams to constrain the simulated land surface carbon cycle

Acknowledgements. This work was mainly funded by the EU FP7 CARBONES project (contracts FP7-SPACE-2009-1-242316), with also a small contribution from GEOCARBON project (ENV.2011.4.1.1-1-283080). This work used eddy covariance data acquired by the FLUXNET community and in particular by the following networks: AmeriFlux (U.S. Department of Energy, Biological and Environmental Research, Terrestrial Carbon Program; DE-FG02-04ER63917 and DE-FG02-04ER63911), AfriFlux, AsiaFlux, CarboAfrica, CarboEuropeIP, CarboItaly, CarboMont, ChinaFlux, Fluxnet-Canada (supported by CFCAS, NSERC, BIOCAP, Environment Canada, and NRCan), GreenGrass, KoFlux, LBA, NECC, OzFlux, TCOS-Siberia, USCCC. We acknowledge the financial support to the eddy covariance data harmonization provided by CarboEuropeIP, FAO-GTOS-TCO, iLEAPS, Max Planck Institute for Biogeochemistry, National Science Foundation, University of Tuscia, Université Laval and Environment Canada and US Department of Energy and the database development and technical support from Berkeley Water Center, Lawrence Berkeley National Laboratory, Microsoft Research eScience, Oak Ridge National Laboratory, University of California-Berkeley, University of Virginia. Philippe Ciais acknowledges support from the European Research Council through Synergy grant ERC-2013-SyG-610028 “IMBALANCE-P”. The authors wish to thank M. Jung for providing access to the GPP MTE data, which were downloaded from the GEOCARBON data portal (https://www.bgc-jena.mpg.de/geodb/projects/Data.php). The authors are also grateful to computing support and resources provided at LSCE and to the overall ORCHIDEE project that coordinate the development of the code (http://labex.ipsl.fr/orchidee/index.php/about-the-team).Peer reviewedPublisher PD

Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age. METHODS AND FINDINGS: SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68-1.2, p = 0.496). A reduction of 60% (95% CI 54%-64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%-72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%-33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%-35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%-68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%-85%) p = 0.002 in 2008, 84% (95% CI 58%-94%, p < 0.001) in 2009, and 30% (95% CI -130%-79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. CONCLUSIONS: SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712374

Author Correction: Implementation, coverage and equity of large-scale door-to-door delivery of Seasonal Malaria Chemoprevention (SMC) to children under 10 in Senegal.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

Zebrafish ProVEGF-C Expression, Proteolytic Processing and Inhibitory Effect of Unprocessed ProVEGF-C during Fin Regeneration

BACKGROUND: In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR(214) suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. In the present study, we examined zebrafish proVEGF-C expression and processing and the effect of unprocessed proVEGF-C on caudal fin regeneration. METHODOLOGY/PRINCIPAL FINDINGS: Cell transfection assays revealed that the cleavage of proVEGF-C, mainly mediated by the proprotein convertases Furin and PC5 and to a less degree by PACE4 and PC7, is abolished by PCs inhibitors or by mutation of its cleavage site (HSIIRR(214) into HSIISS(214)). In vitro, unprocessed proVEGF-C failed to activate its signaling proteins Akt and ERK and to induce cell proliferation. In vivo, following caudal fin amputation, the induction of VEGF-C, Furin and PC5 expression occurs as early as 2 days post-amputation (dpa) with a maximum levels at 4-7 dpa. Using immunofluorescence staining we localized high expression of VEGF-C and the convertases Furin and PC5 surrounding the apical growth zone of the regenerating fin. While expression of wild-type proVEGF-C in this area had no effect, unprocessed proVEGF-C inhibited fin regeneration. CONCLUSIONS/SIGNIFICANCES: Taken together, these data indicate that zebrafish fin regeneration is associated with up-regulation of VEGF-C and the convertases Furin and PC5 and highlight the inhibitory effect of unprocessed proVEGF-C on fin regeneration

Impact of chronic obstructive pulmonary disease and dyspnoea on clinical outcomes in ticagrelor treated patients undergoing percutaneous coronary intervention in the randomized GLOBAL LEADERS trial

AIMS: To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence. METHODS AND RESULTS: This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-mo

Standards for Libraries in Higher Education

The Standards for Libraries in Higher Education are designed to guide academic libraries in advancing and sustaining their role as partners in educating students, achieving their institutions’ missions, and positioning libraries as leaders in assessment and continuous improvement on their campuses. Libraries must demonstrate their value and document their contributions to overall institutional effectiveness and be prepared to address changes in higher education. These Standards were developed through study and consideration of new and emerging issues and trends in libraries, higher education, and accrediting practices. These Standards differ from previous versions by articulating expectations for library contributions to institutional effectiveness. These Standards differ structurally by providing a comprehensive framework using an outcomes-based approach, with evidence collected in ways most appropriate for each institution

