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Poroelastic fluid-structure interaction models were coupled to experimental data to determine the effects of biofilm spatial distribution of mechanical and hydraulic properties on the biofilm hydraulic resistance and compressibility in membrane filtration processes. Biofilms were cultivated on ultrafiltration membranes for 20 and 30 days under high (0.28 bar) and low (0.06 bar) transmembrane pressure (TMP), in dead-end filtration mode. Subsequently, biofilms were subjected to a compression/relaxation cycles by step-wise TMP changes. Structural deformation of biofilms during compression was observed in-situ using optical coherence tomography. Experimental results show that the observed increase in the biofilm hydraulic resistance during compression is not necessarily accompanied by a detectable biofilm thickness reduction. A dual-layer biofilm model with a dense base and porous top layer could explain these observed results. Because porosity controls indirectly the mechanical response of biofilms under compression, results could be described without assuming a gradient in mechanical properties within the biofilm. The biofilm surface roughness did not significantly influence the water flux in this study. However, the fraction of biofilm base layer directly exposed to bulk liquid could be a good indicator in the determination of water flux. The main implications of this study for the design and operation of low-pressure membrane systems (e.g., MF and UF with fouling layer being the main filtration resistance) lays in the selection of favorable operational TMP and biofilm morphology. • OCT images linked to poroelastic models explain biofilm deformation and water flux. • Increased hydraulic resistance was not accompanied by biofilm thickness reduction. • Biofilm porosity controls indirectly the biofilm mechanical response to compression. • Permeate flux through biofilm is dictated by a thin and dense base layer. • A novel flux indicator based on biofilm morphology was proposed. [ABSTRACT FROM AUTHOR]

Abstract Microbial biofilms can be both cause and cure to a range of emerging societal problems including antimicrobial tolerance, water sanitation, water scarcity and pollution. The identities of extracellular polymeric substances (EPS) responsible for the establishment and function of biofilms are poorly understood. The lack of information on the chemical and physical identities of EPS limits the potential to rationally engineer biofilm processes, and impedes progress within the water and wastewater sector towards a circular economy and resource recovery. Here, a multidisciplinary roadmap for addressing this EPS identity crisis is proposed. This involves improved EPS extraction and characterization methodologies, cross-referencing between model biofilms and full-scale biofilm systems, and functional description of isolated EPS with in situ techniques (e.g. microscopy) coupled with genomics, proteomics and glycomics. The current extraction and spectrophotometric characterization methods, often based on the principle not to compromise the integrity of the microbial cells, should be critically assessed, and more comprehensive methods for recovery and characterization of EPS need to be developed. Graphical abstract Image 1 Highlights • Extracellular polymeric substances feature in key societal problems (clinical, environmental). • Methods and standards of EPS recovery and characterization need to be critically assessed. • More emphasis should be placed on methods that enable identification (chemical and function). • Integrated and multi-displinary analyses are required on biofilms and EPS isolates. • Will improve biofilm management and enable a more circular economy in water and waste. [ABSTRACT FROM AUTHOR]

• A new mechanistic 1D biofilm model introduces a distinction between PN and PS. • A volume detachment process that depends on the physical properties is considered. • The stratification of physical properties and biofilm composition is captured. • The influence of COD/N, shear stress and SOLR on EPS composition is considered. • The model captures qualitatively the influence of these growth conditions. In industry, treatments against biofilms need to be optimized and, in the wastewater treatment field, biofilm composition needs to be controlled. Therefore, describing the biochemical and physical structures of biofilms is now required to better understand the influence of operating parameters and treatment on biofilms. The present study aims to investigate how growth conditions influence EPS composition, biofilm physical properties and volume detachment using a 1D biofilm model. Two types of EPS are considered in the present model, proteins and polysaccharides. The main hypotheses are that: (i) the production of polysaccharides occurs mainly under strong nutrient limitation(s) while the production of proteins is coupled to both the substrate uptake rate and the lysis process; (ii) the local biofilm porosity depends on the local biofilm composition. Both volume and surface detachment occur in biofilms and volume detachment extent depends on the biofilm local cohesion and thus on the local composition of biofilms for a given shear stress. The model is based on experimental trends and aims to represent these observations on the basis of biochemical and physical processes. Four case studies covering a wide range of contrasting growth conditions such as different COD/N ratios, applied SOLR and shear stresses are investigated. The model predicts how the biochemical and physical biofilm structures change as a result of contrasting growth conditions. More precisely simulation results are in good agreement with the main experimental observations reported in the literature, such as: (i) a strong nitrogen limitation of growth induces an important accumulation of polysaccharides leading to a more porous and homogenous biofilm, (ii) a high applied surface organic loading load allows to obtain a high biofilm thickness, (iii) a strong shear stress applied during the biofilm growth leads to a reduction of the biofilm thickness and to a consolidation of the biofilm structure. Overall, this model represents a relevant decision tool for the selection of appropriate enzymatic treatments in the context of negative biofilm control. From our results, it appears that protease based treatments should be more appropriate for biofilms developed under low COD/N ratios (about 20 gCOD/gN) whereas both glucosidases and proteases based treatments should be more appropriate for biofilms developed under high COD/N ratio (about 70 gCOD/gN). In addition, the model could be useful for other applications such as resource recovery in biofilms or granules, and help to better understand biological membrane fouling. [ABSTRACT FROM AUTHOR]

To this day, obtaining reliable characterization of sludge settling properties remains a challenging and time-consuming task. Without such assessments however, optimal design and operation of secondary settling tanks is challenging and conservative approaches will remain necessary. With this study, we show that automated sludge blanket height registration and zone settling velocity estimation is possible thanks to analysis of images taken during batch settling experiments. The experimental setup is particularly interesting for practical applications as it consists of off-the-shelf components only, no moving parts are required, and the software is released publicly. Furthermore, the proposed multivariate shape constrained spline model for image analysis appears to be a promising method for reliable sludge blanket height profile registration. [ABSTRACT FROM AUTHOR]

This study aimed at evaluating the formation of aerobic granular sludge (AGS) for the treatment of real and low-strength municipal wastewater using a column sequencing batch reactor (SBR) operated in fill-draw mode (constant volume). The focus was on understanding how the wastewater upflow velocity (V WW ) applied during the anaerobic feeding influenced the sludge properties and in turn the substrate conversion. Two different strategies were tested: (1) washing-out the flocs by imposing high wastewater upflow velocities (between 5.9 and 16 m h −1 ) during the anaerobic feeding (Approach #1) and (2) selective utilization of organic carbon during the anaerobic feeding (1 m h −1 ) combined with a selective sludge withdrawal (Approach #2). A column SBR of 190 L was operated in constant volume during 1500 days and fed with real and low-strength municipal wastewater. The formation of AGS with SVI 30 of around 80 mL g TSS −1 was observed either at very low (1 m h −1 ) or at high V WW (16 m h −1 ). At 16 m h −1 the AGS was mainly composed of large and round granules (d > 0.63 mm) with a fluffy surface, while at 1 m h −1 the sludge was dominated by small granules (0.25 < d < 0.63 mm). The AGS contained a significant fraction of flocs during the whole operational period. A considerable and continuous washout of biomass occurred at V WW higher than 5.9 m h −1 (Approach #1) due to the lower settling velocity of the AGS fed with municipal wastewater. The low sludge retention observed at V WW higher than 5.9 m h −1 deteriorated the substrate conversion and in turn the effluent quality. High solid concentrations (and thus solid retention time) were maintained during Approach #2 (V WW of 1 m h −1 ), which resulted in an excellent effluent quality. The study demonstrated that the formation of AGS is possible during the treatment of real and low-strength municipal wastewater in a SBR operated at constant volume. Low wastewater upflow velocities should be applied during the anaerobic feeding phase in order to ensure enough biomass retention and efficient substrate removal. [ABSTRACT FROM AUTHOR]

