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The following research paper conducts a comprehensive analysis into the intricate dynamics governing the relationship between Foreign Direct Investment (FDI) and International Trade, with a specific focus on the Western Balkan Countries-6 (WB-6). This research spans the period from 2000 to 2020 and seeks to shed light on the interplay between FDI and International Trade within this region. To analyse and interpret these dynamics, various regression models, including Ordinary Least Squares (OLS), Fixed Effects, Random Effects, and the Hausman-Taylor model, are employed as analytical tools. Moreover, the research takes into consideration the influence of specific institutional factors within each country, which play a pivotal role in shaping foreign investors' decisions to invest in a particular country. The study's results reveal that gravity factors, in conjunction with institutional determinants such as economic integration, control of corruption, political stability, and other indicators of governance quality, significantly impact the attractiveness of the WB-6 countries to foreign investors. The findings of this paper hold substantial relevance for the development of an analytical framework aimed at evaluating national policies and institutions geared towards enhancing the appeal of Western Balkan countries to foreign investors. Furthermore, the research underscores the importance of these host countries prioritizing efforts to bolster the effectiveness of governmental institutions, combat corruption, streamline bureaucratic processes, and improve overall economic conditions to attract and retain foreign investment. [ABSTRACT FROM AUTHOR]

A major endeavor of this decade is the direct characterization of young giant exoplanets at high spectral resolution to determine the composition of their atmosphere and infer their formation processes and evolution. Such a goal represents a major challenge owing to their small angular separation and luminosity contrast with respect to their parent stars. Instead of designing and implementing completely new facilities, it has been proposed to leverage the capabilities of existing instruments that offer either high-contrast imaging or high-dispersion spectroscopy by coupling them using optical fibers. In this work, we present the implementation and first on-sky results of the High-Resolution Imaging and Spectroscopy of Exoplanets (HiRISE) instrument at the Very Large Telescope (VLT), which combines the exoplanet imager SPHERE with the recently upgraded high-resolution spectrograph CRIRES using single-mode fibers. The goal of HiRISE is to enable the characterization of known companions in the H band at a spectral resolution on the order of R = λ/∆λ = 100 000 in a few hours of observing time. We present the main design choices and the technical implementation of the system, which is constituted of three major parts: the fiber injection module inside of SPHERE, the fiber bundle around the telescope, and the fiber extraction module at the entrance of CRIRES. We also detail the specific calibrations required for HiRISE and the operations of the instrument for science observations. Finally, we detail the performance of the system in terms of astrometry, temporal stability, optical aberrations, and transmission, for which we report a peak value of ~3.9% based on sky measurements in median observing conditions. Finally, we report on the first astrophysical detection of HiRISE to illustrate its potential. [ABSTRACT FROM AUTHOR]

Polar and subpolar oceans play a particularly important role in the global climate and its temporal changes, yet these regions are less well sampled than the rest of the global ocean. To better understand the physical or biogeochemical properties and their variabilities in these regions, accurate data mapping is crucial. In this paper, we introduce a mapping methodology that includes a water column shrinking and stretching constraint (SSC) based on the principle of conservation of potential vorticity. To demonstrate the mapping scheme efficiency, we map the ocean temperature in the southern Sea of Okhotsk, where the bottom topography comprises a broad and shallow shelf, a sharp continental slope, and a deep oceanic basin. Such topographic features are typical of polar and subpolar marginal seas. Results reveal that the SSC integrated (SSCI) mapping strongly reduces the mapping error in the broad and shallow shelf compared with a recently introduced topographic constraint integrated (TCI) mapping procedure. We also tested our mapping scheme in the Southern Ocean, which has a comparatively slanted shelf, a wider and gentler slope, and a deep and broad oceanic basin. We found that the SSCI and TCI methods are practically equivalent there. The SSCI mapping is thus an effective method to map the ocean's properties in various topographic environments and should be adequate in all polar and subpolar regions. Importantly, we introduced a standardized procedure for determining the decorrelation length scales—a necessary step prior to implementing any mapping scheme—in any topographic conditions. [ABSTRACT FROM AUTHOR]

• A 70-year record of sea ice meltwater thickness was created from ocean data. • A decline in the Bering Sea ice production and meltwater volume occurred after 1980. • The salinity of the sea ice production-related PWW has decreased by 0.3 in 70 years. • The above-mentioned changes have weakened the stratification in the coastal regions. • The stratification is increasingly controlled by temperature away from the coast. Large amounts of freshwater and nutrients pass through the Bering Strait to the Arctic Ocean, making the Bering Sea a crucial marginal sea of the North Pacific Ocean. The hydrography and biological production of the Bering Sea are strongly influenced by the amount of sea ice produced and melted. The sea ice extent and production exhibited large interannual variability but no visible trend until 2016 when a strong decrease began. However, records of sea ice before 1979 and the beginning of satellite-based estimates do not exist. In this paper, we devised a methodology using historical temperature and salinity data, supplemented by historical oxygen isotope (δ18O) data, to estimate sea ice melt and its temporal variability in the Bering Sea from 1950 onward. Our results, consistent with estimates of sea ice thickness, indicate that the sea ice melt volume has declined significantly —following lower sea ice extent and production— with a decrease between 35 and 50 km3 (from 442 km3) between pre-1980 and post-1980 climatologies. In particular, our meltwater time series reveals a decline of 160 km3 between 2012 and 2018, which also reflects the strong decrease in sea ice volume between 2016 and 2018 that numerous previous studies have highlighted. We also evaluated the change in the salinity of the Pacific Winter Water (PWW), whose formation is also related to sea ice production. The time series of PWW salinity exhibits a strong decreasing trend, with a freshening of about 0.3 between the mid-1950s and the mid-2010s, that we attribute to a combination of a reduced sea ice production and the freshening of the Alaskan Coastal Current water. The decline in meltwater volume and PWW salinity that we observed strongly influences the stratification over the Bering shelf, with a significant weakening of the stratification in coastal polynya regions, and a stronger and increasingly temperature-controlled stratification in the rest of the shelf. These changes could have adverse consequences on the biological productivity of the northern Bering Sea. [ABSTRACT FROM AUTHOR]

Profiling of the antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in African populations is scarce. Here, we performed a detailed IgM and IgG epitope mapping study against 487 peptides covering SARS-CoV-2 wild-type structural proteins. A panel of 41 pre-pandemic and 82 COVID-19 RT-PCR confirmed sera from Madagascar and Senegal were used. We found that the main 36 immunodominant linear epitopes identified were (i) similar in both countries, (ii) distributed mainly in the Spike and the Nucleocapsid proteins, (iii) located outside the RBD and NTD regions where most of the reported SARS-CoV-2 variant mutations occur, and (iv) identical to those reported in European, North American, and Asian studies. Within the severe group, antibody levels were inversely correlated with the viral load. This first antibody epitope mapping study performed in patients from two African countries may be helpful to guide rational peptide-based diagnostic assays or vaccine development. [ABSTRACT FROM AUTHOR]

Background: Targeted research on residual malaria transmission is important to improve strategies in settings pursuing elimination, where transmission reductions prove challenging. This study aimed to detect and characterize spatial heterogeneity and factors associated with Plasmodium falciparum infections and exposure, P. falciparum apical membrane antigen 1 (PfAMA1) antibody (Ab) response, in the Central Highlands of Madagascar (CHL). Methods: From May to July 2014, a cross-sectional school-based survey was carried out in 182 fokontany (villages) within 7 health districts of the CHL. Rapid diagnostic tests (RDTs) and a bead-based immunoassay including PfAMA1 antigen biomarker were used to estimate malaria prevalence and seroprevalence, respectively. Local Moran's I index was used to detect spatial "hotspots". Remotely sensed environmental data—temperature, vegetation indices, land covers, and elevation—were used in multivariable mixed-effects logistic regression models to characterize factors associated with malaria infection and cumulative exposure. Results: Among 6,293 school-children ages 2–14 years surveyed, RDT prevalence was low at 0.8% (95% CI 0.6–1.1%), while PfAMA1 Ab seroprevalence was 7.0% (95% CI 6.4–7.7%). Hotspots of PfAMA1 Ab seroprevalence were observed in two districts (Ankazobe and Mandoto). Seroprevalence increased for children living > 5 km from a health centre (adjusted odds ratio (OR) = 1.6, 95% CI 1.2–2.2), and for those experiencing a fever episode in the previous 2 weeks (OR 1.7, 95% CI 1.2–2.4), but decreased at higher elevation (for each 100-m increase, OR = 0.7, 95% CI 0.6–0.8). A clear age pattern was observed whereby children 9–10 years old had an OR of 1.8 (95% CI 1.2–2.4), children 11–12 years an OR of 3.7 (95% CI 2.8–5.0), and children 13–14 years an OR of 5.7 (95% CI 4.0–8.0) for seropositivity, compared with younger children (2–8 years). Conclusion: The use of serology in this study provided a better understanding of malaria hotspots and associated factors, revealing a pattern of higher transmission linked to geographical barriers in health care access. The integration of antibody-assays into existing surveillance activities could improve exposure assessment, and may help to monitor the effectiveness of malaria control efforts and adapt elimination interventions. [ABSTRACT FROM AUTHOR]