Observation and Theory in Science

Originally published in 1971. The three contributions collected in this volume deal with different aspects of a single theme—the logical status of scientific theories in their relation to observation. These lectures, authored by different thinkers, treat this theme in connection with some controversies in the philosophy of science. A nonspecialist who reads these lectures should realize that the theme itself is a perennial one with an ancient lineage. It has concerned philosophers from the earliest era of philosophy on down through the centuries. A central philosophical issue at stake in the lectures is the question of whether scientific theories are testable in terms of our observations such that we can know whether some theories are true and others false. Although differing in their emphases, all three contributors seek a more plausible and nonskeptical philosophical account of the status of scientific theories in relation to observation

La relation entre l'ouverture commerciale et l'industrialisation en Afrique centrale

Since independence in the 1960s, Central African countries have recorded poor performance in the manufacturing industry. Several industrial strategies were experimented with, in particular import substitution in the 1960s and 1970s, and macroeconomic stabilization reforms in the 1980s and 1990s to improve the international competitiveness of Central African firms.With the application of the reforms, the countries of Central Africa have chosen trade openness. Thus, the objectives of this research were to understand and explain the effects of trade openness on industrialization in Central Africa. Because, industrialization has a preponderant role in the economic development of nations. Very few countries have reached the stage of developed countries without an efficient industrial base. The low level of development of the manufacturing industry in Central Africa does not offer enough job opportunities to the working population, which is growing in number, resulting in an increase in its level of poverty.The research concerned the 11 members countries of the Economic Community of Central African States (ECCAS). To conduct this research, we used the basic theoretical model of Lucas (1988), in order to highlight the empirical link between trade openness and the performance of the manufacturing industry. We used panel data regressions with the fixed effects estimation method.At the end of the research, we found a positive effect of trade openness on the performance of the manufacturing industry. Indeed, the 1% increase in trade as a percentage of GDP leads to a 2.3% increase in the value added of manufacturing industry as a percentage of GDP. Similarly, the impact of an additional year of schooling results in an 8% increase in the added value of manufacturing industry as a percentage of GDP. Finally, increasing the proportion of the active population in the population by 1% makes it possible to improve the added value of the manufacturing industry by around 58% as a percentage of GDP. However, this last result highlights the low technological intensity of processing activities in Central African countries, which require more unskilled labor.In view of these results, trade openness alone is not enough for industrial growth, it is necessary to complement this process with investments in the development of skills and knowledge. Consequently, industrialization should be conducted according to a comprehensive approach combining both trade strategies and those of developing the productive capacities of Central Africa. The completion of the economic integration process in the Economic Community of Central African States should help consolidate the industrialization process.Depuis les indépendances dans les années 1960, les pays de l’Afrique centrale ont enregistré des faibles performances dans l’industrie manufacturière. Plusieurs stratégies industrielles ont été expérimentées, en particulier la substitution aux importations dans les années 1960 et 1970, et les réformes de stabilisation macroéconomiques dans les années 1980 et 1990 pour améliorer la compétitivité internationale des entreprises de l’Afrique centrale. Avec l’application des réformes, les pays de l’Afrique centrale ont choisi l’ouverture commerciale. Ainsi, les objectifs de cette recherche ont été de comprendre et d’expliquer les effets de l’ouverture commerciale sur l’industrialisation en Afrique centrale. Car, l’industrialisation a un rôle prépondérant dans le développement économique des nations. Très peu de pays sont parvenus au stade des pays développés sans une base industrielle performante. Le faible niveau de développement de l’industrie manufacturière en Afrique centrale ne propose pas suffisamment d’opportunités d’emplois à la population active, de plus en plus nombreuse, avec pour conséquences l’augmentation du niveau de pauvreté de celle-ci.La recherche a concerné les 11 pays membres de la Communauté Economique des Etats de l’Afrique Centrale (CEEAC). Pour mener cette recherche, nous avons eu recours au modèle théorique de base de Lucas (1988), afin de mettre en évidence le lien empirique entre l’ouverture commerciale et la performance de l’industrie manufacturière. Nous avons utilisé des régressions en données de panel avec la méthode d’estimation à effets fixes.Au terme de la recherche, nous avons constaté un effet positif de l’ouverture commerciale sur la performance de l’industrie manufacturière. En effet, l’augmentation de 1% du commerce en pourcentage du PIB entraîne l’augmentation de 2,3% de la valeur ajoutée de l’industrie manufacturière en pourcentage du PIB. De même, l’incidence d’une année supplémentaire d’études scolaires permet d’obtenir un accroissement de 8% de la valeur ajoutée de l’industrie manufacturière en pourcentage du PIB. Enfin, l’augmentation de la proportion de la population active dans la population de 1% permet d’améliorer d’environ 58% la valeur ajoutée de l’industrie manufacturière en pourcentage du PIB. Toutefois, ce dernier résultat met en lumière la faible intensité technologique des activités de transformation dans les pays de l’Afrique centrale, qui requièrent davantage une main-d’œuvre peu qualifiée.Au regard de ces résultats, l’ouverture commerciale à elle seule ne suffit pas à soutenir la croissance industrielle, il est nécessaire de compléter ce processus par des investissements dans le développement des compétences et le savoir. Par conséquent, l’industrialisation devrait être conduit selon une approche globale combinant à la fois les stratégies commerciales et celles de développement des capacités productives de l’Afrique centrale. L’achèvement du processus d’intégration économique dans la communauté économique des Etats de l’Afrique centrale devrait permettre de consolider le processus d’industrialisation