This study aimed at identifying how to improve the level of permeate flux stabilisation during gravity-driven membrane filtration without control of biofilm formation. The focus was therefore on understanding (i) how the different fractions of the biofilms (inorganics particles, bacterial cells, EPS matrix) influence its hydraulic resistance and (ii) how the compression of biofilms impacts its hydraulic resistance, i.e., can water head be increased to increase the level of permeate flux stabilisation. Biofilms were developed on ultrafiltration membranes at 88 and 284 cm water heads with dead-end filtration for around 50 days. A larger water head resulted in a smaller biofilm permeability (150 and 50 L m −2 h −1 bar −1 for biofilms grown at 88 cm and 284 cm water head, respectively). Biofilms were mainly composed of EPS (>90% in volume). The comparison of the hydraulic resistances of biofilms to model fouling layers indicated that most of the hydraulic resistance is due to the EPS matrix. The compressibility of the biofilm was also evaluated by subjecting the biofilms to short-term (few minutes) and long-term variations of transmembrane pressures (TMP). A sudden change of TMP resulted in an instantaneous and reversible change of biofilm hydraulic resistance. A long-term change of TMP induced a slow change in the biofilm hydraulic resistance. Our results demonstrate that the response of biofilms to a TMP change has two components: an immediate variation of resistance (due to compression/relaxation) and a long-term response (linked to biofilm adaptation/growth). Our results provide relevant information about the relationship between the operating conditions in terms of TMP, the biofilm structure and composition and the resulting biofilm hydraulic resistance. These findings have practical implications for a broad range of membrane systems. [ABSTRACT FROM AUTHOR]

Résumé La mise sur le marché de nouveaux anticoagulants oraux (NACO) soulève la question de la prise en charge des hémorragies intracrâniennes survenant lors d’un traitement par ces molécules. Le dabigatran, le rivaroxaban et l’apixaban présentent des caractéristiques pharmacologiques différentes que les praticiens doivent connaître pour adapter leur prescription au patient. Les études d’efficacité et de sécurité ayant précédé la commercialisation de ces molécules ont mis en évidence une diminution du risque d’hémorragie intracrânienne par rapport aux antivitamines K. Néanmoins, aucune donnée fiable n’est disponible quant au pronostic de ces hémorragies survenues sous NACO. De plus, l’absence d’antidote spécifique et de protocole de réversion validé chez l’Homme place l’anesthésiste-réanimateur dans une situation délicate en cas d’hémorragie critique. La rapidité du rétablissement des capacités hémostatiques est alors un facteur déterminant du pronostic. Des études animales ou sur volontaires sains ont montré une correction des paramètres biologiques par les concentrés de complexes prothrombiniques activés ou non, sans diminution du volume de saignement constaté. Sur ces bases, des propositions ont été émises par le groupe d’intérêt en hémostase peropératoire pour la prise en charge des hémorragies sous NACO, dont une partie est consacrée à la prise en charge du saignement cérébral. The recent release of new oral anticoagulants (NOAC) raises the question of the management of intracranial hemorrhage occurring during treatment with these molecules. Dabigatran, rivaroxaban and apixaban have different pharmacological characteristics that physicians need to know to adjust their prescription to each patient. Studies of efficacy and safety prior to the marketing of these molecules showed a decreased risk of intracranial hemorrhage compared with vitamin K antagonists. However, no reliable data are available regarding the prognosis of these hemorrhages occurring during NOAC treatment. In addition, there is no specific antidote and reversal protocol validated in humans. So, physicians are in a difficult situation when critical bleeding occurs. The timing of recovering normal hemostatic capacity is then a determinant factor of prognosis. Studies in animals or healthy volunteers showed a correction of the biological parameters using prothrombin complex concentrates activated or not, without reducing the volume of hematoma. On this basis, proposals have been issued by the french group of interest for perioperative hemostasis (GIHP) for the management of bleeding under NOAC treatment, which include management of intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluates the effect of the presence of biofilms on membrane surfaces on the quality of permeate produced during Gravity-driven membrane ultrafiltration. GDM ultrafiltration is applied to the decentralized production of drinking water. A second objective was to evaluate to what extent permeate quality is enhanced by pre-treating feed-water (using a packed bed biofilm reactor or a slow sand filter). The influence of the ageing of the biofilm on the permeate quality was evaluated and compared to the effect of virgin membranes. Permeate quality was evaluated in terms of Assimilable Organic Carbon (AOC) content and dissolved organic carbon fractions (e.g. biopolymers). Our results indicate that virgin ultrafiltration membrane remove a small fraction of the AOC and biopolymers (rejection <10%). The presence of a young and thin biofilm on the surface of the ultrafiltration membranes increases the permeate quality due to the degradation of AOC (>80%). However, over long-term the hydrolysis of the organic matter that accumulated on membrane surfaces increases the AOC content of the permeate, thus deteriorating the permeate quality. Pre-treatment of the feed-water help to control the biofilm accumulation and thus to limit the deterioration of the permeate quality. Permeate flux stabilised at average values of 7.5–8.9 L m−2 h−1. But the presence of pre-treatment helped to increase permeate flux (+12 and 19%, with the packed bed biofilm reactor and with the slow sand filter, respectively). Overall our study demonstrates that tolerating the presence of biofilm on membrane surface has a beneficial effect on the quality of permeate even if its quantity is decreased. [Copyright &y& Elsevier]

Abstract: Wastewater pH affects the transfer of H2S from liquid to gas and hence impacts on the extent of odour and corrosion. Sewage pH may change significantly in sewer networks due to, for example, the fermentation of organic compounds, particularly when the hydraulic retention time is long, the discharge of trade wastes that are organic-rich or with extreme pH, and the intentional addition of alkali to raise the sewage pH. Such a variation of pH is expected to affect sulfate reduction by sewer biofilms. In this work, experimental studies were carried out to reveal the detailed effects of pH on sulfidogenesis by anaerobic sewer biofilms developed in a laboratory sewer reactor fed with real sewage, and the potential causes for the inhibitory effects observed under both high and low pH conditions. The data clearly showed that the sewer biofilm had the highest sulfate reduction rate at around neutral pH (6.5–7.5), and the activity decreased when pH was higher or lower. The data also suggested that the inhibiting effect at a higher pH is likely due to the inhibitory effects of free ammonia, while at a lower pH it is more likely due to the pH itself. An inhibition model formulated based on the above hypotheses was able to adequately describe the measured sulfide production rates under different pH levels and different free ammonia concentrations, as well as data previously reported in literature. The calibrated model was used to simulate sulfide production in a sewer network receiving alkali dosage. The model adequately predicted sulfide production in the network, which could not be achieved with a model not considering the pH effect. [Copyright &y& Elsevier]

Abstract: The impact of different feed waters in terms of eukaryotic populations and organic carbon content on the biofilm structure formation and permeate flux during Gravity-Driven Membrane (GDM) filtration was investigated in this study. GDM filtration was performed at ultra-low pressure (65 mbar) in dead-end mode without control of the biofilm formation. Different feed waters were tested (River water, pre-treated river water, lake water, and tap water) and varied with regard to their organic substrate content and their predator community. River water was manipulated either by chemically inhibiting all eukaryotes or by filtering out macrozoobenthos (metazoan organisms). The structure of the biofilm was characterized at the meso- and micro-scale using Optical Coherence Tomography (OCT) and Confocal Laser Scanning Microscopy (CLSM), respectively. Based on Total Organic Carbon (TOC) measurements, the river waters provided the highest potential for bacterial growth whereas tap water had the lowest. An increasing content in soluble and particulate organic substrate resulted in increasing biofilm accumulation on membrane surface. However, enhanced biofilm accumulation did not result in lower flux values and permeate flux was mainly influenced by the structure of the biofilm. Metazoan organisms (in particular nematodes and oligochaetes) built-up protective habitats, which resulted in the formation of open and spatially heterogeneous biofilms composed of biomass patches. In the absence of predation by metazoan organisms, a flat and compact biofilm developed. It is concluded that the activity of metazoan organisms in natural river water and its impact on biofilm structure balances the detrimental effect of a high biofilm accumulation, thus allowing for a broader application of GDM filtration. Finally, our results suggest that for surface waters with high particulate organic carbon (POC) content, the use of worms is suitable to enhance POC removal before ultrafiltration units. [Copyright &y& Elsevier]

