Use of Oral Cholera Vaccine in Haiti: A Rural Demonstration Project

A cholera epidemic has claimed the lives of more than 8,000 Haitians and sickened 650,000 since the outbreak began in October 2010. Early intervention in the epidemic focused on case-finding, treatment, and water and sanitation interventions for prevention of transmission. Use of oral cholera vaccine (OCV) as part of a complementary set of control activities was considered but initially rejected by policymakers. In December 2011, the Minister of Health of Haiti called for a demonstration of the acceptability and feasibility of the use of OCV in urban and rural Haiti. This paper describes the collaborative activity that offered OCV to one region of the Artibonite Department of rural Haiti in addition to other ongoing treatment and control measures. Despite logistics and cold chain challenges, 45,417 persons were successfully vaccinated with OCV in the region, and 90.8% of these persons completed their second dose

On the Benefits of Transparent Compression for Cost-Effective Cloud Data Storage

International audienceInfrastructure-as-a-Service (IaaS) cloud computing has revolutionized the way we think of acquiring computational resources: it allows users to deploy virtual machines (VMs) at large scale and pay only for the resources that were actually used throughout the runtime of the VMs. This new model raises new challenges in the design and development of IaaS middleware: excessive storage costs associated with both user data and VM images might make the cloud less attractive, especially for users that need to manipulate huge data sets and a large number of VM images. Storage costs result not only from storage space utilization, but also from bandwidth consumption: in typical deployments, a large number of data transfers between the VMs and the persistent storage are performed, all under high performance requirements. This paper evaluates the trade-off resulting from transparently applying data compression to conserve storage space and bandwidth at the cost of slight computational overhead. We aim at reducing the storage space and bandwidth needs with minimal impact on data access performance. Our solution builds on BlobSeer, a distributed data management service specifically designed to sustain a high throughput for concurrent accesses to huge data sequences that are distributed at large scale. Extensive experiments demonstrate that our approach achieves large reductions (at least 40%) of bandwidth and storage space utilization, while still attaining high performance levels that even surpass the original (no compression) performance levels in several data-intensive scenarios

Hepatocellular adenoma: what is new in 2008

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1α (HNF1α) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1α-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1α germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating β-catenin mutation was found in 10% of HCA. These β-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress β-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express β-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1α-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Overview of the Chemistry-Aerosol Mediterranean Experiment/Aerosol Direct Radiative Forcing on the Mediterranean Climate (ChArMEx/ADRIMED) summer 2013 campaign