Background: Targeted research on residual malaria transmission is important to improve strategies in settings pursuing elimination, where transmission reductions prove challenging. This study aimed to detect and characterize spatial heterogeneity and factors associated with Plasmodium falciparum infections and exposure, P. falciparum apical membrane antigen 1 (PfAMA1) antibody (Ab) response, in the Central Highlands of Madagascar (CHL). Methods: From May to July 2014, a cross-sectional school-based survey was carried out in 182 fokontany (villages) within 7 health districts of the CHL. Rapid diagnostic tests (RDTs) and a bead-based immunoassay including PfAMA1 antigen biomarker were used to estimate malaria prevalence and seroprevalence, respectively. Local Moran's I index was used to detect spatial "hotspots". Remotely sensed environmental data—temperature, vegetation indices, land covers, and elevation—were used in multivariable mixed-effects logistic regression models to characterize factors associated with malaria infection and cumulative exposure. Results: Among 6,293 school-children ages 2–14 years surveyed, RDT prevalence was low at 0.8% (95% CI 0.6–1.1%), while PfAMA1 Ab seroprevalence was 7.0% (95% CI 6.4–7.7%). Hotspots of PfAMA1 Ab seroprevalence were observed in two districts (Ankazobe and Mandoto). Seroprevalence increased for children living > 5 km from a health centre (adjusted odds ratio (OR) = 1.6, 95% CI 1.2–2.2), and for those experiencing a fever episode in the previous 2 weeks (OR 1.7, 95% CI 1.2–2.4), but decreased at higher elevation (for each 100-m increase, OR = 0.7, 95% CI 0.6–0.8). A clear age pattern was observed whereby children 9–10 years old had an OR of 1.8 (95% CI 1.2–2.4), children 11–12 years an OR of 3.7 (95% CI 2.8–5.0), and children 13–14 years an OR of 5.7 (95% CI 4.0–8.0) for seropositivity, compared with younger children (2–8 years). Conclusion: The use of serology in this study provided a better understanding of malaria hotspots and associated factors, revealing a pattern of higher transmission linked to geographical barriers in health care access. The integration of antibody-assays into existing surveillance activities could improve exposure assessment, and may help to monitor the effectiveness of malaria control efforts and adapt elimination interventions. [ABSTRACT FROM AUTHOR]

Coronagraphic imaging of exoplanets and circumstellar environments using ground-based instruments on large telescopes is intrinsically limited by speckles induced by uncorrected aberrations. These aberrations originate from the imperfect correction of the atmosphere by an extreme adaptive optics system; from static optical defects; or from small opto-mechanical variations due to changes in temperature, pressure, or gravity vector. More than the speckles themselves, the performance of high-contrast imagers is ultimately limited by their temporal stability, since most post-processing techniques rely on difference of images acquired at different points in time. Identifying the origin of the aberrations and the timescales involved is therefore crucial to understanding the fundamental limits of dedicated high-contrast instruments. In previous works we demonstrated the use of a Zernike wavefront sensor called ZELDA for sensing non-common path aberrations (NCPA) in the VLT/SPHERE instrument. We now use ZELDA to investigate the stability of the instrumental aberrations using five long sequences of measurements obtained at high cadence on the internal calibration source. Our study reveals two regimes of decorrelation of the NCPA. The first, with a characteristic timescale of a few seconds and an amplitude of a few nanometers, is induced by a fast internal turbulence within the enclosure. The second is a slow quasi-linear decorrelation on the order of a few 10−3 nmrms s−1 that acts on timescales from minutes to hours. We use coronagraphic image reconstruction to demonstrate that these two NCPA contributions have a measurable impact on differences of images, and that the fast internal turbulence is a dominating term over to the slow linear decorrelation. We also use dedicated sequences where the derotator and atmospheric dispersion compensators emulate a real observation to demonstrate the importance of performing observations symmetric around the meridian, which minimizes speckle decorrelation, and therefore maximizes the sensitivity to point sources in difference of images. [ABSTRACT FROM AUTHOR]

Open Government Data (OGD) has become a widely employed tool by governments around the world to promote transparent and accountable policy-making. In the context of societal actors' ability to reuse such data, one of the most important features of ODG is its quality. Thus, through this research, we aim to address the level of data quality by introducing a new framework that constantly monitors and evaluates the OGD quality of Western Balkan (WB) National Open Data Portals. The advantage of the proposed framework is the integration on the portal level enabling information exposure about the quality dimension at any time. An additional value of the framework is the ability to provide recommendations with the intention of improving quality issues. The applicability and findings of the proposed framework are not limited to the WB and once contextualized that could be applied to other countries in the Eastern European that face similar data quality challenges. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of autologous lamellar keratoplasty for the treatment of feline corneal sequestrum (FCS). Procedure: The medical records of cats diagnosed with FCS that underwent autologous lamellar keratoplasty between 2012 and 2020 with a minimum of 2 months of follow‐up were reviewed. After keratectomy of FCS, a button adjacent to the corneal limbus was harvested on the same eye and sutured to the recipient bed. A nictitating membrane flap was left in place until the first recheck except for one patient. Postoperative treatment with topical and systemic antibiotics and systemic nonsteroidal anti‐inflammatory medications was prescribed. Follow‐up examinations were carried out 2 weeks, 1 month and 2 months post‐operatively and consisted of a complete ophthalmic examination. Results: A total of 35 cats (35 eyes) were included. The median follow‐up time was 3.2 months (range, 2–59 months). Brachycephalic cats were overrepresented (85.7%). The mean graft size was 6.5 mm (range, 6–9 mm). Minor complications consisting of melting and partial integration of the graft occurred in 2/35 eyes (5.7%). Recurrence was observed in 1/35 eyes (2.9%) and was managed by a superficial keratectomy. A good visual outcome was achieved in all eyes, and a faint or mild corneal opacification occurred in 15/35 (42.9%). Conclusions: Autologous lamellar keratoplasty is an effective treatment for FCS, providing good tectonic support to the affected cornea and resulting in good visual and cosmetic outcomes. These results should be verified in future prospective studies that include a larger number of cases and longer‐term follow‐up. [ABSTRACT FROM AUTHOR]

Combining high-contrast imaging with medium-resolution spectroscopy has been shown to significantly boost the direct detection of exoplanets. HARMONI, one of the first-light instruments to be mounted on ESO's future extremely large telescope (ELT), will be equipped with a single-conjugated adaptive optics system to reach the diffraction limit of the ELT in the H and K bands, a high-contrast module dedicated to exoplanet imaging, and a medium-resolution (up to R = 17 000) optical and near-infrared integral field spectrograph. When combined, these systems will provide unprecedented contrast limits at separations between 50 and 400 mas. This paper is aimed at estimating the capabilities of the HARMONI high-contrast module for the direct detection of young giant exoplanets. We use an end-to-end model of the instrument to simulate high-contrast observations performed with HARMONI, based on realistic observing scenarios and conditions. We then analyze these data with the so-called "molecule mapping" technique combined with a matched-filter approach in order to disentangle companions from the host star and tellurics and to increase the signal-to-noise ratio (S/N) of the planetary signal. We detected planets above 5σ at contrasts up to 16 mag and separations down to 75 mas in several spectral configurations of the instrument. We show that molecule mapping allows for the detection of companions up to 2.5 mag fainter compared to state-of-the-art high-contrast imaging techniques based on angular differential imaging. We also demonstrate that the performance is not strongly affected by the spectral type of the host star and we show that we are able to reach close sensitivities for the best three quartiles of observing conditions at Armazones, which means that HARMONI could be used in near-critical observations during 60 to 70% of telescope time at the ELT. Finally, we simulated planets from population synthesis models to further explore the parameter space that HARMONI and its high-contrast module will open up and compare this to the current high-contrast instrumentation. [ABSTRACT FROM AUTHOR]