Abstract: This study aims at evaluating the mechanisms of biofilm detachment with regard of the physical properties of the biofilm. Biofilms were developed in Couette–Taylor reactor under controlled hydrodynamic conditions and under different environmental growth conditions. Five different conditions were tested and lead to the formation of two aerobic heterotrophic biofilms (aeHB1 and aeHB2), a mixed autotrophic and heterotrophic biofilm (MAHB) and two anoxic heterotrophic biofilms (anHB1 and anHB2). Biofilm detachment was evaluated by monitoring the size of the detached particles (using light-scattering) as well as the biofilm physical properties (using CCD camera and image analysis). Results indicate that volume erosion of large biofilm particles with size ranging from 50 to 500μm dominated the biomass loss for all biofilms. Surface erosion of small particles with size lower than 20μm dominates biofilm detachment in number. The extent of the volume detachment events was governed by the size of the biofilm surface heterogeneities (i.e., the absolute biofilm roughness) but never impacted more than 80% of the mean biofilm thickness due to the highly cohesive basal layer. Anoxic biofilms were smoother and thinner than aerobic biofilms and thus associated with the detachment of smaller particles. Our results contradict the simplifying assumption of surface detachment that is considered in many biofilm models and suggest that discrete volume events should be considered. [Copyright &y& Elsevier]

Abstract: Introduction: Evidence shows that smoking leads to more perioperative complications. Smoking cessation before surgery reduces this postoperative morbidity. The French Society of Anaesthesia and Intensive Care published recommendations on this subject in 2005. We wanted to assess knowledge and practice amongst anaesthetists in Lorraine as regards the management of smoking in the perioperative period. Methods: We conducted an internet-based survey of 365 anaesthetists in the Lorraine region during November and December 2011. At the same time, we also surveyed patients attending pre-assessment clinic at the CHU hospital, Nancy. Results: Half the practitioners surveyed were aware of the 2005 guidelines. Most pre-assessment clinics do not display posters warning of the perioperative hazards of smoking. The need for smoking cessation advice as a bare minimum is acknowledged by 47.9% of experienced practitioners; 76.3% of anaesthetists claim to offer advice occasionally, frequently or systematically. On the other hand, only 17% of the patients surveyed report receiving such advice. Conclusion: Despite published guidelines on the benefits of smoking cessation prior to surgery, Lorraine anaesthetists fail to systematically advise their patients in this regard. We believe there is a need to improve the management of these patients, either through the development of smoking cessation protocols locally or through patient referral to a specialised clinic. [Copyright &y& Elsevier]

Abstract: This study investigates the impact of predation by eukaryotes on the development of specific biofilm structures in gravity-driven dead-end ultrafiltration systems. Filtration systems were operated under ultra-low pressure conditions (65 mbar) without the control of biofilm formation. Three different levels of predation were evaluated: (1) inhibition of eukaryotic organisms, (2) addition of cultured protozoa (Tetrahymena pyriformis), and (3) no modification of microbial community as a control. The system performance was evaluated based on permeate flux and structures of the biofilm. It was found that predation had a significant influence on both the total amount and also the structure of the biofilm. An open and heterogeneous structure developed in systems with predation whereas a flat, compact, and thick structure that homogeneously covered the membrane surface developed in absence of predation. Permeate flux was correlated with the structure of the biofilm with increased fluxes for smaller membrane coverage. Permeate fluxes in the presence or absence of the predators was 10 and 5 L m−2 h−1, respectively. It was concluded that eukaryotic predation is a key factor influencing the performance of gravity-driven ultrafiltration systems. [Copyright &y& Elsevier]

A recent study showed that, in addition to precipitating sulfides, Fe3+ addition to sewers reduces the sulfate-reducing and methanogenic activities of anaerobic sewer biofilms. The dynamic response of these activities to the commencement and termination of ferric dosage is investigated in this study. Both the sulfate-reduction and methane-production rates of anaerobic sewer biofilms decreased upon the addition of ferric ions, with a maximum inhibition of approximately 50% achieved after 3 and 7 days, respectively. In comparison, the sulfate-reducing activity of suspended biomass in the Fe3+ receiving reactor was completely inhibited. The volatile solids-to-total solids (VS/TS) ratio of sewer biofilms decreased from 91±3% before Fe3+ addition to 54±6% after a full adaptation of the biofilms to Fe3+ addition. Energy-dispersive spectroscopy profiles showed higher iron and sulfur contents in biofilms adapted to Fe3+ addition, suggesting FeS deposition in biofilms. We hypothesize that FeS precipitation primarily occurred in the upper layer of sewer biofilms causing inhibition to sulfate-reducing bacteria (SRB) and methanogenic archaea (MA) in this layer (and in the suspended phase). However, SRB and MA were likely to be active in the deep layer. The sulfate-reducing activity recovered to approximately 90% that of the reference reactor in 5 weeks after Fe3+ injection was stopped, whereas there was no recovery of the methanogenic activity in the same period. The results suggest that a temporary suspension of ferric dosage would not lead to immediate recovery of the sulfate-reducing and methanogenic activities. The recovery of sulfate-reducing activity was found to be linearly correlated with the recovery of biofilm VS/TS ratio, following the termination of Fe3+ addition. [ABSTRACT FROM AUTHOR]

Efficient nitrogen removal from wastewater containing high concentrations of ammonium but little organic substrate has recently been demonstrated by several full-scale applications of the combined nitritation-anammox process. While the process efficiency is in most cases very good, process instabilities have been observed to result in temporary process failures. In the current study, conditions resulting in instability and strategies to regain efficient operation were evaluated. First, data from full-scale operation is presented, showing a sudden partial loss of activity followed by recovery within less than 1 month. Results from laboratory-scale experiments indicate that these dynamics observed in full scale can be caused by partial inhibition of the ammonia oxidizing bacteria (AOB), while anammox inhibition is a secondary effect due to temporarily reduced O2 depletion. Complete anammox inhibition is observed at 0.2 mg O2∙L-1, resulting in NO2- accumulation. However, this inhibition of anammox is reversible within minutes after O2 depletion. Thus, variable AOB activity was identified as the key to reactor stability. With appropriate interpretation of the online NH4+ signal, accumulation of NO2- can be detected indirectly and used to signal an imbalance of O2 supply and AOB activity (no suitable online NO2- electrode is currently available). Second, increased abundance of nitrite-oxidizing bacteria (NOB; competing with anammox for NO2-) is known as another cause of instability. Based on a comparison of parallel full-scale reactors, it is suggested that an infrequent and short-term increased O2 supply (e.g., for maintenance of aerators) that exceeds prompt depletion of oxygen by AOB may have caused increased NOB abundance. The volumetric air supply as a proxy for O2 supply thus needs to be linked to AOB activity. Further, NOB can be washed out of the system during regular operation if the system is operated at a sludge age in the range of 45 days and by controlling the air supply according to the NO3- concentration in the treated effluent. Early detection of growing NOB abundance while the population is still low can help guide process operation and it is suggested that molecular methods of quantifying NOB abundance should be tested. [ABSTRACT FROM AUTHOR]

Gell's Art and Agency that aimed to articulate the first anthropological theory of art has achieved a near-cult status among the academic community. Departing from previous semiological and aesthetic approaches, this theory takes it that art is a form of instrumental action, the canonical efficacy of which lies in its power to function as a cognitive trap and to captivate the spectator's mind. In this article it is argued that Gell's theory is not as novel as it is claimed; that it fails to define the specific field of art; and that by excluding the aesthetic properties of art objects, it discards ethnographical data nonetheless necessary for understanding the agency of art in Melanesian local cultures. At a meta-level, Gell assigned to his theory the same captivating purpose as he did to art, and this probably explains the seductive fascination that his work continues to exert. [ABSTRACT FROM AUTHOR]

