Trends in incidences and risk factors for hepatocellular carcinoma and other liver events in HIV and hepatitis C virus co-infected individuals from 2001 to 2014: a multi-cohort study.

BACKGROUND  While liver-related deaths in HIV and hepatitis C virus (HCV) co-infected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We described the epidemiology of HCC and other liver events in a multi-cohort collaboration of HIV/HCV co-infected individuals. METHODS  We studied all HCV antibody-positive adults with HIV in the EuroSIDA Study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort Study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios. RESULTS  Our study comprised 7,229 HIV/HCV co-infected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval (CI): 1.3, 2.0) and 8.6 (95% CI: 7.8, 9.5) cases per 1,000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI: 4%, 19%) and decreased 4% for other liver events (95% CI: 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. High age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events. CONCLUSIONS  In HIV/HCV co-infected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.

Les mécanismes sous-jacents aux effets pathologiques cardiaques de l’angiotensine II dans le remodelage électrique et contractile entre les sexes

L’insuffisance cardiaque (IC) est associée à un taux de mortalité et d’hospitalisations élevé causant un fardeau économique important. Les deux causes majeures de décès de l’IC sont les arythmies ventriculaires létales et les sidérations myocardiques. Il est maintenant reconnu que l’angiotensine II (ANGII) est l'un des principaux médiateurs de l’IC. Ses effets délétères découlent de l’activation du récepteur de type 1 de l’ANGII (AT1) et entraînent le développement d’hypertrophie. Toutefois, son rôle dans la genèse d’arythmies demeure incompris. De ce fait, l'étude des mécanismes électriques et contractiles sous-jacents aux effets pathologiques de l’ANGII s’avère essentielle afin de mieux comprendre et soigner cette pathologie. Il est souvent perçu que les femmes sont protégées envers les maladies cardiovasculaires. Cependant, le nombre total de femmes décédant d’IC est plus grand que le nombre d’hommes. Également, l’impact des facteurs de risque diffère entre chaque sexe. Ces différences existent, mais les mécanismes sous-jacents sont encore peu connus. De plus, les femmes reçoivent fréquemment un diagnostic ou un traitement inapproprié en raison d’un manque d’information sur les différences entre les sexes dans la manifestation d’une pathologie. Ce manque de données peut découler du fait que les sujets de sexe féminin sont souvent sous-représentés dans les essais cliniques ou la recherche fondamentale ce qui a grandement limité l’avancement de nos connaissances sur ~50 % de la population. Ainsi, il semble plus que nécessaire d’approfondir notre compréhension des différences entre les sexes, notamment dans la progression de l’IC. L’utilisation d’un modèle de souris transgénique surexprimant le récepteur AT1 (souris AT1R) a permis d’étudier les changements électriques, structurels et contractiles avant et après le développement d’hypertrophie. Premièrement, chez les souris AT1R mâles, un ralentissement de la conduction ventriculaire a été observé indépendamment de l’hypertrophie. Ce résultat était expliqué par une réduction de la densité du courant Na+, mais pas de l’expression du canal. Ensuite, le rôle des protéines kinases C (PKC) dans la régulation du canal Na+ par l’ANGII a été exploré. Les évidences ont suggéré que la PKCα était responsable de la modulation de la diminution du courant Na+ chez les souris AT1R mâles et dans les cardiomyocytes humains dérivés de cellules souches induites pluripotentes (hiPSC-CM) en réponse à un traitement chronique à l’ANGII. Ensuite, les différences entre les sexes ont été comparées chez la souris AT1R. Une plus grande mortalité a été constatée chez les femelles AT1R suggérant qu’elles sont plus sensibles à la surexpression de AT1R. Le remodelage électrique ventriculaire a donc été comparé entre les souris AT1R des deux sexes. Les courants ioniques étaient altérés de façon similaire entre les sexes excluant ainsi leur implication dans la mortalité plus élevée chez les femelles. Ensuite, l’homéostasie calcique et la fonction cardiaque ont été étudiées. Il a été démontré que les femelles développaient une hypertrophie et une dilatation ventriculaire plus sévère que les mâles. De plus, les femelles AT1R avaient de petits transitoires calciques, une extrusion du Ca2+ plus lente ainsi qu’une augmentation de la fréquence des étincelles Ca2+ pouvant participer à des troubles contractiles et à la venue de post-dépolarisations précoces. En conclusion, l’ANGII est impliquée dans le remodelage électrique, structurel et calcique associé à l'émergence de l’IC. De surcroît, ces altérations affectent plus sévèrement les femelles soulignant la présence de différences entre les sexes dans le développement de l’IC.

Legal shifts : shaping expectations of intellectual property protection in an open innovation industrial environment

Projet de recherche réalisé en 2014-2015 avec l'appui du Fonds de recherche du Québec – Société et culture.