The western subarctic Pacific exhibits major biological productivity fed by the Oyashio Current and its two source waters: Western Subarctic Water, which supplies nutrients from the subarctic Pacific, and cold Okhotsk Sea Intermediate Water (OSIW), which supplies iron from the Sea of Okhotsk. We created seasonal climatologies of water properties to understand how the long-term trend (~ 50 years) and 18.6-year tidal cycle affect the Oyashio Intermediate Water (OYW). We found that over the trend, decreased OSIW outflow due to weakening of North Pacific overturning modifies OYW in winter. Meanwhile, OSIW outflow increases (decreases) in strong (weak) tide years. We predict that the opposite effects of the trend and strong tide will lead to stagnation of OYW properties until the mid-2020s, followed by accelerated warming until the mid-2030s (weak tide). A predicted 1 °C increase in OYW temperature and 50% decrease in OSIW content between 1960 and 2040 potentially have significant impact on biological productivity and carbon drawdown in the North Pacific. [ABSTRACT FROM AUTHOR]

Atime series analysis of the sea surface height anomaly (SSHa) was conducted in the Kuril Basin of the Sea of Okhotsk. The mapping of the satellite-derived SSHa data was optimized to mitigate the effects of sea ice on the SSHa field during winter and early spring. Complex empirical orthogonal functions (CEOFs) were then used to analyze the SSHa field, revealing that the first three modes account for 55% of the signal variance. Mode 1 mainly represents the coherent variability trapped over the shelves all along the coastal regions and the Kuril Islands. Both seasonal and interannual variations are strongly correlated with the alongshore wind stress and can be well explained by an arrested topographic wave. Mode 3 is a propagating mode that exhibits trains of southwestward-propagating, high-amplitude anomalies. One possible mechanism for this is firstmode baroclinic Rossby waves, whose energy propagates from the Kuril Straits toward the Kuril Basin. However, mode 3 can be better interpreted as barotropic Rossby normal modes generated in the deep Kuril Basin. Mode 2 is a standing mode that may encompass the baroclinic variability in the basin. The monthly mean of the SSHa in the Kuril Basin is primarily governed by variability in mode 1, with mode 2 contributing to a lesser extent, and mode 3 being insignificant. [ABSTRACT FROM AUTHOR]

Background: Patient autonomy is central to the provision of respectful maternity care. Enabling women to make decisions free of discrimination and coercion, and respecting their privacy and confidentiality can contribute to positive childbirth experiences. This study aimed to deepen the understanding of how patient autonomy is reflected through social practices during intrapartum care in Benin. Methods: Semi-structured interviews with women and midwives, a focus-group discussion with women's birth companions, and non-participant observations in the delivery room were conducted within the frame of the ALERT research project. This study analysed data through a reflexive thematic analysis approach, in line with Braun and Clarke. Results: We identified two themes and five sub-themes. Patient autonomy was systemically suppressed over the course of birth as a result of the conditions of care provision, various forms of coercion and women's surrendering of their autonomy. Women used other care practices, such as alternative medicine and spiritual care, to counteract experiences of limited autonomy during intrapartum care. Conclusions: The results pointed to women's experiences of limited patient autonomy and their use of alternative and spiritual care practices to reclaim their patient autonomy. This study identified spiritual autonomy as an emergent dimension of patient autonomy. Increasing women's autonomy during childbirth may improve their experiences of childbirth, and the provision of quality and respectful maternity care. [ABSTRACT FROM AUTHOR]

Observations of circumstellar environments that look for the direct signal of exoplanets and the scattered light from disks have significant instrumental implications. In the past 15 years, major developments in adaptive optics, coronagraphy, optical manufacturing, wavefront sensing, and data processing, together with a consistent global system analysis have brought about a new generation of high-contrast imagers and spectrographs on large ground-based telescopes with much better performance. One of the most productive imagers is the Spectro-Polarimetic High contrast imager for Exoplanets REsearch (SPHERE), which was designed and built for the ESO Very Large Telescope (VLT) in Chile. SPHERE includes an extreme adaptive optics system, a highly stable common path interface, several types of coronagraphs, and three science instruments. Two of them, the Integral Field Spectrograph (IFS) and the Infra-Red Dual-band Imager and Spectrograph (IRDIS), were designed to efficiently cover the near-infrared range in a single observation for an efficient search of young planets. The third instrument, ZIMPOL, was designed for visible polarimetric observation to look for the reflected light of exoplanets and the light scattered by debris disks. These three scientific instruments enable the study of circumstellar environments at unprecedented angular resolution, both in the visible and the near-infrared. In this work, we thoroughly present SPHERE and its on-sky performance after four years of operations at the VLT. [ABSTRACT FROM AUTHOR]

Second-generation exoplanet imagers using extreme adaptive optics (ExAO) and coronagraphy have demonstrated their great potential for studying close circumstellar environments and for detecting new companions and helping to understand their physical properties. However, at very small angular separation, their performance in contrast is limited by several factors: diffraction by the complex telescope pupil (central obscuration and spiders) not perfectly canceled by the coronagraph, residual dynamic wavefront errors, chromatic wavefront errors, and wavefront errors resulting from noncommon path aberrations (NCPAs). These latter are differential aberrations between the visible wavefront sensing path of the ExAO system and the near-infrared science path in which the coronagraph is located. In a previous work, we demonstrated the use of a Zernike wavefront sensor called ZELDA for sensing NCPAs in the VLT/SPHERE exoplanet imager and their compensation with the high-order deformable mirror of the instrument. These early tests on the internal light source led to encouraging results for the attenuation of the quasi-static speckles at very small separation. In the present work, we move to the next step with the on-sky validation of NCPA compensation with ZELDA. With an improved procedure for the compensation of NCPAs, we start by reproducing previous results on the internal source. We show that the amount of aberration integrated between 1 and 15 cycles/pupil (c/p) is decreased by a factor of approximately five, which translates into a gain in raw contrast of between 2 and 3 at separations below 300 mas. On sky, we demonstrate that NCPA compensation works in closed loop, leading to an attenuation of the amount of aberration by a factor of approximately two. However, we identify a loss of sensitivity for the sensor that is only partly explained by the difference in Strehl ratio between the internal and on-sky measurements. Our simulations show that the impact of ExAO residuals on ZELDA measurements is negligible for integration times beyond a few tenths of a second. Coronagraphic imaging on sky is improved in raw contrast by a factor of 2.5 at most in the ExAO-corrected region. We use coronagraphic image reconstruction based on a detailed model of the instrument to demonstrate that both internal and on-sky raw contrasts can be precisely explained, and we establish that the observed performance after NCPA compensation is no longer limited by an improper compensation for aberration but by the current apodized-pupil Lyot coronagraph design. We finally conclude that a coronagraph upgrade combined to a proper NCPA compensation scheme could easily bring a gain in raw contrast of a factor of two to three below 200 mas. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses.Methods: Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. The pharmacokinetics of imiglucerase was analyzed using a population-pharmacokinetic model from a cohort of 31 patients with Gaucher disease type 1 who either started or were receiving long-term treatment with imiglucerase.Results: A pharmacokinetic analysis of imiglucerase showed a two-compartment model with a high peak followed by a two-phase exponential decay (fast phase half-life: 0.36 days; slow phase half-life: 9.7 days) leading to a median 1.4-fold increase in glucocerebrosidase intra-monocyte activity from the pre-treatment activity (p = 0.04). In patients receiving long-term treatment, for whom the imiglucerase dose per infusion was chosen on the basis of disease aggressiveness/response, imiglucerase clearance correlated with the administered dose. However, the residual glucocerebrosidase intra-monocyte activity value was dose independent, suggesting that the maintenance of imiglucerase residual activity is patient specific. Endogenous pre-treatment glucocerebrosidase intra-monocyte activity was the most informative single parameter for distinguishing patients without (n = 10) and with a clinical indication (n = 17) for starting enzyme replacement therapy (area under the receiver operating characteristic curve: 0.912; 95% confidence interval 0.8-1; p < 0.001), as confirmed also by a factorial analysis of mixed data.Conclusion: This study provides novel pharmacokinetic data that support current imiglucerase administration regimens and suggests the existence of a glucocerebrosidase activity threshold related to Gaucher disease type 1 aggressiveness. These findings can potentially improve Gaucher disease type 1 management algorithms and clinical decision making. [ABSTRACT FROM AUTHOR]

