Outcome of atypical haemolytic uraemic syndrome relapse after eculizumab withdrawal

Background. The introduction of eculizumab has significantly improved the outcome of patients with atypical haemolytic uraemic syndrome (aHUS). Because of the risk of relapse after discontinuation, eculizumab was proposed as life-long therapy. However, data on the outcome of relapse are limited. In the Netherlands, patients with aHUS are treated with a restrictive eculizumab regime and are included in a national observational study (CUREiHUS, Dutch Trial Register NTR5988/NL5833). Methods. For this interim safety analysis, we evaluated the outcome of all adult patients with a suspected relapse, defined as the need to intensify eculizumab after tapering or withdrawal of therapy. Results. We describe 11 patients who received renewed eculizumab therapy because of suspected relapse. In three patients with aHUS in native kidneys, estimated glomerular filtration rate (eGFR) returned to baseline value and remained stable without overt proteinuria after follow-up. Six out of eight transplanted patients responded to eculizumab therapy with improvement in eGFR. After a median follow-up of 24.6 months, a reduction of eGFR >= 25% was observed in three of these transplanted patients, which was attributed to the aHUS relapse in only one patient. Conclusions. This interim analysis suggests that re-treatment with eculizumab after relapse is safe and feasible. We will continue to use our restrictive treatment strategy

Investigation of transition frequencies of two acoustically coupled bubbles using a direct numerical simulation technique

The theoretical results regarding the ``transition frequencies'' of two acoustically interacting bubbles have been verified numerically. The theory provided by Ida [Phys. Lett. A 297 (2002) 210] predicted the existence of three transition frequencies per bubble, each of which has the phase difference of $\pi /2$ between a bubble's pulsation and the external sound field, while previous theories predicted only two natural frequencies which cause such phase shifts. Namely, two of the three transition frequencies correspond to the natural frequencies, while the remaining does not. In a subsequent paper [M. Ida, Phys. Rev. E 67 (2003) 056617], it was shown theoretically that transition frequencies other than the natural frequencies may cause the sign reversal of the secondary Bjerknes force acting between pulsating bubbles. In the present study, we employ a direct numerical simulation technique that uses the compressible Navier-Stokes equations with a surface-tension term as the governing equations to investigate the transition frequencies of two coupled bubbles by observing their pulsation amplitudes and directions of translational motion, both of which change as the driving frequency changes. The numerical results reproduce the recent theoretical predictions, validating the existence of the transition frequencies not corresponding to the natural frequency.Comment: 18 pages, 8 figures, in pres

A regional benthic fauna assessment method for the Southern North Sea using Margalef diversity and reference value modelling

The aims of this study are to develop an optimized method for regional benthic fauna assessment of the Southern North Sea which (a) is sensitive and precise (quantified as the slope and the R2 value of the pressure-impact relationships, respectively) for the anthropogenic pressures bottom fishing and organic enrichment, (b) is suitable for estimating and modelling reference values, (c) is transparent, (d) can be efficiently applied using dedicated software; and to apply this method to benthic data from the Southern North Sea. Margalef diversity appeared to be the best performing benthic index regarding these criteria, even better than several Multi-Metric Indices (MMIs) containing e.g. AMBI (AZTI Marine Biotic Index) and ITI (Infaunal Trophic Index). Therefore, this relatively simple and very practical index, including a new reference value estimation and modelling method, and BENMMI software were selected as a common OSPAR (Oslo Paris convention) method for the benthic fauna assessment of the Southern North Sea. This method was applied to benthic fauna data from the Southern North Sea collected during the period 2010–2015. The results in general show lower normalized Margalef values in coastal areas, and higher normalized Margalef values in deeper offshore areas. The following benthic indices were compared in this study: species richness, Margalef diversity, SNA index, Shannon index, PIE index, AMBI, ITI. For each assessment area, the least disturbed benthic dataset was selected as an adjacent 6 year period with, on average, the highest Margalef diversity values. For these datasets, the reference values were primarily set as the 99th percentile values of the respective indices. This procedure results in the highest stable reference values that are not outliers. In addition, a variable percentile method was developed, in which the percentile value is adjusted to the average bottom fishing pressure (according to data from the International Council for the Exploration of the Sea, ICES) in the period 2009–2013. The adjusted percentile values were set by expert judgement, at 75th (low fishing pressure), 95th (medium fishing pressure) and 99th (high fishing pressure) percentile. The estimated reference values for Margalef diversity correlate quite well with the median depth of the assessment areas using a sigmoid model (pseudo-R2 = 0.86). This relationship between depth and Margalef diversity was used to estimate reference values in case an assessment area had insufficient benthic data .For testing the effects of bottom fishing pressure, normalized index values (NIV; index value divided by reference value) were used. The rationale for using NIVs is the assumption that, although a certain level of bottom fishing pressure will have a larger absolute effect on more biodiverse benthic communities in deeper waters than on more robust and less biodiverse coastal benthic communities, the relative effects (tested using NIVs) are comparable. A clear exponentially decreasing relationship (R2 = 0.26–0.27, p 2 cm, respectively) and normalized Margalef diversity values, with an asymptotic normalized Margalef value of 0.45 at a subsurface fishing activity >2.3 sweeps/year. This asymptotic value is predominantly found in coastal waters, and probably shows that the naturally more robust coastal benthic communities have been transformed into resilient benthic communities, which rapidly recover from increasing fishing pressure

