Disease activity-guided tapering of biologics in patients with inflammatory arthritis: a pragmatic, randomized, open-label, equivalence trial.

OBJECTIVE: To evaluate whether disease activity-guided tapering of biologics compared to continuation as usual care enables a substantial dose reduction while disease activity remains equivalent. METHOD: In this pragmatic, randomized, open-label, equivalence trial, adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in low disease activity on stable-dose biologics for ≥ 12 months were randomized 2:1 into either the tapering group, i.e. disease activity-guided prolongation of the biologic dosing interval until flare or withdrawal, or the control group, i.e. maintaince of baseline biologics with a possible small interval increase at the patients request. The co-primary outcome in the intention-to-treat population was met if superiority in ≥ 50% biologic reduction at 18 months was demonstrated and disease activity was equivalent (equivalence margins ± 0.5). RESULTS: Ninety-five patients were randomized to tapering and 47 to control, of whom 37% (35/95) versus 2% (1/47) achieved ≥ 50% biologic reduction at 18 months. The risk difference was statistically significant [35%, 95% confidence interval (CI) 24%-45%], while disease activity remained equivalent [mean difference 0.05, 95% CI -0.12-0.29]. A statistically significant flare risk was observed [tapering 41% (39/95) vs control 21% (10/47), risk difference 20%, 95% CI 4%-35%]; but, only 1% (1/95) and 6% (3/47) had persistent flare and needed to switch to another biological drug. CONCLUSIONS: Disease activity-guided tapering of biologics in patients with inflammatory arthritis enabled one-third to achieve ≥ 50% biologic reduction, while disease activity between groups remained equivalent. Flares were more frequent in the tapering group but were managed with rescue therapy.

Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial.

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.

Plasma concentrations of alpha-1-acid glycoprotein in preterm and term newborns: influence of mode of delivery and implications for plasma protein binding of local anaesthetics.

BACKGROUND: Alpha-1-acid glycoprotein (AAGP) is an acute-phase protein with high affinity for amide local anaesthetics (LAs), and a major determinant of free and potentially toxic concentrations of LAs in plasma. Neonates are known to have lower plasma concentrations of AAGP than adults, and are at risk of developing high free concentrations of LAs. Data regarding AAGP in newborns are so far sparse. The aim of this study was to determine plasma concentrations of AAGP after delivery of preterm and term infants, and to investigate correlations between AAGP and gestational age, birth weight, gender, and mode of delivery. METHODS: In this prospective observational study, blood was sampled from umbilical cords of 70 newborn infants born at gestational weeks 27-42 immediately after delivery. Blood samples were subsequently analysed for AAGP plasma concentrations with an immunoturbidimetric assay. RESULTS: We found higher concentrations of AAGP in infants born vaginally compared with those who were delivered by elective Caesarean section [median (inter-quartile range) 0.189 g litre-1 (0.142-0.263 g litre-1) vs 0.110 g litre-1 (0.094-0.157 g litre-1; P=0.0003)], respectively. There was a correlation between gestational age and AAGP concentrations (r=0.50; P=0.011), with significantly higher concentrations in the more mature infants. Gender and birth weight did not appear to influence the plasma concentrations of AAGP. CONCLUSIONS: Alpha-1-acid glycoprotein concentrations in newborns are influenced both by gestational age and mode of delivery. Thus, when dosing local anaesthetics in a parturient, these factors should be taken into account.

From 'miserable minority' to the 'fortunate few': the other end of the mild traumatic brain injury spectrum.

OBJECTIVES: This study, as part of the UPFRONT-study, aimed to study the patients that report zero complaints early after injury, a group that we named the 'fortunate few'. We focused on their demographic, clinical and premorbid characteristics, and examined whether they would remain asymptomatic. Moreover, we investigated the influence of anxiety and depression (HADS), and determined outcome (GOS-E) and quality of life (WHOQOL-BREF) 1 year after injury. METHODS: Patients with MTBI (Glasgow Coma Scale score 13-15), without complaints 2 weeks after injury were included. Follow-up took place at 3, 6 and 12 months after injury. RESULTS: Of the entire UPFRONT-cohort (n = 1151), 10% (n = 119) reported zero complaints 2 weeks after injury. More than half of these patients (57%) developed complaints at a later stage (M = 2, p < .001). Patients with secondary complaints had higher anxiety (p = .004) and depression (p = .002) scores, leading to less favourable outcome (p = .014) and a lower quality of life (p = .006) 1 year after injury compared to patients that remained asymptomatic. CONCLUSION: One in 10 patients with mTBI report zero complaints early after injury. Although they seem fully recovered early after injury, a substantial part may develop secondary complaints leading to less favourable outcome and lower quality of life, warranting further research of this interesting group.

Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial.

BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up. PATIENTS AND METHODS: Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. RESULTS: Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. CONCLUSIONS: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. TRIAL NUMBERS: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).

Outpatient follow-up after mild traumatic brain injury: Results of the UPFRONT-study.

OBJECTIVE: To investigate outpatient follow-up after mild traumatic brain injury (mTBI) by various medical specialists, for both hospitalized and non-hospitalized patients, and to study guideline adherence regarding hospital admission. METHODS: Patients (n = 1151) with mTBI recruited from the emergency department received questionnaires 2 weeks (n = 879), 3 months (n = 780) and 6 months (n = 668) after injury comprising outpatient follow-up by various health care providers, and outcome defined by the Glasgow Outcome Scale Extended (GOS-E) after 6 months. RESULTS: Hospitalized patients (60%) were older (46.6 ± 19.9 vs. 40.6 ± 18.5 years), more severely injured (GCS <15, 50% vs. 13%) with more Computed Tomography (CT) abnormalities on admission (21% vs. 2%) compared to non-hospitalized patients (p < 0.01) . Almost half of the patients visited a neurologist at the outpatient clinic within six months (60% of the hospitalized and 25% of the non-hospitalized patients (χ2 = 67.10, p < 0.01)), and approximately ten per cent consulted a psychiatrist/psychologist. Outcome was unfavourable (GOS-E <7) in 34% of hospitalized and 21% of non-hospitalized patients (χ2 = 11.89, p < 0.01). CONCLUSION: Two-thirds of all mTBI patients consult one or more specialists within six months after injury, with 30% having an unfavourable outcome. A quarter of non-hospitalized patients was seen at the outpatient neurology clinic, underling the importance of regular follow-up of mTBI patients irrespective of hospital admittance.

Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.

Distinct resting-state perfusion patterns underlie psychomotor retardation in unipolar vs. bipolar depression.

OBJECTIVE: Psychomotor abnormalities characterize both unipolar (UP) depression and bipolar (BP) depression. We aimed to assess their neurobiological correlates in terms of motor activity (AL) and resting-state cerebral blood flow (rCBF) and investigate their association in BP, UP, and healthy controls (HC). METHOD: We enrolled 42 depressed patients (22 BP, 20 UP) and 19 HC matched for age, gender, education, income. AL and rCBF were objectively assessed with the use of wrist actigraphy and arterial spin labeling. Group differences and the association of AL and rCBF were computed. RESULTS: Activity level was significantly reduced in patients, but no difference was found between BP and UP. Increased perfusion was found in BP compared with UP and HC, in multiple brain areas. We found positive correlations of rCBF and AL in BP and UP, in different parts of the insula and frontal regions. Only BP showed a cluster in the left precentral gyrus. In HC, only inverse correlations of AL and rCBF were found. CONCLUSION: The differences in rCBF and in the localization of the clusters of positive AL/rCBF correlations between BP and UP suggest that different neural impairments may underlie motor symptoms in the two disorders, but finally converge in phenotypically similar manifestations.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression.

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study was to investigate FAA and its correlation with resting-state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant to reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left-lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients), in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right-lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA: cost-effectiveness based on a 2-year randomized trial.

OBJECTIVES: To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). METHOD: In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient clinics and general practice, prescription and non-prescription medicine, dietary supplements, other health-care resources, and complementary and alternative care. Measures of effectiveness and costs were collected by self-reported questionnaires at inclusion and after 12 and 24 months. Incremental cost-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. RESULTS: Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. CONCLUSIONS: Shared care and nurse care seem to cost less but provide broadly similar health outcomes compared with rheumatologist outpatient care. However, it is still uncertain whether nurse care and shared care are cost-effective in comparison with rheumatologist outpatient care.