Abstract The seasonal variability of the hydrography and anticyclonic circulation in the Kuril Basin of the Sea of Okhotsk, from which the North Pacific ventilation originates, is studied from bi-monthly climatologies of temperature, salinity, dynamic height and current velocity. The subsurface hydrography of the Kuril Basin is characterized by the dominant role of fresh and cold waters transported by the East Sakhalin Current during winter and spring, and relatively warm and saline waters flowing with the Soya Warm Current. At the intermediate layer, the influence of dense shelf water is maximum from May to August, and this water mixes with surrounding waters in around half a year to form a well homogenized Okhotsk Sea Intermediate Water, the source of North Pacific ventilation. The anticyclonic circulation typical of the Kuril Basin exhibits a strong seasonality, being absent in winter and showing a maximum amplitude in summer. Its formation is mainly related to the dynamic response of isopycnals to wind forcing. A dynamic height maximum appears along the coastal regions from Sakhalin Island to the southern Kuril Straits in winter, likely migrates towards the Kuril Basin in March–April and forms the anticyclonic system between May and October. The dynamic height – and thus the flow field – is mainly determined by isopycnal displacement in and around the Kuril Basin, whereas advection of water masses has a negligible effect. Surface intensification and decay of the anticyclonic circulation seems to be related to other processes such as heat exchange with the atmosphere. Highlights • The anticyclonic circulation in the Kuril Basin exhibits a strong seasonality. • Its formation is related to a dynamic response of isopycnals to wind stress changes. • Isopycnal displacement is mainly responsible for dynamic height changes there. • Dense Shelf Water is found in May–August and Soya Current Water in July–October. • They mix to form a homogenized Okhotsk Sea Intermediate Water within half a year. [ABSTRACT FROM AUTHOR]

This study aimed to assess characteristics associated with infections due to carbapenem-resistant Enterobacteriaceae (CRE), producing (CPE) or not producing (non-CPE) carbapenemase, among hospitalised patients in 2014-2016 in France. Case-patients with CRE were compared to two control populations. In multivariate analysis comparing 160 CRE cases to 160 controls C1 (patients with a clinical sample positive for carbapenem-susceptible Enterobacteriaceae), five characteristics were linked to CRE: male gender (OR = 1.9; 95% CI = 1.3-3.4), travel in Asia (OR = 10.0; 95% CI = 1.1-91.2) and hospitalisation in (OR = 2.4; 95% CI = 1.3-4.4) or out of (OR = 4.4; 95% CI = 0.8-24.1) France in the preceding 12 months, infection in the preceding 3 months (OR = 3.0; 95% CI = 1.5-5.9), and antibiotic receipt between admission and inclusion (OR = 1.9; 95% CI = 1.0-3.3). In multivariate analysis comparing 148 CRE cases to 148 controls C2 [patients with culture-negative sample(s)], four characteristics were identified: prior infection (OR = 3.3; 95% CI = 1.6-6.8), urine drainage (OR = 3.0; 95% CI = 1.5-6.1) and mechanical ventilation (OR = 3.7; 95% CI = 1.1-13.0) during the current hospitalisation, and antibiotic receipt between admission and inclusion (OR = 6.6; 95% CI = 2.8-15.5). Univariate analyses comparing separately CPE cases to controls (39 CPE vs C1 and 36 CPE vs C2) and non-CPE cases to controls (121 non-CPE vs C1 and 112 non-CPE vs C2), concomitantly with comparison of CPE to non-CPE cases showed that only CPE cases were at risk of previous travel and hospitalisation abroad. This study shows that, among CRE, risk factors are different for CPE and non-CPE infection, and suggests that question patients about their medical history and lifestyle should help for early identification of patients at risk of CPE among patients with CRE. [ABSTRACT FROM AUTHOR]

Highlights • Flock mobility impacts on CH 4 can be modelled by taking into account feed diversity. • Flock mobility increased net CH 4 emissions of sheep farming systems. • Pastoral systems produced the highest lambs’ CH 4 emission per unit of product. • Ewes in sedentary systems produced the highest CH 4 emissions (kg/year). Abstract Ruminant livestock systems are significant sources of greenhouse gases (GHG). Livestock farming in regions with extreme climatic events have to face both scarcity and variability in feed resources. Herd mobility is a known major adaptation strategy to address seasonal availability of forage resources: it allows an increase in herd size, thereby improving labor productivity. The present study quantifies enteric methane (CH 4) emissions from French Mediterranean sheep farming systems, focusing on the use of diversified pastoral feed resources, and developing a calculator (Diversity of feed REsources and Enteric Methane emissions, DREEM). The DREEM calculator was developed to estimate at the animal level enteric CH 4 emissions (g/day) from empirical equations and be subsequently integrated, as a sub-table, into an economic and GHG (kg/year) balance model (Outil de Simulation du TRoupeau ovin ALaitant, OSTRAL) at the whole farm level. Several equations were taken from the literature to estimate enteric CH 4 emissions in DREEM calculator. Nature of forage and feed, animal feeding levels and performance were referenced according to the animal feeding system and tables in France and taking into account the French Mediterranean area studied. DREEM was used to estimate enteric CH 4 emissions from four sheep farming systems covering the main contrasting mobility and situations, from sedentary to highly mobile pastoral systems, in the French Mediterranean area. At the individual level, enteric CH 4 emissions (g/day) of ewes in the sedentary system were slightly higher than those of ewes in other systems. These differences were due mainly to differences in animal feeding level (intake / body weight) and feed resources characteristics. Overall, enteric CH 4 emissions of ewes and rams were slightly lower than French national inventory estimates. When enteric CH 4 emissions of lambs were expressed in g/kg of carcass, were lower in the less pastoral farming systems than in the other systems, because lambs’ average daily gains were higher. In double transhuming farming systems, lambs late slaughtering age led to lamb’s CH 4 contribution of 15% vs 2–5% in the other systems. Flock management, which depends on land use and ownership, greatly contributed to these results. [ABSTRACT FROM AUTHOR]

The effect of thermal mass on the salinity estimate from conductivity–temperature–depth (CTD) tags sensor mounted on marine mammals is documented, and a correction scheme is proposed to mitigate its impact. The algorithm developed here allows for a direct correction of the salinity data, rather than a correction of the sample’s conductivity and temperature. The amplitude of the thermal mass–induced error on salinity and its correction are evaluated via comparison between data from CTD tags and from Sea-Bird Scientific CTD used as a reference. Thermal mass error on salinity appears to be generally O(10−2) g kg−1, it may reach O(10−1) g kg−1, and it tends to increase together with the magnitude of the cumulated temperature gradient (THP) within the water column. The correction we propose yields an error decrease of up to ~60% if correction coefficients specific to a certain tag or environment are calculated, and up to 50% if a default value for the coefficients is provided. The correction with the default coefficients was also evaluated using over 22 000 in situ dive data from five tags deployed in the Southern Ocean and is found to yield significant and systematic improvements on the salinity data, including for profiles whose THP was weak and the error small. The correction proposed here yields substantial improvements in the density estimates, although a thermal mass–induced error in temperature measurements exists for very large THP and has yet to be corrected. [ABSTRACT FROM AUTHOR]

