Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study.

BackgroundThe p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease.MethodsTo expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events.ResultsIn p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3%).Conclusionp.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males

Distribution of subglacial sediments across the Wilkes Subglacial Basin, East Antarctica

Topography, sediment distribution, and heat flux are all key boundary conditions governing the dynamics of the East Antarctic Ice Sheet (EAIS). EAIS stability is most at risk in Wilkes Land across vast expanses of marine-based catchments including the 1400 km × 600 km expanse of the Wilkes Subglacial Basin (WSB) region. Data from a recent regional aerogeophysical survey (Investigating the Cryospheric Evolution of the Central Antarctic Plate (ICECAP)/IceBridge) are combined with two historical surveys (Wilkes basin/Transantarctic Mountains System Exploration-Ice-house Earth: Stability or DYNamism? (WISE-ISODYN) and Wilkes Land Transect (WLK)) to improve our understanding of the vast subglacial sedimentary basins impacting WSB ice flow and geomorphology across geologic time. Analyzing a combination of gravity, magnetic and ice-penetrating radar data, we present the first detailed subglacial sedimentary basin model for the WSB that defines distinct northern and southern subbasin isopachs with average sedimentary basin thicknesses of 1144 m ± 179 m and 1623 m ± 254 m, respectively. Notably, more substantial southern subbasin sedimentary deposition in the WSB interior supports a regional Wilkes Land hypothesis that basin-scale ice flow and associated glacial erosion is dictated by tectonic basement structure and the inherited geomorphology of preglacial fluvial networks. Orbital, temperate/polythermal glacial cycles emanating from adjacent alpine highlands during the early Miocene to late Oligocene likely preserved critical paleoclimatic data in subglacial sedimentary strata. Substantially thinner northern WSB subglacial sedimentary deposits are generally restricted to fault-controlled, channelized basins leading to prominent outlet glacier catchments suggesting a more dynamic EAIS during the Pliocene

OxyCAP UK: Oxyfuel Combustion - academic Programme for the UK

The OxyCAP-UK (Oxyfuel Combustion - Academic Programme for the UK) programme was a £2 M collaboration involving researchers from seven UK universities, supported by E.On and the Engineering and Physical Sciences Research Council. The programme, which ran from November 2009 to July 2014, has successfully completed a broad range of activities related to development of oxyfuel power plants. This paper provides an overview of key findings arising from the programme. It covers development of UK research pilot test facilities for oxyfuel applications; 2-D and 3-D flame imaging systems for monitoring, analysis and diagnostics; fuel characterisation of biomass and coal for oxyfuel combustion applications; ash transformation/deposition in oxyfuel combustion systems; materials and corrosion in oxyfuel combustion systems; and development of advanced simulation based on CFD modelling

Radar sounding evidence for buried glaciers in the southern mid-latitudes of Mars

Lobate features abutting massifs and escarpments in the middle latitudes of Mars have been recognized in images for decades, but their true nature has been controversial, with hypotheses of origin such as ice-lubricated debris flows or glaciers covered by a layer of surface debris. These models imply an ice content ranging from minor and interstitial to massive and relatively pure. Soundings of these deposits in the eastern Hellas region by the Shallow Radar on the Mars Reconnaissance Orbiter reveal radar properties entirely consistent with massive water ice, supporting the debris-covered glacier hypothesis. The results imply that these glaciers formed in a previous climate conducive to glaciation at middle latitudes. Such features may collectively represent the most extensive nonpolar ice yet recognized on Mars

Asteroids Were Born Big

How big were the first planetesimals? We attempt to answer this question by conducting coagulation simulations in which the planetesimals grow by mutual collisions and form larger bodies and planetary embryos. The size frequency distribution (SFD) of the initial planetesimals is considered a free parameter in these simulations, and we search for the one that produces at the end objects with a SFD that is consistent with asteroid belt constraints. We find that, if the initial planetesimals were small (e.g. km-sized), the final SFD fails to fulfill these constraints. In particular, reproducing the bump observed at diameter D~100km in the current SFD of the asteroids requires that the minimal size of the initial planetesimals was also ~100km. This supports the idea that planetesimals formed big, namely that the size of solids in the proto-planetary disk ``jumped'' from sub-meter scale to multi-kilometer scale, without passing through intermediate values. Moreover, we find evidence that the initial planetesimals had to have sizes ranging from 100 to several 100km, probably even 1,000km, and that their SFD had to have a slope over this interval that was similar to the one characterizing the current asteroids in the same size-range. This result sets a new constraint on planetesimal formation models and opens new perspectives for the investigation of the collisional evolution in the asteroid and Kuiper belts as well as of the accretion of the cores of the giant planets.Comment: Icarus (2009) in pres

The Market Performance of Socially Responsible Investment during Periods of the Economic Cycle - Illustrated Using the Case of FTSE