We evaluated how intermittent shear influences the physical structure, material properties and hydraulic resistance of membrane biofilms developed during gravity-driven ultrafiltration of river water, with the ultimate goal of increasing the filtration performances. Our results indicate intermittent shear helps slowing-down the flux decline but does not help to increase the level of stabilisation of the permeate flux. After several weeks, the biofilms exposed to different shear regimes were indeed characterised by similar hydraulic resistance. But the characteristic time to achieve a stable flux increased from 7 d to 25d when increasing the shear frequency. Also, most of the hydraulic resistance (up to 95%) was governed by the base layer that remained attached after erosion tests. With increasing exposure to shear conditions, the biofilms became more cohesive and more elastic, thus resisting better to cross flow conditions. Overall, our results demonstrate that engineering membrane biofilms with a desired permeability is not feasible using intermittent shear due to significant adaptability of the biofilms to their hydraulic environment. [Display omitted] • Effect of intermittent shear on the permeability of membrane biofilms was studied. • Intermittent shear conditions increase cohesiveness of the membrane biofilms. • Membrane biofilms with increased cohesiveness are less permeable. • Intermittent shear is not relevant to increase filtration flux during GDM filtration. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to use indirect methods to assess the biofilm cohesion and its vertical stratification. Biofilms were grown under low hydrodynamic strengths in two reactors, a low shear stress reactor (LSSR) or under a defined shear stress in a Couette-Taylor Reactor (CTR), using different electron donors and acceptors. The stratification of biofilm cohesion was characterized from a gradual increase of the hydrodynamic strengths in terms of shear stress (erosion) and abrasion (collisions of particles). Whatever the nature of the biofilms, erosion tests demonstrated a gradual impact of a wall shear stress increase on the biofilms remaining on the substratum surface. These observations demonstrated that the biofilm cohesion was heterogeneous and increased with the biofilm depth. Both erosion and abrasion tests highlighted a basal zone of high cohesion. Investigations based on PCR-SCCP and oxygen uptake rate showed the presence of active microorganisms in this zone. [Copyright &y& Elsevier]

This work deals with the cohesion and detachment in biofilm systems for two electron acceptors and for two electron donors. Biofilms were developed on plates, under very low shear stress for one month and then subjected to an erosion test for two hours in a Couette-Taylor reactor. Biofilm was characterised in terms of average thickness and residual TOC mass. It was found that the biofilm structure is very heterogeneous and stratified. The top layer, which represents 60% of the biofilm mass, is very fragile and can be easily detached; the basal layer, which represents 20% of the biofilm mass, is very cohesive and can resist shear stresses up to 13 Pa. Between these two layers, a middle layer of intermediary cohesion represents 20% of the initial biofilm mass. [ABSTRACT FROM AUTHOR]

Abstract. Several studies have shown that the prognosis of oligodendrogliomas is dependent on their histological grade. In order to identify a non-invasive method for the primary diagnosis and follow-up of these tumours, we investigated the relationship between their in vivo metabolism, assessed by positron emission tomography (PET), and their histological grade assessed at the same time. Forty-seven patients with histologically confirmed oligodendrogliomas were investigated. Conventional neuroradiological assessment by computed tomography and magnetic resonance imaging (MRI) was performed in all the patients. All the histology slices were reviewed by the same pathologist after referral from various pathology laboratories. The PET investigation included a carbon-1l methionine ([sup 11]C-MET) uptake study and, in the majority of cases, a fluorine-18 fluorodeoxyglucose ([sup 18]F-FDG) uptake study, in order to investigate at the same time both amino acid metabolism and glycolysis. The sampled tumour region of interest (ROI) was defined from the Tl-weighted 3D MR scan matched with the PET scan. Tracer concentration in each voxel of the tumour ROI was divided by the mean concentration in an ROI of the same size located in the healthy brain tissue. For each tumour and each tracer, we characterized the metabolic pattern on the basis of the mean and the maximum turnout to healthy tissue concentration ratio, and also the standard deviation and range of the ratios, which indicate the degree of metabolic heterogeneity of the tumour... [ABSTRACT FROM AUTHOR]

Résumé Le drug reaction with eosiniphilia and systemic symptoms (DRESS) est une réaction adverse médicamenteuse pouvant mettre en jeu le pronostic vital du patient. Les signes cliniques sont polymorphes et les atteintes viscérales variées. De plus, son délai d’apparition est long après la prise médicamenteuse responsable ; le diagnostic est donc particulièrement difficile en réanimation. Nous rapportons le cas d’une patiente atteinte de DRESS dans les suites opératoires d’une chirurgie intracrânienne compliquée d’une infection nosocomiale. Drug reaction with eosinophilia ans systemic symptoms (DRESS) is a severe medication-induced adverse reaction, which can threaten patient's life. Clinical symptoms and organ failures present wide variability. Furthermore, the latency period is long, so that diagnosis could be a real challenge in the intensive care unit. We report the case of a woman developing a DRESS after neurosurgery complicated by a nosocomial infection. [ABSTRACT FROM AUTHOR]

Increasing transmembrane pressure (TMP) can compress and increase the hydraulic resistance of membrane biofilms. The purpose of the present study is to evaluate how compression of membrane biofilms occurs and how structural rearrangement can affect hydraulic resistance. Biofilms with heterogeneous and homogeneous physical structures were grown in membrane fouling simulators (MFS) in dead-end mode for 20 days with either (i) a nutrient enriched condition with a nutrient ratio of 100:30:10 (C: N: P), (ii) a phosphorus limitation (C: N: P ratio: 100:30:0), or (iii) river water (C: N: P ratio: ca. 100:10:1). The structural and hydraulic response of membrane biofilms to (a) changes in transmembrane pressures ( 0.06-0.1-0.5-0.1-0. 06 bar) and (b) changes in permeate flux ( 10-15-20-15- 10 L/m 2 /h) were investigated. Optical coherence tomography (OCT) was used to monitor biofilm structural response, and OCT images were processed to quantify changes in the mean biofilm thickness and relative roughness. Nutrient enriched and river water biofilms had heterogeneous physical structures with greater surface roughness (Ra' > 0.2) than homogeneous P limiting biofilms (Ra' < 0.2). Compression of biofilms with rough heterogeneous structures (Ra' > 0.2) was irreversible, indicated by irreversible decrease in surface roughness, partial relaxation in mean biofilm thickness and irreversible increase in hydraulic resistance. Compression of homogeneous biofilm (Ra' < 0.2) was on the other hand reversible, indicated by full relaxation of the biofilms structure and restoration of initial hydraulic resistance. Hydraulic response (i.e., change in the specific biofilm resistance) did not correspond with the change in physical structure of heterogeneous biofilms. The presented study provides a fundamental understanding of how biofilm physical structure can affect the biofilm's response to a change in TMP, with practical relevance for the operation of GDM filtration systems. [ABSTRACT FROM AUTHOR]

Introduction Les deux principales complications du traitement endovasculaire des anévrysmes intra crâniens sont thromboemboliques et hémorragiques. La fréquence de survenue d’une complication thromboembolique est plus importante en cas d’hémorragie sous arachnoïdienne (HSA). Cette complication est prévenue par l’administration d’héparine non fractionnée (HNF). Les recommandations internationales proposent d’injecter un bolus de 50 à 100 UI/kg d’HNF, mais cette posologie est peu validée. L’objectif de ce travail était d’évaluer un nouveau protocole d’administration de l’HNF monitorée par l’ACT dans la prise en charge endovasculaire des anévrysmes intra crânien rompus. Matériel et méthodes Vingt patients traités par technique endovasculaire pour HSA anévrysmale ont été inclus prospectivement. Ils étaient anticoagulés par l’injection d’un bolus d’HNF (70 UI/kg) suivie d’une perfusion continue d’HNF (18 UI/kg/h). La cible d’ACT était comprise entre 250 et 300 s. Ils ont été comparés à un groupe historique de 100 patients traités pour HSA de façon similaire, anticoagulés avec un bolus d’HNF (50 UI/Kg) suivi d’une perfusion continue d’HNF (25 UI/kg/h), sans monitorage. Résultats Les valeurs initiales d’ACT étaient de 117 ± 8 s. Après l’administration d’un bolus d’HNF de 67,3 UI/kg (IQR 70,4–61,5), l’ACT mesuré était de 225 ± 85s. La perfusion continue d’HNF dans le groupe ACT était de 17,9 UI/kg/h (IQR 19,8–16,5). Elle était significativement plus faible que dans le groupe non monitoré (26,8 UI/kg/h [IQR 30,7–19,9]) ( p < 0,0001). L’ACT de contrôle, 30 min après le bolus, était de 182 ± 42s. Le bolus d’HNF, et la quantité totale d’HNF administrée étaient significativement plus élevés dans le groupe ACT : 67,3 UI/kg (IQR 70,4–61,5) versus 38,8 UI/kg (IQR 43,3–32,4), ( p < 0,0001), et 68,5 UI/kg/h (IQR 87,4–54,4) versus 54,8 UI/kg/h (IQR 68,8–45,5) ( p = 0,029). Le taux de complication était similaire dans les 2 groupes : complication thromboembolique 10 % versus 10 % ( p = 1) ; complication hémorragique 9 % versus 5 % (groupe ACT) ( p = 1) ( Fig. 1 ). Discussion Ce travail montre que l’administration d’un bolus d’HNF de 70 UI/kg suivi d’une perfusion continue d’HNF de 18 UI/kg/h ne permet pas d’atteindre l’objectif d’ACT (250–300s). L’hypercoagulabilité induite par l’HSA peut partiellement expliquer cette résistance à l’HNF. Les doses d’HNF doivent probablement être augmentées dans la prise en charge endovasculaire des anévrysmes intra crâniens rompus. [ABSTRACT FROM AUTHOR]