We present observations of the Herbig Ae star HD 169142 with the VLT/SPHERE instruments InfraRed Dual-band Imager and Spectrograph (IRDIS) (K1K2 and H2H3 bands) and the Integral Field Spectrograph (IFS) (Y, J and H bands). We detect several bright blobs at ∼180 mas separation from the star, and a faint arc-like structure in the IFS data. Our reference differential imaging (RDI) data analysis also finds a bright ring at the same separation. We show, using a simulation based on polarized light data, that these blobs are actually part of the ring at 180 mas. These results demonstrate that the earlier detections of blobs in the H and KS bands at these separations in Biller et al. as potential planet/substellar companions are actually tracing a bright ring with a Keplerian motion. Moreover, we detect in the images an additional bright structure at ∼93 mas separation and position angle of 355°, at a location very close to previous detections. It appears point-like in the YJ and K bands but is more extended in the H band. We also marginally detect an inner ring in the RDI data at ∼100 mas. Follow-up observations are necessary to confirm the detection and the nature of this source and structure. [ABSTRACT FROM AUTHOR]

We explore the multiplicity of exoplanet host stars with high-resolution images obtained with VLT/SPHERE. Two different samples of systems were observed: one containing low-eccentricity outer planets, and the other containing high-eccentricity outer planets. We find that 10 out of 34 stars in the high-eccentricity systems are members of a binary, while the proportion is 3 out of 27 for circular systems. Eccentric-exoplanet hosts are, therefore, significantly more likely to have a stellar companion than circular-exoplanet hosts. The median magnitude contrast over the 68 data sets is 11.26 and 9.25, in H and K, respectively, at 0.30 arcsec. The derived detection limits reveal that binaries with separations of less than 50 au are rarer for exoplanet hosts than for field stars. Our results also imply that the majority of high-eccentricity planets are not embedded in multiple stellar systems (24 out of 34), since our detection limits exclude the presence of a stellar companion. We detect the low-mass stellar companions of HD7449 and HD211847, both members of our high-eccentricity sample. HD7449B was already detected and our independent observation is in agreement with this earlier work. HD211847's substellar companion, previously detected by the radial velocity method, is actually a low-mass star seen face-on. The role of stellar multiplicity in shaping planetary systems is confirmed by this work, although it does not appear as the only source of dynamical excitation. [ABSTRACT FROM AUTHOR]

Pastoral farming systems have always adapted to the seasonal availability of forage resources and climate variability by moving animals. However, the role of animal mobility as a possible mitigating strategy in response to climate change has not been clearly documented. To understand this role, we investigated (i) the major methodological challenges linked to the diversity of grazing areas and other forage resources exploited by these systems and enteric emissions of methane; (ii) the impacts of grazing practices (carbon sequestration/emission) on soil and biomass carbon fluxes. We developed an approach based on two existing models (OSTRAL: Outil de Simulation du TRoupeau ovin ALlaitant and CASA: Carnegie Ames Stanford Approach) that we adapted and used in combination. This approach was applied to three French Mediterranean sheep and crop farming systems with different degrees of flock mobility (sedentary, single transhumance and double transhumance). The preliminary results produced by the whole farm model OSTRAL showed that two systems (sedentary and double transhumance) causing low carbon emissions. In the sedentary system, higher animal productivity offsets the increase in GHG emissions (in CO 2 eq) caused by feed production. In the pastoral system, grazing reduced total GHG emissions (in CO 2 eq). The CASA model proved to be useful to simulate the carbon balance under dynamic land cover in natural environments, whether used for grazing or not. This model can help assess the impact of grazing practices and carbon fluxes in systems linked to natural environments. The results of the first application showed that seasonal mobility of livestock increases the contribution of rangeland to feeding systems and improves the non-renewable energy balance of the system. It is thus extremely important to include the specificities of animals grazing in rangelands outside the structural limits of the farm when evaluating GHG emissions. [ABSTRACT FROM AUTHOR]

This paper focuses on the treatment of prudence by Adam Smith. Smith was one of the few philosophers to conceive of it as a moral virtue. Smithian prudence is the care of one's own happiness that is limited and ennobled, respectively, by the sense of justice and that of self-command. A reconstruction of Smith's view of prudence helps to clarify three central points in his thought: the interaction between the agent's economic and moral dimensions, the relationship between the self and the other, and the dialectical tension between partiality and impartiality. Furthermore, Smithian prudence is important, in itself, as an approach to the above-mentioned points that is still viable. These three points are recurrent crucial issues in the history of ethics. [ABSTRACT FROM AUTHOR]

This study presents amended procedures to process and map data collected by pressure-sensor-equipped inverted echo sounders (PIESs) in western boundary current regions. The modifications to the existing methodology, applied to observations of the Kuroshio from a PIES array deployed northeast of Luzon, Philippines, consist of substituting a hydrography-based mean travel time field for the PIES-based mean field and using two distinct gravest empirical mode (GEM) lookup tables across the front that separate water masses of South China Sea and North Pacific origin. In addition, this study presents a method to use time-mean velocities from acoustic Doppler current profilers (ADCPs) to reference (or 'level') the PIES-recorded pressures in order to obtain time series of absolute geostrophic velocity. Results derived from the PIES observations processed with the hydrography-based mean field and two GEMs are compared with hydrographic profiles sampled by Seagliders during the PIES observation period and with current velocity measured concurrently by a collocated ADCP array. The updated processing scheme leads to a 41% error decrease in the determination of the thermocline depth across the current, a 22% error decrease in baroclinic current velocity shear, and a 61% error decrease in baroclinic volume transports. The absolute volume transport time series derived from the leveled PIES array compares well with that obtained directly from the ADCPs with a root-mean-square difference of 3.0 Sv (1 Sv ≡ 106 m3 s-1), which is mainly attributed to the influence of ageostrophic processes on the ADCP-measured velocities that cannot be calculated from the PIES observations. [ABSTRACT FROM AUTHOR]

Sirius has always attracted a lot of scientific interest, especially after the discovery of a companion white dwarf at the end of the 19th century.Very early on, the existence of a potential third bodywas put forward to explain some of the observed properties of the system.We present new coronagraphic observations obtained with VLT/SPHERE (Very Large Telescope/Spectro- Polarimetric High-contrast Exoplanet REsearch) that explore, for the very first time, the innermost regions of the system down to 0.2 arcsec(0.5 au) from Sirius A. Our observations cover the near-infrared from 0.95 to 2.3 µmand they offer the best on-sky contrast ever reached at these angular separations. After detailing the steps of our SPHERE/IRDIFS data analysis, we present a robust method to derive detection limits for multispectral data from high-contrast imagers and spectrographs. In terms of raw performance, we report contrasts of 14.3 mag at 0.2 arcsec, ˜16.3 mag in the 0.4-1.0 arcsec range and down to 19 mag at 3.7 arcsec. In physical units, our observations are sensitive to giant planets down to 11 MJup at 0.5 au, 6-7 MJup in the 1-2 au range and ˜4 MJup at 10 au. Despite the exceptional sensitivity of our observations, we do not report the detection of additional companions around Sirius A. Using a Monte Carlo orbital analysis, we show that we can reject, with about 50 per cent probability, the existence of an 8 MJup planet orbiting at 1 au. [ABSTRACT FROM AUTHOR]

We consider the problem of finding the shortest path for a tethered robot in a planar environment with polygonal obstacles of n total vertices. The robot is attached to an anchor point by a tether of finite length. The robot can cross the tether; i.e., the tether can be self-intersecting. Neither the robot nor the tether may enter the interior of any obstacle. The initial tether configuration is given as a polyline of k vertices. If the tether is automatically retracted and kept taut, we present an O ( k n 2 log ⁡ n ) time algorithm to find the shortest path between the source and the destination point. This improves the previous O ( l k n 3 ) time algorithm [24] , where l is the number of loops in the initial tether configuration. If the tether can only be retracted while the robot backtracks along the tether, we present an algorithm to find the shortest path in O ( ( n + log ⁡ k ) log ⁡ n ) time. [ABSTRACT FROM AUTHOR]