A systematic insight into a single-stage deammonification process operated in granular sludge reactor with high-loaded reject-water: characterization and quantification of microbiological community.

AIMS: Reject-water from sludge dewatering was treated in a single-stage deammonification reactor. The aims were to characterize the microbiological community within deammonification granules. METHODS AND RESULTS: In situ mapping of the intact granular sludge were made with fluorescent in situ hybridization (FISH). The Planctomycetes community in the destroyed granular sludge was characterized by FISH, polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), cloning and sequence analysis. CONCLUSIONS: AOB within Betaproteobacteria were concentrated within the first 50-100 µm of the granule, and Planctomycetes in the first 100-200 µm were responsible for nitrogen elimination. PCR-DGGE verified the higher diversity of Planctomycetes in the deammonification reactor than the anaerobic cultivation. The sequence analysis after PCR-DGGE and cloning identified the dominant Planctomycetes species for anammox reaction as Ca. Brocadia fulgida (accession no. EU478693). FISH detection using the universal probe AMX368 specific for all anammox bacteria including Ca. Brocadia fulgida failed; however, the probe BFU613 specific for Ca. Brocadia fulgida gave clear positive FISH signals. The three-dimensional structure of the ribosome may hinder binding of the universal probe to the corresponding 16S rRNA region. SIGNIFICANCE AND IMPACT OF THE STUDY: A combination of multiple methods for the analysis of the microbiological community was necessary. Oligonucleotide probes should be carefully selected, and a negative FISH analysis has to be verified by other molecular biological techniques.

[Grey zone lymphomas: limitations of the classification of aggressive B-cell lymphomas]. / Grauzonenlymphome : Grenzbereiche der Klassifikation aggressiver B-Zell-Lymphome.

Grey zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical or genetic reasons. As a defining criterion they present with features of two overlapping entities or features that are intermediate. Such lymphomas may represent a grey zone in the differentiation between indolent and aggressive lymphomas. Often they may show morphological features of one entity but be more related to another entity with respect to the immunophenotype and/or genetic constitution, such as lymphomas in the grey zone between primary mediastinal large B-cell lymphoma and primary nodal diffuse large B-cell lymphoma. The B-cell lymphoma, unclassified, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma has recently been recognized as a provisional category in the updated WHO 2008 classification of malignant lymphomas. This corresponds to a practical lymphoma category that obviously contains several entities with a Burkitt-like appearance and aggressive clinical behavior. Genetically, tumors in this category are frequently characterized by an atypical MYC translocation and complex karyotypic alterations. As yet, no adequate therapy concept exists.

[Round robin test for detection of genomic aberrations in non-Hodgkin lymphoma by in situ hybridization]. / Ringversuch zum Nachweis genomischer Veränderungen bei Non-Hodgkin-Lymphomen mittels In-situ-Hybridisierung.

BACKGROUND: The detection of characteristic genomic aberrations by fluorescence in situ hybridization (FISH) has a high diagnostic impact on lymphomas according to the World Health Organization (WHO). To investigate the reproducibility of non-isotopic ISH results a multicenter trial was carried out involving eight institutes for hematopathology. MATERIAL AND METHODS: Analyses were performed on two diffuse large B-cell lymphomas (DLBCL) without known aberrations, on one follicular lymphoma with a IGH/BCL2 translocation and BCL6 split and on two B-cell lymphomas intermediate between DLBCL and Burkitt's lymphoma with c-MYC and BCL2 rearrangements, one with an additional BCL6 split. Break-apart probes for BCL6 and c-MYC, as well as fusion probes for the c-MYC/IGH and the IGH/BCL2 translocations were used. RESULTS: All aberrations were correctly detected by all centres and no false positive or false negative results were obtained. The numbers of positive cells varied from 25% to 94%. Pearson's correlation coefficient between the centres was always > 0.8. CONCLUSIONS: The ISH analysis of recurrent genomic aberrations in formalin-fixed paraffin-embedded (FFPE) tissue is a highly reproducible technique which yields substantial additive help for lymphoma diagnostics.