Carbon emission is calculated based on total activity data ( I AD i , expressed in units presented in Table 2) multiplied by the corresponding emission factors ( I EF i s), leading to a GHG emission output, expressed in gram (g), kilogram (kg), or metric tonne (t) of CO SB 2 sb equivalent (CO SB 2 sb e). A carbon footprint is defined by the Carbon Trust as "the total set of GHG emissions caused directly and indirectly by an individual, event, organization or product, expressed as carbon dioxide equivalent (CO SB 2 sb e)" [5]. Medical gas emissions (related to release of carbon dioxide) accounted for 11 kg CO SB 2 sb e. Discussion This is the first study to estimate the carbon footprint of GIE based on a multi-criteria analysis. Method of carbon footprint calculation The Bilan Carbone method evaluates direct GHG emissions resulting from activities that an organization controls (scope 1), emissions from energy use (scope 2), and indirect emissions from products and services an organization does not directly control (scope 3; Fig. [Extracted from the article]

Introduction Haemophilia is a major bleeding disorder due to a deficiency of procoagulant factor VIII (type A) or IX (type B). The treatment is substitutive and based on infusion of factor concentrates. Main limitations of this therapy are cost, short factor half-life and the development of inhibitors (up to 30% of severe HA patients). An important aggravating factor of haemophilia is due to a premature fibrinolysis, directing attention to the therapeutic potential of suitable antifibrinolytics. Thrombomodulin ( TM) is a key player of the coagulation cascade by activating protein C (an inhibitor of thrombin generation, thus antagonizing coagulation) and of the fibrinolytic cascade by activating thrombin activatable fibrinolysis inhibitor TAFI (thus reducing fibrinolysis). Solulin is a soluble form of TM that shows both capabilities. Aim Here, we developed a new generation of solulin variants (F376A-, M388A- and F376A/M388A-solulin) with a decreased ability to activate protein C and a conserved capacity to activate TAFI. Methods We produced and characterized solulin variants in vitro. In addition, F376A/M388A-solulin was tested ex vivo, using blood samples of haemophilic A patients, with thromboelastography. Results The solulin variants (F376A, M388A and the double-mutant F376A/M388A) lost their abilities to activate protein C but are still capable to activate TAFI. Thrombelastography showed increased clot firmness and stability, that, as opposed to wild-type solulin, was maintained even at high concentrations of F376A/M388A-solulin (100 n m). Conclusion In sum, these results open new opportunities for the development of specific medication for haemophilic patients. [ABSTRACT FROM AUTHOR]

• Biological selection alternates substrate feast and famine and controls SRT. • Carbon-storing heterotrophic bacteria help forming biological aggregates. • Selective biomass wasting with physical selection retains biological aggregates. • Biological selection and selective biomass wasting results in hybrid processes. • Mobile biofilms and aerobic granules can be utilized for WWT and BNR. There have been significant advances in the use of biological and physical selectors for the intensification of continuously flowing biological wastewater treatment (WWT) processes. Biological selection allows for the development of large biological aggregates (e.g., mobile biofilm, aerobic granules, and densified biological flocs). Physical selection controls the solids residence times of large biological aggregates and ordinary biological flocs, and is usually accomplished using screens or hydrocyclones. Large biological aggregates can facilitate different biological transformations in a single reactor and enhance liquid and solids separation. Continuous-flow WWT processes incorporating biological and physical selectors offer benefits that can include reduced footprint, lower costs, and improved WWT process performance. Thus, it is expected that both interest in and application of these processes will increase significantly in the future. This review provides a comprehensive summary of biological and physical selectors and their design and operation. [ABSTRACT FROM AUTHOR]

One strategy for the management of excess sludge in small wastewater treatment plants (WWTPs) consists in minimizing the excess sludge production by operating the WWTP at very long solids retention times (SRTs > 30 days). A number of recent studies have suggested that sludge minimization at very long SRT results from the degradation of the unbiodegradable particulate fraction (X U ) (influent unbiodegradable compounds and endogenous decay products). But the biodegradability of the unbiodegradable particulate fraction has only been evaluated during batch digestion test performed at ambient temperature with sludge fed with synthetic wastewaters. It is not clear to what extent observations made for sludge fed with synthetic influents can be transposed to sludge fed with real influent. The current study thus focused on evaluating the biodegradability of the unbiodegradable particulate fraction for sludge fed with real wastewater. Batch digestion tests (400 days, ambient temperature) were conducted with three different sludges fed with either synthetic or real influents and exposed to aerobic or intermittent aeration conditions. Our results indicate that volatile suspended solids (VSS) decreased even after complete decay of the active biomass (i.e., after 30 days of aerobic batch digestion) indicating that the unbiodegradable particulate fraction is biodegradable. However, very low degradation rates of the unbiodegradable particulate fraction were monitored after day 30 of digestion (0.7–1.7·10 −3 d −1 ). These values were in the lower range of previously published values for synthetic wastewaters (1–7.5·10 −3 d −1 ). The low values determined in our study indicate that the rate could decrease over time or that sludge composition influences the degradability of the unbiodegradable particulate fraction. But our results also demonstrate that extracellular polymeric substances (EPS) have a minor impact on the biodegradability of the unbiodegradable particulate fraction. Overall bound EPS were indeed biodegradable under all conditions and thus did not accumulate in the unbiodegradable particulate fraction. Different bound EPS pools (e.g., cation bound EPS) were associated with specific degradation behaviors. Besides improved mechanistic understanding of sludge degradation processes, our results have implications for the development of decentralized wastewater treatment technologies with on-site reduction of excess sludge. [ABSTRACT FROM AUTHOR]

Traditionally, chemical and physical methods have been used to control biofouling on membranes by inactivating and removing the biofouling layer. Alternatively, the permeability can be increased using biological methods while accepting the presence of the biofouling layer. We have investigated two different types of metazoans for this purpose, the oligochaete Aelosoma hemprichi and the nematode Plectus aquatilis . The addition of these grazing metazoans in biofilm-controlled membrane systems resulted in a flux increase of 50% in presence of the oligochaetes ( Aelosoma hemprichi ), and a flux increase of 119–164% in presence of the nematodes ( Plectus aquatilis ) in comparison to the control system operated without metazoans. The change in flux resulted from (1) a change in the biofilm structure, from a homogeneous, cake-like biofilm to a more heterogeneous, porous structure and (2) a significant reduction in the thickness of the basal layer. Pyrosequencing data showed that due to the addition of the predators, also the community composition of the biofilm in terms of protists and bacteria was strongly affected. The results have implications for a range of membrane processes, including ultrafiltration for potable water production, membrane bioreactors and reverse osmosis. [ABSTRACT FROM AUTHOR]