The Chemistry-Aerosol Mediterranean Experiment (ChArMEx; http://charmex.lsce.ipsl.fr) is a collaborative research program federating international activities to investigate Mediterranean regional chemistry-climate interactions. A special observing period (SOP-1a) including intensive airborne measurements was performed in the framework of the Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region (ADRIMED) project during the Mediterranean dry season over the western and central Mediterranean basins, with a focus on aerosol-radiation measurements and their modeling. The SOP-1a took place from 11 June to 5 July 2013. Airborne measurements were made by both the ATR-42 and F-20 French research aircraft operated from Sardinia (Italy) and instrumented for in situ and remote-sensing measurements, respectively, and by sounding and drifting balloons, launched in Minorca. The experimental setup also involved several ground-based measurement sites on islands including two ground-based reference stations in Corsica and Lampedusa and secondary monitoring sites in Minorca and Sicily. Additional measurements including lidar profiling were also performed on alert during aircraft operations at EARLINET/ACTRIS stations at Granada and Barcelona in Spain, and in southern Italy. Remote-sensing aerosol products from satellites (MSG/SEVIRI, MODIS) and from the AERONET/PHOTONS network were also used. Dedicated meso-scale and regional modeling experiments were performed in relation to this observational effort. We provide here an overview of the different surface and aircraft observations deployed during the ChArMEx/ADRIMED period and of associated modeling studies together with an analysis of the synoptic conditions that determined the aerosol emission and transport. Meteorological conditions observed during this campaign (moderate temperatures and southern flows) were not favorable to producing high levels of atmospheric pollutants or intense biomass burning events in the region. However, numerous mineral dust plumes were observed during the campaign, with the main sources located in Morocco, Algeria and Tunisia, leading to aerosol optical depth (AOD) values ranging between 0.2 and 0.6 (at 440 nm) over the western and central Mediterranean basins. One important point of this experiment concerns the direct observations of aerosol extinction onboard the ATR-42, using the CAPS system, showing local maxima reaching up to 150Mm(-1) within the dust plume. Non-negligible aerosol extinction (about 50Mm(-1)) has also been observed within the marine boundary layer (MBL). By combining the ATR- 42 extinction coefficient observations with absorption and scattering measurements, we performed a complete optical closure revealing excellent agreement with estimated optical properties. This additional information on extinction properties has allowed calculation of the dust single scattering albedo (SSA) with a high level of confidence over the western Mediterranean. Our results show a moderate variability from 0.90 to 1.00 (at 530 nm) for all flights studied compared to that reported in the literature on this optical parameter. Our results underline also a relatively low difference in SSA with values derived near dust sources. In parallel, active remote-sensing observations from the surface and onboard the F-20 aircraft suggest a complex vertical structure of particles and distinct aerosol layers with sea spray and pollution located within the MBL, and mineral dust and/or aged North American smoke particles located above (up to 6–7 km in altitude). Aircraft and balloon-borne observations allow one to investigate the vertical structure of the aerosol size distribution showing particles characterized by a large size (> 10 μm in diameter) within dust plumes. In most of cases, a coarse mode characterized by an effective diameter ranging between 5 and 10 μm, has been detected above the MBL. In terms of shortwave (SW) direct forcing, in situ surface and aircraft observations have been merged and used as inputs in 1-D radiative transfer codes for calculating the aerosol direct radiative forcing (DRF). Results show significant surface SW instantaneous forcing (up to (-90)Wm(-2) at noon). Aircraft observations provide also original estimates of the vertical structure of SW and LW radiative heating revealing significant instantaneous values of about 5 K per day in the solar spectrum (for a solar angle of 30 ) within the dust layer. Associated 3-D modeling studies from regional climate (RCM) and chemistry transport (CTM) models indicate a relatively good agreement for simulated AOD compared with observations from the AERONET/PHOTONS network and satellite data, especially for long-range dust transport. Calculations of the 3-D SW (clear-sky) surface DRF indicate an average of about -10 to -20Wm(-2) (for the whole period) over the Mediterranean Sea together with maxima (-50Wm(-2)) over northern Africa. The top of the atmosphere (TOA) DRF is shown to be highly variable within the domain, due to moderate absorbing properties of dust and changes in the surface albedo. Indeed, 3-D simulations indicate negative forcing over the Mediterranean Sea and Europe and positive forcing over northern Africa. Finally, a multiyear simulation, performed for the 2003 to 2009 period and including an ocean–atmosphere (O–A) coupling, underlines the impact of the aerosol direct radiative forcing on the sea surface temperature, O–A fluxes and the hydrological cycle over the Mediterranean.French National Research Agency (ANR) ANR-11-BS56-0006ADEMEFrench Atomic Energy CommissionCNRS-INSU and Meteo-France through the multidisciplinary programme MISTRALS (Mediterranean Integrated Studies aT Regional And Local Scales)CORSiCA project - Collectivite Territoriale de Corse through Fonds Europeen de Developpement Regional of the European Operational ProgramContrat de Plan Etat-RegionEuropean Union's Horizon 2020 research and innovation program 654169Spanish Ministry of Economy and Competitivity TEC2012-34575Science and Innovation UNPC10-4E-442European Union (EU)Department of Economy and Knowledge of the Catalan Autonomous Government SGR 583Andalusian Regional Government P12-RNM-2409Spanish Government CGL2013-45410-R 26225

Spectrum of HNF1A Somatic Mutations in Hepatocellular Adenoma Differs From That in Patients With MODY3 and Suggests Genotoxic Damage

OBJECTIVE Maturity onset diabetes of the young type 3 (MODY3) is a consequence of heterozygous germline mutation in HNF1A. A subtype of hepatocellular adenoma (HCA) is also caused by biallelic somatic HNF1A mutations (H-HCA), and rare HCA may be related to MODY3. To better understand a relationship between the development of MODY3 and HCA, we compared both germline and somatic spectra of HNF1A mutations. RESEARCH DESIGN AND METHODS We compared 151 somatic HNF1A mutations in HCA with 364 germline mutations described in MODY3. We searched for genotoxic and oxidative stress features in HCA and surrounding liver tissue. RESULTS A spectrum of HNF1A somatic mutations significantly differed from the germline changes in MODY3. In HCA, we identified a specific hot spot at codon 206, nonsense and frameshift mutations mainly in the NH2-terminal part, and almost all amino acid substitutions were restricted to the POU-H domain. The high frequency of G-to-T tranversions, predominantly found on the nontranscribed DNA strand, suggested a genotoxic mechanism. However, no features of oxidative stress were observed in the nontumor liver tissue. Finally, in a few MODY3 patients with HNF1A germline mutation leading to amino acid substitutions outside the POU-H domain, we identified a different subtype of HCA either with a gp130 and/or CTNNB1 activating mutation. CONCLUSIONS Germline HNF1A mutations could be associated with different molecular subtypes of HCA. H-HCA showed mutations profoundly inactivating hepatocyte nuclear factor-1α function; they are associated with a genotoxic signature suggesting a specific toxicant exposure that could be associated with genetic predisposition

Author Correction: Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial (Nature Medicine, (2021), 27, 11, (2012-2024), 10.1038/s41591-021-01488-2)

In the version of this Article initially published, there was an omission in the member list for the CONCOR-1 Study Group. Valérie Arsenault (Héma-Québec, Montreal, Quebec, Canada) has now been included in the CONCOR-1 Study Group in the online version of the article