Does light-based tertiary treatment prevent the spread of antibiotic resistance genes? Performance, regrowth and future direction.

The common occurrence of antibiotic-resistance genes (ARGs) originating from pathogenic and facultative pathogenic bacteria pose a high risk to aquatic environments. Low removal of ARGs in conventional wastewater treatment processes and horizontal dissemination of resistance genes between environmental bacteria and human pathogens have made antibiotic resistance evolution a complex global health issue. The phenomenon of regrowth of bacteria after disinfection raised some concerns regarding the long-lasting safety of treated waters. Despite the inactivation of living antibiotic-resistant bacteria (ARB), the possibility of transferring intact and liberated DNA containing ARGs remains. A step in this direction would be to apply new types of disinfection methods addressing this issue in detail, such as light-based advanced oxidation, that potentially enhance the effect of direct light interaction with DNA. This study is devoted to comprehensively and critically review the current state-of-art for light-driven disinfection. The main focus of the article is to provide an insight into the different photochemical disinfection methods currently being studied worldwide with respect to ARGs removal as an alternative to conventional methods. The systematic comparison of UV/chlorination, UV/H2O2, sulfate radical based-AOPs, photocatalytic processes and photoFenton considering their mode of action on molecular level, operational parameters of the processes, and overall efficiency of removal of ARGs is presented. An in-depth discussion of different light-dependent inactivation pathways, influence of DBP and DOM on ARG removal and the potential bacterial regrowth after treatment is presented. Based on presented revision the risk of ARG transfer from reactivated bacteria has been evaluated, leading to a future direction for research addressing the challenges of light-based disinfection technologies.

Pilot-scale anaerobic submerged membrane bioreactor (AnSMBR) treating municipal wastewater: the fouling phenomenon and long-term operation.

An anaerobic submerged membrane bioreactor (AnSMBR) on pilot-scale treating a mixture composed of municipal wastewater and glucose under mesophilic temperature conditions was operated for 206 days. The performance of the AnSMBR was evaluated at different fluxes, biomass concentrations and gas sparging velocities (GSV). GSV was used to control fouling. In addition, the AnSMBR was operated in cycles that included relaxation and backwashing phases. The increase in the transmembrane pressure (fouling rate) was measured under different operational conditions and was used to evaluate the stability of the process. The fouling rate could be controlled for a long period of time at a flux of 7 l m(-2) h(-1) with a GSV of 62 m/h and an average biomass concentration of 14.8 g TSS/L. The membrane was physically cleaned after 156 days of operation. The cleaning efficiency was almost 100% indicating that no irreversible fouling was developed inside the pores of the membrane. The COD removal efficiency was close to 90%. As in anaerobic processes, nutrients were not exposed to degradation and almost no pathogens were found in the effluent, hence the effluent could be used for irrigation in agriculture.

Disentangling the effects of age and mild traumatic brain injury on brain network connectivity: A resting state fMRI study.

INTRODUCTION: Cognitive complaints are common shortly after mild traumatic brain injury (mTBI) but may persist up to years. Age-related cognitive decline can worsen these symptoms. However, effects of age on mTBI sequelae have scarcely been investigated. METHODS: Fifty-four mTBI patients (median age: 35 years, range 19-64 years, 67% male) and twenty age- and sex-matched healthy controls were studied using resting state functional magnetic resonance imaging in the sub-acute phase. Independent component analysis was used to identify intrinsic connectivity networks (ICNs). A multivariate approach was adopted to evaluate the effects of age and group on the ICNs in terms of (static) functional network connectivity (FNC), intensities of spatial maps (SMs) and time-course spectral power (TC). RESULTS: We observed significant age-related changes for a) FNC: changes between 10 pairs of ICNs, mostly involving the default mode (DM) and/or the cognitive-control (CC) domains; b) SMs: intensity decrease in clusters across three domains and intensity increase in clusters across two domains, including the CC but not the DM and c) TC: spectral power decrease within the 0-0.15 Hz range and increase within the 0.20-0.25 Hz range for increasing age within networks located in frontal areas, including the anterior DM. Groups only differed for TC within the 0.065-0.10 Hz range in the cerebellar ICN and no age × group interaction effect was found. CONCLUSIONS: We showed robust effects of age on connectivity between and within ICNs that are associated with cognitive functioning. Differences between mTBI patients and controls were only found for activity in the cerebellar network, increasingly recognized to participate in cognition. Our results suggest that to allow for capturing the true effects related to mTBI and its effects on cognitive functioning, age should be included as a covariate in mTBI studies, in addition to age-matching groups.