On-site minimization of excess sludge production is a relevant strategy for the operation of small-scale and decentralized wastewater treatment plants. In the study, we evaluated the potential of activated sludge systems equipped with side-stream reactors (SSRs). This study especially focused on how the sequential exposure of sludge to different aeration conditions in the side-stream reactors influences the overall degradation of sludge and of its specific fractions (active biomass, extracellular polymeric substances (EPS), EPS proteins, EPS carbohydrates). We found that increasing the solid retention time from 25 to 40 and 80 days enhanced sludge degradation for all aeration conditions tested in the side-stream reactor. Also, the highest specific degradation rate and in turn the lowest sludge production were achieved when maintaining aerobic conditions in the side-stream reactors. The different sludge fractions in terms of active biomass (quantified based on adenosine tri-phosphate (ATP) measurements), EPS proteins and EPS carbohydrates were quantified before and after passage through the SSR. The relative amounts of active biomass and EPS to volatile suspended solids (VSS) did not changed when exposed to different aeration conditions in the SSRs, which indicates that long SRT and starvation in the SSRs did not promote the degradation of a specific sludge fraction. Overall, our study helps to better understand mechanisms of enhanced sludge degradation in systems operated at long SRTs. [ABSTRACT FROM AUTHOR]

Biofilms in drinking water distribution systems (DWDS) could exacerbate the persistence and associated risks of pathogenic Legionella pneumophila (L. pneumophila), thus raising human health concerns. However, mechanisms controlling adhesion and subsequent detachment of L. pneumophila associated with biofilms remain unclear. We determined the connection between L. pneumophila adhesion and subsequent detachment with biofilm physical structure characterization using optical coherence tomography (OCT) imaging technique. Analysis of the OCT images of multispecies biofilms grown under low nutrient condition up to 34 weeks revealed the lack of biofilm deformation even when these biofilms were exposed to flow velocity of 0.7 m/s, typical flow for DWDS. L. pneumophila adhesion on these biofilm under low flow velocity (0.007 m/s) positively correlated with biofilm roughness due to enlarged biofilm surface area and local flow conditions created by roughness asperities. The preadhered L. pneumophila on selected rough and smooth biofilms were found to detach when these biofilms were subjected to higher flow velocity. At the flow velocity of 0.1 and 0.3 m/s, the ratio of detached cell from the smooth biofilm surface was from 1.3 to 1.4 times higher than that from the rough biofilm surface, presumably because of the low shear stress zones near roughness asperities. This study determined that physical structure and local hydrodynamics control L. pneumophila adhesion to and detachment from simulated drinking water biofilm, thus it is the first step toward reducing the risk of L. pneumophila exposure and subsequent infections. [ABSTRACT FROM AUTHOR]

Fouling layers developing on membrane filters can display significant spatial heterogeneity (roughness), yet the effect of fouling layer spatial distribution on hydraulic resistance has not been studied systematically. We used simple flux models, based on Darcy׳s law, to assess the impact of spatial distribution on resistance and permeate flux. Our results show that, for a given mean fouling layer thickness, greater spatial heterogeneity could increase fluxes by over an order of magnitude. The degree of error depended on the membrane resistance, fouling layer permeability, and the characteristics of the spatial distribution. We developed 1-dimensional and 2-dimensional flow models, both considering spatial heterogeneity, to improve the accuracy of the conventional model. The proposed models were validated with experimental data from a gravity driven membrane filter with a fouling layer having a high degree of spatial heterogeneity. Accounting for spatial heterogeneity significantly improved the prediction of permeate flux. [ABSTRACT FROM AUTHOR]

This study investigated the influence of inorganic particles on the hydraulic resistance of biofilm grown on membrane surface during low-pressure dead-end ultrafiltration. Gravity-driven ultrafiltration membrane systems were operated during several weeks without any flushing or cleaning. Smaller (kaolin d 0.5 = 3.6 μm) or larger (kaolin with diatomaceous earth 50/50%, d 0.5 = 18.1 μm) particles were added to pre-filtered creek water or to unfiltered creek water. It was demonstrated in both experiments that presence of finer particles in the feed water (kaolin) induced formation of compact and homogeneous biofilm structure. On the other hand presence of the larger particles (diatomite) helped to counterbalance the effect of fine particles due to the formation of more heterogeneous and permeable biofilm structure. The hydraulic resistance of biofilms formed with fine particles was significantly higher than the resistance of biofilm formed in (1) absence of any inorganic particles or (2) in presence of the mixed particle population. The membrane orientation (vertical or horizontal) determined which particles were accumulating at the membrane surface, with structural differences shown by Scanning Electron Microscopy (SEM). For vertical membranes, the larger particles were selectively removed due to sedimentation and did not contribute to the biofilm development. Thus the selection of smaller particles due to vertical membrane configuration negatively affected the biofilm structure and permeation rates, and such selective accumulation of fine particles should be avoided. [ABSTRACT FROM AUTHOR]

Highlights: [•] EPS distribution was studied in two biofilms showing different microbial populations. [•] Cohesive layers of the biofilms were evidenced by applying hydrodynamic shear. [•] EPS content did not relate to biofilm cohesive properties. [•] For the first time hydrophobic EPS in biofilms were characterized using HIC method. [•] The strength of hydrophobic interactions seemed to be related to microbial activity. [Copyright &y& Elsevier]

Immune tolerance induction ( ITI) can eliminate factor VIII ( FVIII) inhibitory antibodies that appear during FVIII replacement therapy. If first-line ITI fails, switching to a different FVIII concentrate, especially one containing von Willebrand factor ( VWF), has been advocated. The objective of the study was to assess the efficacy and safety of Haemate® P, a plasma-derived FVIII concentrate containing high levels of VWF, as ITI in severe haemophilia A patients who had failed at least one prior ITI attempt with a different FVIII concentrate. In this multicentre, observational study, Haemate® P was administered at a starting dose of 83-308 IU kg−1 day−1 (1500-6000 IU day−1). Efficacy was assessed by standard criteria (e.g. Bethesda titre, FVIII recovery and half-life), and bleeding characteristics. Nine patients from six haemophilia centres were treated with Haemate® P after failing one ( n = 2), two ( n = 5) or three ( n = 2) prior ITI courses. The median time from inhibitor detection to Haemate® P treatment was 5.4 years. The median Haemate® P dose was 134 IU kg−1, and the median treatment duration 32 months. During median of 47 months of follow-up, complete response, partial response and treatment failure were observed in one, three and five patients respectively. Five patients experienced seven adverse events (AEs), including two serious AEs (sepsis). Haemate® P was discontinued due to an AE in one patient with a partial response. Haemate® P salvage ITI resulted in complete or partial tolerization in four of nine patients (44%) who had failed previous ITI attempts using different FVIII concentrates. [ABSTRACT FROM AUTHOR]

Abstract: Extracellular Polymeric Substances (EPS) analysis was undertaken on three biofilms grown under different feeding conditions and offering diverging microbial activities and structural characteristics. EPS were extracted by a multi-method protocol including sonication, Tween and EDTA treatments and were characterized by size exclusion chromatography (SEC). Tween and sonication extracts presented higher EPS size diversity compared to EDTA extracts. EPS size diversity also increased with microbial functions within the biofilms and a specific 25–50 kDa cluster was identified only in extracts from biofilms presenting autotrophic activity. Another specific size cluster (180 kDa) occurred in Tween extracts provided from the mechanically stable biofilms. Such specific EPS appear as potential indicators for describing microbial and structural properties of biofilms. This study brings new elements for designing EPS fractionation and shows that size distribution analysis is an interesting tool to relate EPS diversity with macro-scale characteristics of biofilms. [ABSTRACT FROM AUTHOR]

Recombinant activated factor VII (rFVIIa) has recently been introduced for improving haemostasis in haemophiliac patients developing alloantibodies (inhibitors) to factor VIII (FVIII) or factor IX (FIX). We describe the successful management of haemorrhagia with rFVIIa in five different situations: an episode of surgical bleeding in a patient with haemophilia A and non-surgical haemorrhages in four patients with haemophilia A, acquired haemophilia, congenital severe FV defect and pseudo-acquired haemophilia, respectively. In each case, rFVIIa was effective and safe. There is no doubt that rFVIIa is useful in the therapeutic management of patients with antibodies to FVIII or FIX. However, the treatment is expensive and a cost-effectiveness analysis would be useful. [ABSTRACT FROM AUTHOR]