Spatially explicit estimates of length and biomass of Micromesistius poutassou (Blue Whiting) from acoustic and trawl surveys in the North-East Atlantic in May 2012

Acoustic estimates of herring and blue whiting abundance were obtained during the surveys using the Simrad ER60 scientific echosounder. The allocation of NASC-values to herring, blue whiting and other acoustic targets were based on the composition of the trawl catches and the appearance of echo recordings. To estimate the abundance, the allocated NASC -values were averaged for ICES-squares (0.5° latitude by 1° longitude). For each statistical square, the unit area density of fish (rA) in number per square nautical mile (N*nm-2) was calculated using standard equations (Foote et al., 1987; Toresen et al., 1998). To estimate the total abundance of fish, the unit area abundance for each statistical square was multiplied by the number of square nautical miles in each statistical square and then summed for all the statistical squares within defined subareas and over the total area. Biomass estimation was calculated by multiplying abundance in numbers by the average weight of the fish in each statistical square then summing all squares within defined subareas and over the total area. The Norwegian BEAM soft-ware (Totland and Godø 2001) was used to make estimates of total biomass.

Greenland and Antarctic ice sheet topography, cavity geometry, and global bathymetry (RTopo-2), links to NetCDF files

The ocean plays an important role in modulating the mass balance of the polar ice sheets by interacting with the ice shelves in Antarctica and with the marine-terminating outlet glaciers in Greenland. Given that the flux of warm water onto the continental shelf and into the sub-ice cavities is steered by complex bathymetry, a detailed topography data set is an essential ingredient for models that address ice-ocean interaction. We followed the spirit of the global RTopo-1 data set and compiled consistent maps of global ocean bathymetry, upper and lower ice surface topographies and global surface height on a spherical grid with now 30-arc seconds resolution. We used the General Bathymetric Chart of the Oceans (GEBCO, 2014) as the backbone and added the International Bathymetric Chart of the Arctic Ocean version 3 (IBCAOv3) and the Interna- tional Bathymetric Chart of the Southern Ocean (IBCSO) version 1. While RTopo-1 primarily aimed at a good and consistent representation of the Antarctic ice sheet, ice shelves and sub-ice cavities, RTopo-2 now also contains ice topographies of the Greenland ice sheet and outlet glaciers. In particular, we aimed at a good representation of the fjord and shelf bathymetry sur- rounding the Greenland continent. We corrected data from earlier gridded products in the areas of Petermann Glacier, Hagen Bræ and Sermilik Fjord assuming that sub-ice and fjord bathymetries roughly follow plausible Last Glacial Maximum ice flow patterns. For the continental shelf off northeast Greenland and the floating ice tongue of Nioghalvfjerdsfjorden Glacier at about 79°N, we incorporated a high-resolution digital bathymetry model considering original multibeam survey data for the region. Radar data for surface topographies of the floating ice tongues of Nioghalvfjerdsfjorden Glacier and Zachariæ Isstrøm have been obtained from the data centers of Technical University of Denmark (DTU), Operation Icebridge (NASA/NSF) and Alfred Wegener Institute (AWI). For the Antarctic ice sheet/ice shelves, RTopo-2 largely relies on the Bedmap-2 product but applies corrections for the geometry of Getz, Abbot and Fimbul ice shelf cavities.

Massic magnetic susceptibility and CaCO3 content at the P. ohmi and T. hugii zones from the Rio Argos X.Ag-1 section, southeastern Spain

An orbital floating time scale of the Hauterivian-Barremian transition (Early Cretaceous) is proposed using high-resolution magnetic susceptibility measurements. Orbital tuning was performed on the Río Argos section (southeast Spain), the candidate for a Global boundary Stratotype Section and Point (GSSP) for the Hauterivian-Barremian transition. Spectral analyses of MS variations, coupled with the frequency ratio method, allow the recognition of precession, obliquity and eccentricity frequency bands. Orbitally-tuned magnetic susceptibility provides minimum durations for ammonite biozones. The durations of well-constrained ammonite zones are assessed at 0.78 myr for Pseudothurmannia ohmi (Late Hauterivian) and 0.57 myr for Taveraidiscus hugii (Early Barremian). These results are consistent with previous estimates from the other reference section (Angles, southeast France) and tend to show that the Río Argos section displays a complete succession for this time interval. They differ significantly from those proposed in the Geologic Time Scale 2008 and may help to improve the next compilation. The Faraoni Oceanic Anoxic Event, a key Early Cretaceous oceanographic perturbation occurring at the P. ohmi/P. catulloi subzone boundary has a duration estimated at 0.10-0.15 myr, which is similar to previous assessments.