The debate about socially responsible investment (SRI) portfolio performance compared with its non-SRI counterparts remains inconclusive. This paper contributes to the debate by adding a new approach, examining the issue of a full economic circle through economic boom, recession and recovery. We compare stock performance of two value-weighted investment portfolios: FTSE4Good (SRI portfolios) and FTSE 350 (conventional portfolios) from 2004 to 2011 including 2007 to 2009 financial crash. The results indicate the SRI portfolio performed better and recovered its value quicker in post-crisis than the non-SRI portfolio, indicating that SRI portfolios are more resilient to economic turmoil and market shocks

Towards Eliminating Bias in Cluster Analysis of TB Genotyped Data

The relative contributions of transmission and reactivation of latent infection to TB cases observed clinically has been reported in many situations, but always with some uncertainty. Genotyped data from TB organisms obtained from patients have been used as the basis for heuristic distinctions between circulating (clustered strains) and reactivated infections (unclustered strains). Naïve methods previously applied to the analysis of such data are known to provide biased estimates of the proportion of unclustered cases. The hypergeometric distribution, which generates probabilities of observing clusters of a given size as realized clusters of all possible sizes, is analyzed in this paper to yield a formal estimator for genotype cluster sizes. Subtle aspects of numerical stability, bias, and variance are explored. This formal estimator is seen to be stable with respect to the epidemiologically interesting properties of the cluster size distribution (the number of clusters and the number of singletons) though it does not yield satisfactory estimates of the number of clusters of larger sizes. The problem that even complete coverage of genotyping, in a practical sampling frame, will only provide a partial view of the actual transmission network remains to be explored

ART Suppresses Plasma HIV-1 RNA to a Stable Set Point Predicted by Pretherapy Viremia

Current antiretroviral therapy is effective in suppressing but not eliminating HIV-1 infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-1 infection. We therefore investigated the level of plasma HIV-1 RNA in patients with viremia suppressed to less than 50–75 copies/ml on standard protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy using a new, real-time PCR-based assay for HIV-1 RNA with a limit of detection of one copy of HIV-1 RNA. Single copy assay results revealed that >80% of patients on initial antiretroviral therapy for 60 wk had persistent viremia of one copy/ml or more with an overall median of 3.1 copies/ml. The level of viremia correlated with pretherapy plasma HIV-1 RNA but not with the specific treatment regimen. Longitudinal studies revealed no significant decline in the level of viremia between 60 and 110 wk of suppressive antiretroviral therapy. These data suggest that the persistent viremia on current antiretroviral therapy is derived, at least in part, from long-lived cells that are infected prior to initiation of therapy

Report on the STECF Expert Working Group 17-12 Fisheries Dependent Information: ‘New-FDI’

The STECF expert working group (EWG) on Fisheries Dependant Information (FDI) took place in JRC, Ispra from 23 to 27 October 2017 to review the data transmitted by Member States under a new data call (‘New-FDI’). The new data call specification was designed with three broad aims in mind i) Compatibility between the New-FDI data and the data held in the Fleet Economic database. ii) Ability to encompass all EU registered vessels including those from the Mediterranean, Black Sea and external waters fleets. iii) Ability to assess effects of management measures. The main purpose of the EWG was to judge if the call specification was appropriate to accomplish the above aims and to consider any difficulties encountered by member states in fulfilling the data call. Two terms of reference also allowed trial analyses to be conducted of a type relevant to the third broad aim. The EWG addressed all Terms of Reference during the meeting and drew conclusions on the modifications required for the New-FDI data call going forwards. Prior to the EWG it had been agreed by STECF Bureau that the report of the meeting would not be presented to STECF for approval as an STECF report but published separately (as a JRC technical report). This report therefore presents the data, methods observations and findings of an EWG of the STECF but the findings presented in this report do not necessarily constitute the opinion of the STECF or reflect the views of the European Commission and in no way anticipate the Commission’s future policy in this area.JRC.D.2-Water and Marine Resource

Synchronous Symmetry Breaking in Neurons with Different Neurite Counts

As neurons develop, several immature processes (i.e., neurites) grow out of the cell body. Over time, each neuron breaks symmetry when only one of its neurites grows much longer than the rest, becoming an axon. This symmetry breaking is an important step in neurodevelopment, and aberrant symmetry breaking is associated with several neuropsychiatric diseases, including schizophrenia and autism. However, the effects of neurite count in neuronal symmetry breaking have never been studied. Existing models for neuronal polarization disagree: some predict that neurons with more neurites polarize up to several days later than neurons with fewer neurites, while others predict that neurons with different neurite counts polarize synchronously. We experimentally find that neurons with different neurite counts polarize synchronously. We also show that despite the significant differences among the previously proposed models, they all agree with our experimental findings when the expression levels of the proteins responsible for symmetry breaking increase with neurite count. Consistent with these results, we observe that the expression levels of two of these proteins, HRas and shootin1, significantly correlate with neurite count. This coordinated symmetry breaking we observed among neurons with different neurite counts may be important for synchronized polarization of neurons in developing organisms