Biofouling layer (i.e., biofilm) is an inevitable presence for the membrane filtration processes. In this study, we elucidated biofouling formation from the perspective of affecting the attachment of bacteria for the first time, whereby the role of initial available biopolymers was revealed. Results demonstrated that the presence of initial available biopolymers increased the abundance of the genus Caulobacter , which was capable of mineralizing biopolymers; whereas, for the typically oligotrophic species of Polynucleobacter , it exhibited low abundance. Greater concentrations of polysaccharides and proteins were accumulated in the biofouling layer, when provided with initial biopolymers, and the biofilm structure was more heterogeneous with larger pore size and higher thickness. Thereby, the corresponding filtration system exhibited greater permeability and better removal performance of organics. Collectively, the initial available biopolymers altered the attachment conditions for the bacteria, which subsequently impacted the bacterial community, and in turn biofilm composition, physical structure and filtration performance. [Display omitted] • Biofouling was firstly explored from perspective of affecting bacterial attachment. • Presence of initial available biopolymers could alter biofilm bacterial community. • Discrepancy in microbial community differed biofilm composition and structure. • Higher porosity in biofouling layer led to lower hydraulic resistance. [ABSTRACT FROM AUTHOR]

Introduction: Turoctocog alfa (NovoEight®) is a B‐domain‐truncated recombinant factor VIII (FVIII) approved for patients with haemophilia A. Aim: To investigate the long‐term safety and efficacy of turoctocog alfa in routine clinical practice. Methods: Guardian 5 was a prospective, multinational, non‐interventional, post‐authorisation safety study. Male previously treated patients (> 150 exposure days [EDs]) of any age with severe/moderately severe haemophilia A (FVIII ≤ 2%) and a negative inhibitor test prior to first dosing (independent of FVIII‐inhibitor history) were included to receive prophylaxis or on‐demand treatment. The primary endpoint was the proportion of patients developing FVIII inhibitors (≥.6 Bethesda Units [BU]) after baseline visit, measured as per routine practice of each study site during clinic visits. Secondary endpoints included haemostatic effect, annualised bleeding rate (ABR), and adverse reactions assessment. The study concluded when 50 patients reached 100 EDs/patient minimum. Results: Seventy patients were screened and 68 exposed to turoctocog alfa; 63 (92.6%) were on prophylaxis and five received on‐demand treatment. Six (8.8%) patients reported a history of positive inhibitors. During the study, patients were exposed to turoctocog alfa for a mean (standard deviation) of 131.9 (99.0) days/patient. Fifty‐five of 58 patients who completed the study were tested for FVIII inhibitors; no positive tests were reported. Overall success rate of turoctocog alfa for treatment of bleeds was 87.3%. Among patients receiving prophylaxis, median (range) ABR was 1.97 (.0–25.5) bleeds/year; estimated ABR (negative binomial model) was 3.65 (95% confidence interval: 2.53–5.25). Conclusion: Turoctocog alfa was safe and efficacious for haemophilia A treatment in routine clinical practice. [ABSTRACT FROM AUTHOR]

[Display omitted] • ALE hydrogels successfully remove phosphate from real municipal wastewater. • Acidic pH conditions reduce phosphate sorption by ALE hydrogels. • Phosphate removal occurs even at high NH 4 +, NO 3 −, Ca2+ and Cl− concentrations. • ALE need to be further tailored to decrease the release of structural components. • Phosphorus-rich ALE hydrogels may be further tested for land fertilization. This worked assessed the potential of alginate-like exopolymers (ALE) hydrogels recovered from aerobic granular sludge (AGS) in removing compounds commonly present in municipal wastewater. Batch sorption experiments were performed with ALE hydrogels at different operating conditions. Results showed that ALE hydrogels can only remove phosphate, at removal efficiencies of up to 90.8% and practical loadings of 1.22 ± 0.07 mg PO 4 3−-P/g TS ALE. Phosphate removal was observed even in the presence of competing ions. Moreover, neutral to acidic pH values strongly impaired the phosphate removal (28.9 ± 0.8% at pH = 6.00), while basic pH at around 8.50 was the most favourable (up to 90.8% at pH = 8.67). However, ALE hydrogels contributed to the increase in COD, total nitrogen and total phosphorus in the bulk liquid, what suggests that ALE need to be further tailored. Therefore, this study demonstrates that ALE represent a relevant approach for the recovery of phosphates from municipal wastewater. [ABSTRACT FROM AUTHOR]

We used positron emission tomography (PET) to assess the relation between combined imaging of cerebral blood flow and oxygen consumption 5-18 h after first middle cerebral artery (MCA) stroke and neurological outcome at 2 months. All 18 patients could be classified into three visually defined PET patterns of perfusion and oxygen consumption changes. Pattern I (7 patients) suggested extensive irreversible damage and was consistently associated with poor outcome. Pattern II (5) suggested continuing ischaemia and was associated with variable outcome. Pattern III (6), with hyperperfusion and little or no metabolic alteration, was associated with excellent recovery, which suggests that early reperfusion is beneficial. This relation between PET and outcome was highly significant (p < 0.0005). The results suggest that within 5-18 h of stroke onset, PET is a good predictor of outcome in patterns I and III, for which therapy seems limited. The absence of predictive value for pattern II suggests that it is due to a reversible ischaemic state that is possibly amenable to therapy. These findings may have important implications for acute MCA stroke management and for patients' selection for therapeutic trials. [ABSTRACT FROM AUTHOR]

Abstract Gravity-driven membrane (GDM) filtration has been investigated for almost 10 years. The technology is characterized not only by relatively lower transmembrane pressures which can be achieved by gravity (extremely low energy consumption), but also by the phenomenon of flux stabilization: A biofilm is allowed to form on the membrane and a stabilization of flux occurs which is related to biological processes within the biofilm layer on the membrane. This enables stable operation during a year or longer without any cleaning or flushing. Initially, the technology was developed mainly for household drinking water treatment, but in the meantime, the research and application has expanded to the treatment of greywater, rainwater, and wastewater as well as the pretreatment of seawater for desalination. This review covers the field from the rather fundamental research on biofilm morphology and microbial community analysis to the impact of feedwater composition, process parameters and organic removal performance. Not only household applications, but also for community-scale treatment and full-scale applications are discussed. In addition, the application potential is highlighted in comparison to conventional ultrafiltration. Finally, an overall assessment is illustrated and the research and development needs are identified. Highlights • Flux stabilization in gravity-driven UF has first been reported in 2010. • Many papers have described this process for water and wastewater treatment. • Mechanisms of biofilm formation and fouling have been studied. • Improved removal of dissolved compounds has been reported. • Total costs can be lower than conventional UF, depending on the scale of application. [ABSTRACT FROM AUTHOR]

Abstract Biofilm formation in membrane systems negatively impacts the filtration system performances. This study evaluated how biofilm compression driven by permeate flow increases the hydraulic resistance and leads to reduction in permeate flux. We analysed the effect of biofilm compression on hydraulic resistance and permeate flux through computational models supported by experimental data. Biofilms with homogeneous surface structure were subjected to step-wise changes in flux and transmembrane pressure during compression and relaxation tests. Biofilm thickness under applied forces was measured non-invasively in-situ using optical coherence tomography (OCT). A numerical model of poroelasticity, which couples water flow through the biofilm with biofilm mechanics, was developed to correlate the structural deformation with biofilm hydraulics (permeability and resistance). The computational model enabled extracting mechanical and hydrological parameters corresponding to the experimental data. Homogeneous biofilms under elevated compression forces experienced a significant reduction in thickness while only a slight increase in resistance was observed. This shows that hydraulic resistance of homogeneous biofilms was affected more by permeability decrease due to pore closure than by a decrease in thickness. Both viscoelastic and elastoplastic models could describe well the permanent biofilm deformation. However, for biofilms under study, a simpler elastic model could also be used due to the small irreversible deformations. The elastic moduli fitting the measured data were in agreement with other reported values for biofilm under compression. Biofilm stiffening under larger flow-driven compression forces was observed and described numerically by correlating inversely the elastic modulus with biofilm porosity. The importance of this newly developed method lies in estimation of accurate biofilm mechanical parameters to be used in numerical models for both membrane filtration system and biofouling cleaning strategies. Such model can ultimately be used to identify optimal operating conditions for membrane system subjected to biofouling. Highlights • OCT was coupled with a poroelastic Fluid-Structure Interaction biofilm model. • Mechanical properties of biofilms were determined in-situ by a non-destructive approach. • Homogeneous biofilm structure deforms reversible in compression/relaxation cycles. • Biofilm hydraulic resistance was governed by permeability change due to pore closure. • Biofilm stiffening at large fluxes can be explained by a reduction in porosity. [ABSTRACT FROM AUTHOR]