Trends in biomass, density and diversity of North Sea macrofauna

Total biomass and biomass of large taxonomic groups (polychaetes, molluscs, crustaceans, echinoderms) and species diversity of the macrofauna were determined for almost 200 North Sea stations sampled synoptically by seven vessels during Spring 1986 and for 120 additional stations sampled in earlier years by the Marine Laboratory in Aberdeen. There exists a clear and significant decreasing trend in biomass with latitude, both in total biomass and for the different taxonomic groups. Apart from latitude, sediment composition and chlorophyll a content of the sediment also infuence total biomass and biomass of most groups significantly. Biomass increases consistently in finer sediments and sediments with a higher chlorophyll a content. The same trends are found for the results within laboratories. Some interaction exists, indicating weak laboratory and zonal effects. Diversity, as measured by Hill's diversity index N1 = (exp H′) shows a clear and significant trend with latitude. Towards the north of the North Sea diversity increases considerably. The trend is also found for laboratories separately and is everywhere equally strong. Also longitude and depth show an effect on diversity. Sediment variables have no clear influence on diversity. Other diversity measures show the same trend but are more variable than N1,. Total density tends to increase towards the north, but sediment related variables have a larger influence. Mean individual weight becomes considerably smaller towards the northern part of the North Sea

Long-term Observations Reveal Environmental Conditions and Food Supply Mechanisms at an Arctic Deep-Sea Sponge Ground

Deep-sea sponge grounds are hotspots of benthic biomass and diversity. To date, very limited data exist on the range of environmental conditions in areas containing deep-sea sponge grounds and which factors are driving their distribution and sustenance. We investigated oceanographic conditions at a deep-sea sponge ground located on an Arctic Mid-Ocean Ridge seamount. Hydrodynamic measurements were performed along Conductivity-Temperature-Depth transects, and a lander was deployed within the sponge ground that recorded near-bottom physical properties as well as vertical fluxes of organic matter over an annual cycle. The data demonstrate that the sponge ground is found at water temperatures of −0.5°C to 1°C and is situated at the interface between two water masses at only 0.7° equatorward of the turning point latitude of semi-diurnal lunar internal tides. Internal waves supported by vertical density stratification interact with the seamount topography and produce turbulent mixing as well as resuspension of organic matter with temporarily very high current speeds up to 0.72 m s−1. The vertical movement of the water column delivers food and nutrients from water layers above and below toward the sponge ground. Highest organic carbon flux was observed during the summer phytoplankton bloom period, providing fresh organic matter from the surface. The flux of fresh organic matter is unlikely to sustain the carbon demand of this ecosystem. Therefore, the availability of bacteria, nutrients, and dissolved and particulate matter, delivered by tidally forced internal wave turbulence and transport by horizontal mean flows, likely plays an important role in meeting ecosystem-level food requirements

Different Aspects of Classical Pathway Overactivation in Patients With C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis

The rare and heterogeneous kidney disorder C3 glomerulopathy (C3G) is characterized by dysregulation of the alternative pathway (AP) of the complement system. C3G is often associated with autoantibodies stabilizing the AP C3 convertase named C3 nephritic factors (C3NeF). The role of classical pathway (CP) convertase stabilization in C3G and related diseases such as immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) remains largely unknown. Here, we investigated the CP convertase activity in patients with C3G and IC-MPGN. Using a refined two-step hemolytic assay, we measured the stability of CP convertases directly in the serum of 52 patients and 17 healthy controls. In four patients, CP convertase activity was prolonged compared to healthy controls, i.e. the enzymatic complex was stabilized. In three patients (2 C3G, 1 IC-MPGN) the convertase stabilization was caused by immunoglobulins, indicating the presence of autoantibodies named C4 nephritic factors (C4NeFs). Importantly, the assay also enabled detection of non-immunoglobulin-mediated stabilization of the CP convertase in one patient with C3G. Prolonged CP convertase activity coincided with C3NeF activity in all patients and for up to 70 months of observation. Crucially, experiments with C3-depleted serum showed that C4NeFs stabilized the CP C3 convertase (C4bC2a), that does not contain C3NeF epitopes. All patients with prolonged CP convertase activity showed clear signs of complement activation, i.e. lowered C3 and C5 levels and elevated levels of C3d, C3bc, C3bBbP, and C5b-9. In conclusion, this work provides new insights into the diverse aspects and (non-)immunoglobulin nature of factors causing CP convertase overactivity in C3G/IC-MPGN.</p

The effect of local hydrodynamics on the spatial extent and morphology of cold-water coral habitats at Tisler Reef, Norway