Introduction: Étudier le profil épidémiologique, clinique et paraclinique de la PKAD chez des patients diagnostiqués au CNHU de Cotonou et évaluer l'intérêt d'un dépistage chez les patients à risque. Méthodes: Il s'agit d'une étude transversale comportant une revue de dossiers des patients cliniquement diagnostiqués PKAD à la clinique universitaire de néphrologie et d'hémodialyse du 1er janvier 2000 au 31 janvier 2011, et une enquête familiale chez les patients où le diagnostic de PKAD a été confirmé entre le 1er février et le 31 Août 2011.Un séquençage à la recherche de mutations dans les gènes de la Polycystine 1 et 2 a été réalisé chez les cas index. Résultats: L'incidence hospitalière de la PKAD était de 7,8 cas par an. Le dépistage familial avait permis d'examiner 99 membres de 22 familles et de confirmer 14 cas de PKAD. L'âge moyen des patients était de 45,6±12,8ans. Le signe physique le plus fréquent était l'hypertension artérielle (HTA (83%). Une insuffisance rénale chronique était observée dans 75% des cas. Le séquençage direct avait permis de mettre en évidence 7 nouvelles mutations dont 02 mutations dans les gènes PKD2 et 5 dans PKD1. Conclusion: La PKAD relativement fréquente, présente de nouvelles mutations chez les patients diagnostiqués au CNHU de Cotonou. Le conseil génétique est particulièrement indiqué dans les familles où la maladie rénale a débuté précocement. [ABSTRACT FROM AUTHOR]

Context. Young, nearby stars are ideal targets for direct imaging searches for giant planets and brown dwarf companions. After the first-imaged planet discoveries, vast efforts have been devoted to the statistical analysis of the occurence and orbital distributions of giant planets and brown dwarf companions at wide (≥5-6 AU) orbits. Aims. In anticipation of the VLT/SPHERE planet-imager, guaranteed-time programs, we have conducted a preparatory survey of 86 stars between 2009 and 2013 to identify new faint comoving companions to ultimately analyze the occurence of giant planets and brown dwarf companions at wide (10-2000 AU) orbits around young, solar-type stars. Methods. We used NaCo at VLT to explore the occurrence rate of giant planets and brown dwarfs between typically 0.1 and 8". Diffraction-limited observations in H-band combined with angular differential imaging enabled us to reach primary star-companion brightness ratios as small as 10-6 at 1.5". Repeated observations at several epochs enabled us to discriminate comoving companions from background objects. Results. During our survey, twelve systems were resolved as new binaries, including the discovery of a new white dwarf companion to the star HD?8049. Around 34 stars, at least one companion candidate was detected in the observed field of view. More than 400 faint sources were detected; 90% of them were in four crowded fields. With the exception of HD?8049?B, we did not identify any new comoving companions. The survey also led to spatially resolved images of the thin debris disk around HD?61005 that have been published earlier. Finally, considering the survey detection limits, we derive a preliminary upper limit on the frequency of giant planets for the semi-major axes of [10, 2000] AU: typically less than 15% between 100 and 500 AU and less than 10% between 50 and 500 AU for exoplanets that are more massive than 5 MJup and 10 MJup respectively, if we consider a uniform input distribution and a confidence level of 95%. Conclusions. The results from this survey agree with earlier programs emphasizing that massive, gas giant companions on wide orbits around solar-type stars are rare. These results will be part of a broader analysis of a total of ~210 young, solar-type stars to bring further statistical constraints for theoretical models of planetary formation and evolution. [ABSTRACT FROM AUTHOR]

Context. The new planet finder for the Very Large Telescope (VLT), the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE), just had its first light in Paranal. A dedicated instrument for the direct detection of planets, SPHERE, is composed of a polametric camera in visible light, the Zurich IMager POLarimeter (ZIMPOL), and two near-infrared sub-systems: the Infra-Red Dual-beam Imager and Spectrograph (IRDIS), a multi-purpose camera for imaging, polarimetry, and long-slit spectroscopy, and the integral field spectrograph (IFS), an integral field spectrograph. Aims. We present the results obtained from the analysis of data taken during the laboratory integration and validation phase, after the injection of synthetic planets. Since no continuous field rotation could be performed in the laboratory, this analysis presents results obtained using reduction techniques that do not use the angular di erential imaging (ADI) technique. Methods. To perform the simulations, we used the instrumental point spread function (PSF) and model spectra of L and T-type objects scaled in contrast with respect to the host star.We evaluated the expected error in astrometry and photometry as a function of the signal to noise of companions, after spectral di erential imaging (SDI) reduction for IRDIS and spectral deconvolution (SD) or principal component analysis (PCA) data reductions for IFS. Results. We deduced from our analysis, for example, that βPicb, a 12 Myr old planet of ∼10 MJup and semi-major axis of 9-10 AU, would be detected with IRDIS with a photometric error of 0.16 mag and with a relative astrometric position error of 1.1 mas.With IFS, we could retrieve a spectrum with error bars of about 0.15 mag on each channel and astrometric relative position error of 0.6 mas. For a fainter object such as HR8799d, a 13 MJup planet at a distance of 27 AU, IRDIS could obtain a relative astrometric error of 3 mas. [ABSTRACT FROM AUTHOR]

Endometriosis is defined as the presence of endometrial-type mucosa outside the uterine cavity. Of the proposed pathogenic theories (retrograde menstruation, coelomic metaplasia and Mullerian remnants), none explain all the different types of endometriosis. According to the most convincing model, the retrograde menstruation hypothesis, endometrial fragments reaching the pelvis via transtubal retrograde flow, implant onto the peritoneum and abdominal organs, proliferate and cause chronic inflammation with formation of adhesions. The number and amount of menstrual flows together with genetic and environmental factors determines the degree of phenotypic expression of the disease. Endometriosis is estrogen-dependent, manifests during reproductive years and is associated with pain and infertility. Dysmenorrhoea, deep dyspareunia, dyschezia and dysuria are the most frequently reported symptoms. Standard diagnosis is carried out by direct visualization and histologic examination of lesions. Pain can be treated by excising peritoneal implants, deep nodules and ovarian cysts, or inducing lesion suppression by abolishing ovulation and menstruation through hormonal manipulation with progestins, oral contraceptives and gonadotropin-releasing hormone agonists. Medical therapy is symptomatic, not cytoreductive; surgery is associated with high recurrence rates. Although lesion eradication is considered a fertility-enhancing procedure, the benefit on reproductive performance is moderate. Assisted reproductive technologies constitute a valid alternative. Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer, but preventive interventions are feasible. [ABSTRACT FROM AUTHOR]

We show that $$\mathbb {R}^3$$ can be packed at a density of $$0.222\ldots $$ with tori whose minor radius goes to zero. Furthermore, we show that the same torus arrangement yields an asymptotically optimal number of pairwise-linked tori. [ABSTRACT FROM AUTHOR]

Abstract: This study examines the evolution of the Kuroshio Tropical Water (KTW) from the Luzon Strait to the I-Lan Ridge northeast of Taiwan. Historical conductivity temperature depth (CTD) profiles are analyzed using a method based on the calculation of the root mean square (rms) difference of the salinity along isopycnals. In combination with analysis of the distribution of the salinity maximum, this method enables water masses in the Kuroshio and the vicinity, to be tracked and distinguished as well as the detection of the areas where water masses are modified. Vertical and horizontal eddy diffusivities are then calculated from hydrographic and current velocity data to elucidate the dynamics underlying the KTW interactions with the surrounding water masses. Changes in KTW properties mainly occur in the southern half of the Luzon Strait, while moderate variations are observed east of Taiwan on the right flank of the Kuroshio. In spite of a front dividing the KTW from the South China Sea Tropical Water (SCSTW) on Kuroshio׳s western side, mixing between these two water masses seemingly occurs in the Luzon Strait. These water masses׳ interaction is not evident east of Taiwan. The estimation of eddy diffusivities yields high horizontal diffusivities (K h ~102 m2 s−1) all along the Kuroshio path, due to the high current shear along the Kuroshio׳s flanks. The vertical diffusivity approaches 10−3 m2 s−1, with the highest values in the southern Luzon Strait. Instabilities generated when the Kuroshio encounters the rough topography of this region may enhance both vertical and horizontal diffusivities there. [Copyright &y& Elsevier]