This study aimed at evaluating stratification of hydraulic resistance over the depth of membrane biofilms developed during gravity driven membrane (GDM) ultrafiltration. Biofilms were grown in membrane fouling simulators (MFS) for 25 days under 3 contrasting influent conditions: nutrient enriched, phosphorus limiting, and river water influent. Shear rheology was used to determine the biofilms material characteristics (e.g., elasticity, yield stress). Optical coherence tomography (OCT) was used to determine the response of the biofilms physical structure (e.g., thickness) to increased hydraulic shear stress from 0 up to 2.6 Pa. Stratification was observed in nutrient enriched and river water biofilms and which partially detached by erosion of their rough top layer under low shear conditions. A cohesive base layer remained attached to the membrane surface under high shear conditions, indicating stratification in cohesion over the biofilms depth. Erosion of the top layer only resulted in a slight decrease in the biofilm hydraulic resistance indicating that the very cohesive and thin base layer also represent significant hydraulic resistance. Conversely, P limiting biofilms had uniform structural and mechanical characteristics, detaching by sloughing and peeling at low and high shear stress respectively. Biofilms formed under phosphorus limiting conditions had equal elasticity, yet a lower yield stress compared to nutrient enriched and river water biofilms respectively and were more susceptible to detachment. The scientific implication of the presented work demonstrates that biofilm detachment is influenced by both the structural (surface heterogeneity) and material characteristics (e.g., yield stress), with practical relevance for hydraulic resistance during GDM filtration. [ABSTRACT FROM AUTHOR]

This study investigates the functional correspondence between porescale hydrodynamics, mass transfer, pore structure and biofilm morphology during progressive biofilm colonization of a porous medium. Hydrodynamics and the structure of both the porous medium and the biofilm are experimentally measured with 3D particle tracking velocimetry and micro X-ray Computed Tomography, respectively. The analysis focuses on data obtained in a clean porous medium after 36 h of biofilm growth. Registration of the particle tracking and X-ray data sets allows to delineate the interplay between porous medium geometry, hydrodynamic and mass transfer processes on the morphology of the developing biofilm. A local analysis revealed wide distributions of wall shear stresses and concentration boundary layer thicknesses. The spatial distribution of the biofilm patches uncovered that the wall shear stresses controlled the biofilm development. Neither external nor internal mass transfer limitations were noticeable in the considered system, consistent with the excess supply of nutrient and electron acceptors. The wall shear stress remained constant in the vicinity of the biofilm but increased substantially elsewhere. [ABSTRACT FROM AUTHOR]

The effect of extracellular polymeric substances (EPS) on the meso-scale physical structure and hydraulic resistance of membrane biofilms during gravity driven membrane (GDM) filtration was investigated. Biofilms were developed on the surface of ultrafiltration membranes during dead-end filtration at ultra-low pressure (70 mbar). Biofilm EPS composition (total protein, polysaccharide and eDNA) was manipulated by growing biofilms under contrasting nutrient conditions. Nutrient conditions consisted of (i) a nutrient enriched condition with a nutrient ratio of 100:30:10 (C: N: P), (ii) a phosphorus limitation (C: N: P ratio: 100:30:0), and (iii) a nitrogen limitation (C: N: P ratio: 100:0:10). The structure of the biofilm was characterised at meso-scale using Optical Coherence Tomography (OCT). Biofilm composition was analysed with respect to total organic carbon, total cellular mass and extracellular concentrations of proteins, polysaccharides, and eDNA. 2D-confocal Raman mapping was used to characterise the functional group composition and micro-scale distribution of the biofilms EPS. Our study reveals that the composition of the EPS matrix can determine the meso-scale physical structure of membrane biofilms and in turn its hydraulic resistance. Biofilms grown under P limiting conditions were characterised by dense and homogeneous physical structures with high concentrations of polysaccharides and eDNA. Biofilm grown under nutrient enriched or N limiting conditions were characterised by heterogeneous physical structures with lower concentrations of polysaccharides and eDNA. For P limiting biofilms, 2D-confocal Raman microscopy revealed a homogeneous spatial distribution of anionic functional groups in homogeneous biofilm structures with higher polysaccharide and eDNA concentrations. This study links EPS composition, physical structure and hydraulic resistance of membrane biofilms, with practical relevance for the hydraulic performances of GDM ultrafiltration. [ABSTRACT FROM AUTHOR]

Background and Objectives: A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact® in acquired fibrinogen deficiency in real‐life medical practice in France. Materials and Methods: One hundred and fifty patients were planned for 28 days of prospective follow‐up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed. Results: One hundred and fifty‐six patients (16–87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow‐up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four‐site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%). Conclusion: The Clottafact® safety profile observed during the study matched the known profile of fibrinogen during use. [ABSTRACT FROM AUTHOR]

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent—biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling. [ABSTRACT FROM AUTHOR]

The accuracy of a biofilm reactor model depends on the extent to which physical system conditions particularly bulk-liquid hydrodynamics and their influence on biofilm dynamics) deviate from the ideal conditions upon which the model is based. It follows that an improved capacity to model a biofilm reactor does not necessarily rely on an improved biofilm model, but does rely on an improved mathematical description of the biofilm reactor and its components. Existing biofilm reactor models typically include a one-dimensional biofilm model, a process (biokinetic and stoichiometric) model, and a continuous flow stirred tank reactor (CFSTR) mass balance that [when organizing CFSTRs in series] creates a pseudo two-dimensional (2-D) model of bulk-liquid hydrodynamics approaching plug flow. In such a biofilm reactor model, the user-defined biofilm area is specified for each CFSTR; thereby, Xcarrier does not exit the boundaries of the CFSTR to which they are assigned or exchange boundaries with other CFSTRs in the series. The error introduced by this pseudo 2-D biofilm reactor modeling approach may adversely affect model results and limit model-user capacity to accurately calibrate a model. This paper presents a new sub-model that describes the migration of Xcarrier and associated biofilms, and evaluates the impact that Xcarrier migration and axial dispersion has on simulated system performance. Relevance of the new biofilm reactor model to engineering situations is discussed by applying it to known biofilm reactor types and operational conditions. [ABSTRACT FROM AUTHOR]

Background: Nonacog alfa, the recombinant Factor IX (F IX) used for the treatment of hemophilia B, was approved in Europe in 1998. A reformulated version was approved for European use in 2007.Study Design and Methods: This postmarketing study, as recommended by the risk management plan, was conducted to confirm the safety of reformulated nonacog alfa in a usual care setting in France. This open-label, noninterventional, prospective, longitudinal postmarketing study comprised 19 French hemophilia centers. Patients with hemophilia B receiving reformulated nonacog alfa for prophylaxis or on-demand treatment were followed up on usual care schedule.Results: A total of 58 subjects were enrolled, of whom 29 (50%) were less than 18 years of age. Hemophilia was severe (baseline F IX activity < 1%) in 47 (81%) patients. All subjects except one were already treated with reformulated nonacog alfa before enrollment. One subject was receiving reformulated nonacog alfa as immune tolerance induction at time of enrollment. At enrollment, treatment regimen was mainly prophylactic in subjects less than 18 years and on-demand in subjects 18 years or older. Median duration of follow-up in the survey was 3.3 (2.3-3.8) years. The median annualized bleeding rate was 3.9 (1.5-5.2) for prophylaxis regimen and 12.2 (3.9-22.1) for on-demand regimen. One subject, a previously untreated patient, developed F IX inhibitors during follow-up. No allergic reaction, no blood cell agglutination, no lack of efficacy or recovery, and no thrombotic events were reported.Conclusion: Reformulated nonacog alfa was shown to be safe in a usual care setting. [ABSTRACT FROM AUTHOR]