This study demonstrates how cold-water coral morphology and habitat distribution are shaped by local hydrodynamics, using high-definition video from Tisler Reef, an inshore reef in Norway. A total of 334 video frames collected on the north-west (NW) and south-east (SE) side of the reef were investigated for Lophelia pertusa coral cover and morphology and for the cover of the associated sponges Mycale lingua and Geodia sp. Our results showed that the SE side was a better habitat for L. pertusa (including live and dead colonies). Low cover of Geodia sp. was found on both sides of Tisler Reef. In contrast, Mycale lingua had higher percentage cover, especially on the NW side of the reef. Bush-shaped colonies of L. pertusa with elongated branches were the most abundant coral morphology on Tisler Reef. The highest abundance and density of this morphology were found on the SE side of the reef, while a higher proportion of cauliflower-shaped corals with short branches were found on the NW side. The proportion of very small L. pertusa colonies was also significantly higher on the SE side of the reef. The patterns in coral spatial distribution and morphology were related to local hydrodynamics—there were more frequent periods of downwelling currents on the SE side—and to the availability of suitable settling substrates. These factors make the SE region of Tisler Reef more suitable for coral growth. Understanding the impact of local hydrodynamics on the spatial extent and morphology of coral, and their relation to associated organisms such as sponges, is key to understanding the past and future development of the reefVersión del editor3,87

Role of deep sponge grounds in the Mediterranean Sea: a case study in southern Italy

The Mediterranean spongofauna is relatively well-known for habitats shallower than 100 m, but, differently from oceanic basins, information upon diversity and functional role of sponge grounds inhabiting deep environments is much more fragmentary. Aims of this article are to characterize through ROV image analysis the population structure of the sponge assemblages found in two deep habitats of the Mediterranean Sea and to test their structuring role, mainly focusing on the demosponges Pachastrella monilifera Schmidt, 1868 and Poecillastra compressa (Bowerbank, 1866). In both study sites, the two target sponge species constitute a mixed assemblage. In the Amendolara Bank (Ionian Sea), where P. compressa is the most abundant species, sponges extend on a peculiar tabular bedrock between 120 and 180 m depth with an average total abundance of 7.3 +/- 1.1 specimens m(-2) (approximately 230 gWW m(-2) of biomass). In contrast, the deeper assemblage of Bari Canyon (average total abundance 10.0 +/- 0.7 specimens m(-2), approximately 315 gWW m(-2) of biomass), located in the southwestern Adriatic Sea between 380 and 500 m depth, is dominated by P. monilifera mixed with living colonies of the scleractinian Madrepora oculata Linnaeus, 1758, the latter showing a total biomass comparable to that of sponges (386 gWW m(-2)). Due to their erect growth habit, these sponges contribute to create complex three-dimensional habitats in otherwise homogenous environments exposed to high sedimentation rates and attract numerous species of mobile invertebrates (mainly echinoderms) and fish. Sponges themselves may represent a secondary substrate for a specialized associated fauna, such zoanthids. As demonstrated in oceanic environments sponge beds support also in the Mediterranean Sea locally rich biodiversity levels. Sponges emerge also as important elements of benthic-pelagic coupling in these deep habitats. In fact, while exploiting the suspended organic matter, about 20% of the Bari sponge assemblage is also severely affected by cidarid sea urchin grazing, responsible to cause visible damages to the sponge tissues (an average of 12.1 +/- 1.8 gWW of individual biomass removed by grazing). Hence, in deep-sea ecosystems, not only the coral habitats, but also the grounds of massive sponges represent important biodiversity reservoirs and contribute to the trophic recycling of organic matter

Meiofauna in the Gollum Channels and the Whittard Canyon, Celtic Margin—How Local Environmental Conditions Shape Nematode Structure and Function

The Gollum Channels and Whittard Canyon (NE Atlantic) are two areas that receive high input of organic matter and phytodetritus from euphotic layers, but they are typified by different trophic and hydrodynamic conditions. Sediment biogeochemistry was analysed in conjunction with structure and diversity of the nematode community and differences were tested between study areas, water depths (700 m vs 1000 m), stations, and sediment layers. The Gollum Channels and Whittard Canyon harboured high meiofauna abundances (1054–1426 ind. 10 cm−2) and high nematode diversity (total of 181 genera). Next to enhanced meiofauna abundance and nematode biomass, there were signs of high levels of organic matter deposition leading to reduced sedimentary conditions, which in turn structured the nematode community. Striking in this respect was the presence of large numbers of ‘chemosynthetic’ Astomonema nematodes (Astomonema southwardorum, Order Monhysterida, Family Siphonolaimidae). This genus lacks a mouth, buccal cavity and pharynx and possesses a rudimentary gut containing internal, symbiotic prokaryotes which have been recognised as sulphur-oxidising bacteria. Dominance of Astomonema may indicate the presence of reduced environments in the study areas, which is partially confirmed by the local biogeochemical environment. The nematode communities were mostly affected by sediment layer differences and concomitant trophic conditions rather than other spatial gradients related to study area, water depth or station differences, pointing to small-scale heterogeneity as the main source of variation in nematode structure and function. Furthermore, the positive relation between nematode standing stocks, and quantity and quality of the organic matter was stronger when hydrodynamic disturbance was greater. Analogically, this study also suggests that structural diversity can be positively correlated with trophic conditions and that this relation is tighter when hydrodynamic disturbance is greater