Petrological and geochemical characteristics of DSDP Hole 37-334 gabbroic cumulates (Table 1)

The gabbronoritic cumulates drilled at DSDP Site 334 (Mid-Atlantic Ridge off the FAMOUS area) are neither crystallization products of the associated basalts, nor from any MORB composition documented along ocean ridges. Their parent melts are richer in SiO2 than MORB at a given MgO content, as attested by the crystallization sequence starting with an olivine+calcic and sub-calcic pyroxene assemblages. These melts are issued from a source highly depleted in incompatible elements, likely residual peridotite left after MORB extraction. To understand the role of water in the genesis of these lithologies whose occurrence in a mid-ocean ridge setting is rather puzzling, we performed a geochemical study on clinopyroxene separates following an analytical protocol able to remove the effects of water rock interactions post-dating their crystallization. Accordingly, the measured isotopic signatures can be used to trace magma sources. We find that Site 334 clinopyroxenes depart from the global mantle correlation: normal MORB values for the 143Nd/ 144Nd ratio (0.51307-0.51315) are associated to highly radiogenic 87Sr / 86Sr (0.7034-0.7067) ratios. This indicates that the parent melts of Site 334 cumulates are issued from a MORB source but that seawater contamination occurred at some stage of their genesis. The extent of contamination, traced by the Sr isotopic signature, is variable within all cumulates but more developed for gabbronorites sensus stricto, suggesting that seawater introduction was a continuous process during all the magmatic evolution of the system, from partial melting to fractional crystallization. Simple masse balance calculations are consistent with a contaminating agent having the characters of a highly hydrated (possibly water saturated) silica-rich melt depleted in almost all incompatible major, minor and trace elements relative to MORB. Mixing in various proportions of contaminated melts similar to the parent melts of Site 334 cumulates with MORB can account for part of the variability in the Sr isotopic signature of oceanic basalts, among other to the short wavelength isotopic "noise" superimposed on regional trends. We conclude that seawater introduction into residual peridotite at shallow depth beneath mid-ocean ridges can lead mantle rocks and their melts to follow complex P-T-fH2O paths that mimic petrogenetic contexts classically attributed to subduction zone environments, like the production of boninitic-andesitic magmas.

Micromesistius poutassou (blue whiting) abundance and biomass data in Bay of Biscay estimated from acoustic surveys (2000-2012)

Acoustic and pelagic trawl data were collected during various pelagic surveys carried out by IFREMER in May between 2000 and 2012 (except 2001), on the eastern continental shelf of the Bay of Biscay (Pelgas series). The acoustic data were collected with a Simrad EK60 echosounder operating at 38 kHz (beam angle at -3 dB: 7°, pulse length set to 1.024 ms). The echosounder transducer was mounted on the vessel keel, at 6 m below the sea surface. The sampling design were parallel transects spaced 12 nm apart which were orientated perpendicular to the coast line from 20 m to about 200 m bottom depth. The nominal sailing speed was 10 knots and 3 knots on average during fishing operations. The scrutinising (species identification) of acoustic data was done by first characterising acoustic schools by type and then linking these types with the species composition of specific trawl hauls. The data set contains nautical area backscattering values, biomass and abundance estimates for blue whiting for one nautical mile long transect lines. Further information on the survey design, scrutinising and biomass estimation can be found in Doray et al. 2012.

Survey bottom trawl data of Micromesistius poutassou (blue whiting) in Bay of Biscay and Celtic Sea from the EVHOE time series (1997-2011)

Data were collected during various groundfish surveys carried out by IFREMER from October to December between 1997 and 2011, on the eastern continental shelf of the Bay of Biscay and in the Celtic Sea (EVHOE series). The sampling design was stratified according to latitude and depth. A 36/47 GOV trawl was used with a 20 mm mesh codend liner. Haul duration was 30 minutes at a towing speed of 4 knots. Fishing was restricted to daylight hours. Catch weights and catch numbers were recorded for all species and body size measured. The weights and numbers per haul were transformed into abundances per km**2 by considering the swept area of a standard haul (0.069 km**2).

Complete method of vocalization for the mezzo-soprano.

Mode of access: Internet.

Catalogue of a collection of pictures, including examples of the works of the brothers Le Nain, and other works of art.

"Suggested classification of the works of the brothers Le Nain," signed R. C. W. [i.e. Robert C. Witt]: p. 7-20.

Mission du Général Gardane en Perse sous le premier empire; documents historiques.

Mode of access: Internet.

Le comte Molé, 1781-1855 : sa vie--ses mémoires.

At head of title: Marquis de Noailles.

Lettres de l'abbé Lebeuf publiées par la Société des sciences historiques et naturelles de l'Yonne,

Mode of access: Internet.