Prevalence of chronic kidney disease in Kinshasa: results of a pilot study from the Democratic Republic of Congo

Abstract Background. The burden of chronic kidney disease (CKD) in sub-Saharan Africa is unknown. The aim of this study was to investigate the prevalence and the risk factors associated with CKD in Kinshasa, the capital of the Democratic Republic of Congo (DRC). Methods. In a cross-sectional study, 503 adult residents in 10 of the 35 health zones of Kinshasa were studied in a randomly selected sample. Glomerular filtration rate was estimated using the simplified Modification of Diet in Renal Disease Study equation (eGFR) and compared with the Cockcroft–Gault equation for creatinine clearance. The associations between health characteristics, indicators of kidney damage (proteinuria) and kidney function (<60 ml/min/1.73 m2) were examined. Results. The prevalence of all stages of CKD according to K/DOQI guidelines was 12.4% [95% confidence interval (CI), 11.0–15.1%]. By stage, 2% had stage 1 (proteinuria with normal eGFR), 2.4% had stage 2 (proteinuria with an eGFR of 60–89 ml/min/1.73 m2), 7.8% had stage 3 (eGFR, 30–59 ml/min/1.73 m2) and 0.2% had stage 5 (eGFR < 15 ml/min/1.73 m2). Hypertension and age were independently associated with CKD stage 3. The prevalences of major non-communicable diseases considered in this study were 27.6% (95% CI, 25.7–31.3%) for hypertension, 11.7% (95% CI, 10.3–14.4%) for diabetes mellitus and 14.9% (95% CI, 13.3–17.9%) for obesity. Hypertension was also independently associated with proteinuria. Conclusion. More than 10% of the Kinshasa population exhibits signs of CKD, which is affecting adults in their productive years. Risk factors for CKD, including hypertension, diabetes and obesity, are increasing. These alarming data must guide current and future healthcare policies to meet the challenge raised by CKD in this city and hopefully in the whole country

Essential requirement for zebrafish anosmin-1a in the migration of the posterior lateral line primordium.

International audienceKallmann syndrome (KS) is a human genetic disease that impairs both cell migration and axon elongation. The KAL-1 gene underlying the X-linked form of KS, encodes an extracellular matrix protein, anosmin-1, which mediates cell adhesion and axon growth and guidance in vitro. We investigated the requirement for kal1a and kal1b, the two orthologues of the KAL-1 gene in zebrafish, in the journey of the posterior lateral line primordium (PLLP). First, we established that while the accumulation of kal1a and kal1b transcripts was restricted to the posterior region of the migrating primordium and newly deposited neuromasts, the encoded proteins, anosmin-1a and anosmin-1b, respectively, were accumulated in the PLLP, in differentiated neuromasts and in a thin strip extending along the trail path of the PLLP. We also show that morpholino knockdown of kal1a, but not kal1b, severely impairs PLLP migration. However, while the PLLP of kal1a morphants displays highly abnormal morphology, proper expression of the cxcr4b gene suggests that kal1a does not play a role in PLLP differentiation. Conversely, wild-type levels of kal1a transcripts are detected in the PLLP of cxcr4b or sdf1a morphant embryos, strongly suggesting that kal1a transcription is independent of CXCR4b/SDF1a signalling. Last, moderate depletion of both anosmin-1a and SDF1a markedly affects PLLP migration providing strong evidence that anosmin-1a acts as an essential co-factor in SDF1a-mediated signalling pathways. Our findings, which demonstrate, for the first time, an essential requirement for anosmin-1a in PLLP migration, also strongly suggest that this protein plays a key role for proper activation of the CXCR4b/SDF1a and/or CXCR7/SDF1a signalling pathway in PLLP migration