Abstract: We focus on families of bipartitions, i.e. set partitions consisting of at most two components. A family of bipartitions is a separating family for a set if every two elements in the set are separated by some bipartition. In this paper we enumerate separating families of arbitrary size. We furthermore enumerate inclusion-wise minimal separating families of minimum and maximum sizes. [Copyright &y& Elsevier]

Breakthrough direct detections of planetary companions orbiting A-type stars confirm the existence of massive planets at relatively large separations, but dedicated surveys are required to estimate the frequency of similar planetary systems. To measure the first estimation of the giant exoplanetary systems frequency at large orbital separation around A-stars, we have conducted a deep-imaging survey of young (8-400 Myr), nearby (19-84 pc) A- and F-stars to search for substellar companions in the ∼10-300 AU range. The sample of 42 stars combines all A-stars observed in previous AO planet search surveys reported in the literature with new AO observations from VLT/NaCo and Gemini/NIRI. It represents an initial subset of the International Deep Planet Survey (IDPS) sample of stars covering M- to B-stars. The data were obtained with diffraction-limited observations in H- and Ks-band combined with angular differential imaging to suppress the speckle noise of the central stars, resulting in typical 5σ detection limits in magnitude difference of 12 mag at 1" , 14 mag at 2" and 16 mag at 5" which is sufficient to detect massive planets. A detailed statistical analysis of the survey results is performed using Monte Carlo simulations. Considering the planet detections, we estimate the fraction of A-stars having at least one massive planet (3-14 MJup) in the range 5-320 AU to be inside 5.9-18.8% at 68% confidence, assuming a flat distribution for the mass of the planets. By comparison, the brown dwarf (15-75 MJup) frequency for the sample is 2.0-8.9% at 68% confidence in the range 5-320 AU. Assuming power law distributions for the mass and semimajor axis of the planet population, the AO data are consistent with a declining number of massive planets with increasing orbital radius which is distinct from the rising slope inferred from radial velocity (RV) surveys around evolved A-stars and suggests that the peak of the massive planet population around A-stars may occur at separations between the ranges probed by existing RV and AO observations. Finally, we report the discovery of three new close M-star companions to HIP 104365 and HIP 42334. [ABSTRACT FROM AUTHOR]

The ABO blood group influences susceptibility to severe Plasmodium falciparum malaria. Recent evidence indicates that the protective effect of group O operates by virtue of reduced rosetting of infected red blood cells (iRBCs) with uninfected RBCs. Rosetting is mediated by a subgroup of PfEMP1 adhesins, with RBC binding being assigned to the N-terminal DBL1α1 domain. Here, we identify the ABO blood group as the main receptor for VarO rosetting, with a marked preference for group A over group B, which in turn is preferred to group O RBCs. We show that recombinant NTS-DBL1α1 and NTS-DBL1α1- CIDR1γ reproduce the VarO-iRBC blood group preference and document direct binding to blood group trisaccharides by surface plasmon resonance. More detailed RBC subgroup analysis showed preferred binding to group A1, weaker binding to groups A2 and B, and least binding to groups Ax and O. The 2.8 Å resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1α1-CIDR1γ, reveals extensive contacts between the DBL1α1 and CIDR1γ and shows that the NTS-DBL1α1 hinge region is essential for RBC binding. Computer docking of the blood group trisaccharides and subsequent site-directed mutagenesis localized the RBC-binding site to the face opposite to the heparin-binding site of NTS-DBLα1. RBC binding involves residues that are conserved between rosette-forming PfEMP1 adhesins, opening novel opportunities for intervention against severe malaria. By deciphering the structural basis of blood group preferences in rosetting, we provide a link between ABO blood grouppolymorphisms and rosette-forming adhesins, consistent with the selective role of falciparum malaria on human genetic makeup. [ABSTRACT FROM AUTHOR]

Background: Clinical features, complications and treatments of Gaucher's disease (GD), a rare autosomal.recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described. Methods: All patients with known GD, living in France, with ≥1 consultations (1980-2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009-2010) patients; and patients treated during 2009-2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables. Results: Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal.lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0-77) and 22 (0-84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1-67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson' disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009.2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%-26.5%) and 19.8% (13.5%-26.1%). Conclusion: This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment. [ABSTRACT FROM AUTHOR]

The clonally variant Plasmodium falciparum PfEMP1 adhesin is a virulence factor and a prime target of humoral immunity. It is encoded by a repertoire of functionally differentiated var genes, which display architectural diversity and allelic polymorphism. Their serological relationship is key to understanding the evolutionary constraints on this gene family and rational vaccine design. Here, we investigated the Palo Alto/VarO and IT4/R29 and 3D7/PF13_003 parasites lines. VarO and R29 form rosettes with uninfected erythrocytes, a phenotype associated with severe malaria. They express an allelic Cys2/ group A NTS-DBL1α1 PfEMP1 domain implicated in rosetting, whose 3D7 ortholog is encoded by PF13_0003. Using these three recombinant NTS-DBL1α1 domains, we elicited antibodies in mice that were used to develop monovariant cultures by panning selection. The 3D7/PF13_0003 parasites formed rosettes, revealing a correlation between sequence identity and virulence phenotype. The antibodies cross-reacted with the allelic domains in ELISA but only minimally with the Cys4/group B/C PFL1955w NTS-DBL1a. By contrast, they were variant-specific in surface seroreactivity of the monovariant-infected red cells by FACS analysis and in rosette-disruption assays. Thus, while ELISA can differentiate serogroups, surface reactivity assays define the more restrictive serotypes. Irrespective of cumulated exposure to infection, antibodies acquired by humans living in a malaria-endemic area also displayed a variant-specific surface reactivity. Although seroprevalence exceeded 90% for each rosetting line, the kinetics of acquistion of surface-reactive antibodies differed in the younger age groups. These data indicate that humans acquire an antibody repertoire to non-overlapping serotypes within a serogroup, consistent with an antibody-driven diversification pressure at the population level. In addition, the data provide important information for vaccine design, as production of a vaccine targeting rosetting PfEMP1 adhesins will require engineering to induce variant-transcending responses or combining multiple serotypes to elicit a broad spectrum of immunity. [ABSTRACT FROM AUTHOR]

In recent years, there has been intensive research into the direct detection of exoplanets. Data obtained in the future with high-contrast imaging instruments, optimized for the direct detection of giant planets, may be strongly limited by speckle noise. Specific observing strategies and data analysis methods, such as angular and spectral differential imaging, are required to attenuate the noise level and possibly to detect the flux of faint planets. Even though these methods are very efficient at suppressing the speckles, the photometry of faint planets is dominated by the speckle residuals. The determination of the effective temperature and surface gravity of the detected planets from photometric measurements in different bands is then limited by the photometric error on the planet flux. In this paper, we investigate this photometric error and the consequences on the determination of the physical parameters of the detected planets. We perform detailed end-to-end simulation with thecaos-based software package for spectro-polarimetric high-contrast exoplanet research (SPHERE) to obtain realistic data representing typical observing sequences in the and Ks bands with a high-contrast imager. The simulated data are used to measure the photometric accuracy as a function of contrast for planets detected with angular and spectral+angular differential methods. We apply this empirical accuracy to study the characterization capabilities of a high-contrast differential imager. We show that the expected photometric performances will allow the detection and characterization of exoplanets down to a Jupiter mass at angular separations of 1.0 and 0.2 arcsec, respectively, around high-mass and low-mass stars with two observations in different filter pairs. We also show that the determination of the physical parameters of the planets from photometric measurements in different filter pairs is essentially limited by the error on the determination of the surface gravity. [ABSTRACT FROM AUTHOR]

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition. [ABSTRACT FROM AUTHOR]

M. Viganò, T. Dengler, M.F. Mattei, A. Poncelet, J. Vanhaecke, E. Vermes, R. Kleinloog, Y. Li, Y. Gezahegen, J.F. Delgado, on behalf of the RAD A2411 Study Investigators. Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate mofetil in de novo cardiac transplant recipients: a randomized, multicenter study. Transpl Infect Dis 2010: 12: 23–30. All rights reserved Cytomegalovirus (CMV) is a major cause of infectious complications following cardiac transplantation, severely affecting short- and long-term outcomes. A 12-month, multicenter, randomized, open-label study in de novo cardiac transplant patients was undertaken to compare the efficacy, renal function, and safety of everolimus plus reduced cyclosporine versus mycophenolate mofetil (MMF) plus standard cyclosporine (ClinicalTrials.gov NCT00150046). CMV-specific data was prospectively collected on infections, laboratory evidence, CMV syndrome, and CMV disease. In total, 176 patients were randomized (everolimus 92; MMF 84). Use of CMV prophylaxis was similar between groups (everolimus 20.8%; MMF 24.0%). Patients in the everolimus arm had a significantly lower incidence of any CMV event (8.8% versus 32.5% with MMF, P<0.001), CMV infection as an adverse event (4.4% versus 16.9%, P=0.011), laboratory evidence of CMV (antigenemia 7.7% versus 27.7%, P<0.001; polymerase chain reaction assay 2.2% versus 12.0%, P=0.015), and CMV syndrome (1.1% versus 8.4%, P=0.028). In the donor (D)+/recipient (R)+and D−/R+ subgroups, even after adjusting for use of prophylaxis, the CMV event rate remained significantly lower with everolimus than with MMF ( P=0.0015 and P=0.0381, respectively). In conclusion, de novo cardiac transplant recipients experienced lower rates of CMV infection, CMV syndrome, or organ involvement on an everolimus-based immunosuppressant regimen compared with MMF. [ABSTRACT FROM AUTHOR]

Background: Methyl 2-octynoate is a synthetic fragrance which was first described to have sensitizing properties in 1935. It is one of the 26 fragrances to be labelled on the ingredient list according to current European cosmetics regulation. Objectives: To report the experience with patch testing with methyl 2-octynoate 1% and 2% in pet. Methods: 230 eczema patients were consecutively patch tested with 1% methyl 2-octynoate at department of Dermato-allergology Gentofte Hospital, Denmark and 120 eczema patients were consecutively patch tested with 2% M2O in Finn Chambers® at the Départment de Dermatologie, CHU Saint Jacques, France. Results: Three cases of active sensitization were observed. 2 (0.87%) of the 230 Danish subjects tested with 1% in pet. and of the 120 French subjects patch tested with 2% in pet. 1 (0.83%). There was no statistical difference in active sensitization between the two groups ( P = 0.72). Allergic contact dermatitis was observed in two patients (1.67%) in the French group and none in the Danish group. Conclusion: Contact allergy to methyl 2-octynoate was frequently seen when patch testing with 2% in pet. However, active sensitization was also observed, when patch testing with concentrations of 1% and 2% methyl 2-octynoate. The patch test concentration should be below 1% in pet., but a safe concentration remains to be defined. [ABSTRACT FROM AUTHOR]

Background: The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection. Methods: Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTSDBL1α1, CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children. Results: Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α1. None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies. Conclusions: Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play. [ABSTRACT FROM AUTHOR]

This paper revisits the thermal mass inertia correction of Sea-Bird Electronics, Inc., (SBE4) conductivity probes for the calculation of salinity. In particular, it is shown that the standard parameters recommended for the correction method are not satisfactory for the data collected during recent campaigns at sea. A method, based on Morison et al., is proposed to determine optimal values for the correction parameters from selected datasets. Values valid for general cases are then proposed that yield significant improvements in the reduction of salinity errors that occur during the upcasts and downcasts of CTD profilers in areas with sharp thermoclines. The sources of the differences found between the recommended coefficient values and the ones proposed here are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Severe Plasmodium falciparum malaria in African children is associated with high peripheral parasite densities and high rate of rosette-forming parasites. To explore the relationship between rosette formation and parasite density in vivo, we compared the multiplication rate of a rosette-forming variant (varO) of the Palo Alto line with a sibling non-rosetting variant (varR) in splenectomized Saimiri monkeys. The multiplication rate of varO parasites was 1.5-fold higher than that of the varR variant. This indicates that rosetting is indeed associated with high parasite multiplication efficiency in vivo and, as such, may contribute to the high parasite densities observed in severe malaria. [Copyright &y& Elsevier]

Objectives: To assess recent trends in the prevalence of Down syndrome and the proportion of cases with a prenatal diagnosis in the Parisian population. Patients and methods: Four hundred and ninety-nine cases of Down syndrome were registered by the Paris Registry of Congenital Anomalies during the period 2001–2005. All cases with prenatal diagnosis were confirmed by cytogenetic examination. We analyzed trends in the total and live birth prevalence, the proportion of cases with a prenatal diagnosis and those with a pregnancy termination, as well as gestational age at diagnosis and termination. Analyses were stratified by maternal age and trends were tested by the Cochran-Armitage test and Anova. Results: Total prevalence of Down syndrome remained high (37.6 per 10,000 births, 95%CI 34.2–40.9) during this period because of advanced maternal age in Paris. The proportion of cases with a prenatal diagnosis (overall average 85.5%, 95% CI 81.8–88.1), and live birth prevalence of Down syndrome (7.1 per 10,000 live births, 95%CI 5.7–8.6) have remained fairly stable over time. The great majority of women (95% CI 95% 92.7–96.9) opted for a pregnancy termination following a prenatal diagnosis of Down syndrome. A trend towards an earlier gestational age at prenatal diagnosis was noted among women less than 30 years of age. Discussion and conclusion: It is important to continue to evaluate changes in the prenatal diagnosis of Down syndrome, notably in view of potential changes in screening practices and policies, and particularly if a first trimester strategy is adopted following recent recommendation by the “Haute Autorité de santé”. [Copyright &y& Elsevier]

Abstract: Cosmetics are products, which by definition “…must not damage human health in the normal conditions of use”. However, unwanted effects do occur, the best known being cutaneous and allergic reactions. The dermatology-allergy specialist is thus the first to be concerned with cosmetovigilance. In 1966, the Groupe d’études et de recherche en dermato-allergologie (GERDA) created a vigilance network concerned with cutaneous allergic incidents [Réseau de vigilance sur les accidents allergiques cutanés (REVIDAL)], the REVIDAL GERDA, which acts as a coordinator for cosmetovigilance. In 2004, a public cosmetovigilance committee was created; all serious adverse effects or those appearing to be serious were to be reported immediately to the Agence française de sécurité sanitaire des produits de santé (AFSSAPS) by health professionals who observed them. Manufacturers are required to participate in this public cosmetovigilance. They have a similar responsibility via the Direction générale de la concurrence et de la consommation (DGCCRF) to report to AFSSAPS the list of their products which contain substances for which there is a serious doubt. This means that cosmetovigilance requires collection of cases; it will work well only if reports are made regularly. The physician who reports cases improves the management of his patients and participates in Public Health actions. This type of cosmetovigilance will extend to all EU countries. Reports by consumers should be possible, but they will be encouraged to consult a doctor before doing so. [Copyright &y& Elsevier]

Objectives: We assessed socioeconomic differences in probabilities of prenatal diagnoses of Down syndrome and continuation of pregnancies after such diagnoses, along with the effects of these differences on disparities in live-birth prevalences of Down syndrome. Methods: Using population-based data derived from 1433 cases of Down syndrome and 3731 control births, we assessed age-adjusted effects of maternal occupation and geographic origin on prenatal diagnoses, as well as overall and live-birth odds, of Down syndrome. Results: Maternal occupation and geographic origin had significant effects on the probability of a prenatal diagnosis of Down syndrome and on continuation of pregnancy after such a diagnosis. Women in lower-status occupational categories had higher odds of delivering a live-born infant with Down syndrome. In comparison with women in the highest-status occupational category, the age-adjusted odds ratio for a Down syndrome live birth among women without an occupation was 2.4 (95% confidence interval [CI] = 1.7, 3.3). By contrast, there were no disparities in age-adjusted overall likelihood of Down syndrome. Conclusions: Socioeconomic differences in use of prenatal testing have created disparities in the live-birth prevalence of Down syndrome. Overall Down syndrome risk does not vary according to socioeconomic status. [ABSTRACT FROM AUTHOR]