Modelling waste stabilisation ponds with an extended version of ASM3.

In this paper an extended version of IWA's Activated Sludge Model No 3 (ASM3) was developed to simulate processes in waste stabilisation ponds (WSP). The model modifications included the integration of algae biomass and gas transfer processes for oxygen, carbon dioxide and ammonia depending on wind velocity and a simple ionic equilibrium. The model was applied to a pilot-scale WSP system operated in the city of Florianópolis (Brazil). The system was used to treat leachate from a municipal waste landfill. Mean influent concentrations to the facultative pond of 1,456 g(COD)/m(3) and 505 g(NH4-N)/m(3) were measured. Experimental results indicated an ammonia nitrogen removal of 89.5% with negligible rates of nitrification but intensive ammonia stripping to the atmosphere. Measured data was used in the simulations to consider the impact of wind velocity on oxygen input of 11.1 to 14.4 g(O2)/(m(2) d) and sun radiation on photosynthesis. Good results for pH and ammonia removal were achieved with mean stripping rates of 18.2 and 4.5 g(N)/(m(2) d) for the facultative and maturation pond respectively. Based on measured chlorophyll a concentrations and depending on light intensity and TSS concentration it was possible to model algae concentrations.

Particulate substrate retention in plug-flow and fully-mixed conditions during operation of aerobic granular sludge systems.

Particulate substrate (XB) is the major organic substrate fraction in most municipal wastewaters. However, the impact of XB on aerobic granular sludge (AGS) systems is not fully understood. This study evaluated the physical retention of XB in AGS sequencing batch reactor (SBR) during anaerobic plug-flow and then aerobic fully-mixed conditions. The influence of different sludge types and operational variables on the extent and mechanisms of XB retention in AGS SBR were evaluated. XB mass-balancing and magnetic resonance imaging (MRI) were applied. During the anaerobic plug-flow feeding, most XB was retained in the first few cm of the settled sludge bed within the interstitial voids, where XB settled and accumulated ultimately resulting in the formation of a filter-cake. Sedimentation and surface filtration were thus the dominant XB retention mechanisms during plug-flow conditions, indicating that contact and attachment of XB to the biomass was limited. XB retention was variable and influenced by the XB influent concentration, sludge bed composition and upflow feeding velocity (vww). XB retention increased with larger XB influent concentrations and lower vww, which demonstrated the importance of sedimentation on XB retention during plug-flow conditions. Hence, large fractions of influent XB likely re-suspended during aerobic fully-mixed conditions, where XB then preferentially and rapidly attached to the flocs. During fully-mixed conditions, increasing floc fractions, longer mixing times and larger XB concentrations increased XB retention. Elevated XB retention was observed after short mixing times < 60 min when flocs were present, and the contribution of flocs towards XB retention was even more pronounced for short mixing times < 5 min. Overall, our results suggest that flocs occupy an environmental niche that results from the availability of XB during aerobic fully-mixed conditions of AGS SBR. Therefore, a complete wash-out of flocs is not desirable in AGS systems treating municipal wastewater.

Effective diffusivities and mass fluxes in fungal biopellets.

Mass transport within biological aggregates is a key process that can determine overall turnover rates in submerged cultivations. A parameter commonly used for its description is the effective diffusion coefficient D(eff), which is highly dependent on biomass density and structure. Different approaches have been used to estimate or measure D(eff), yet the data still shows broad scattering. This study provides experimental data on effective diffusivities of oxygen within fungal pellets. A correlation is found with the hyphal gradient (dh/dr), which is a morphological parameter describing the structure of the pellet periphery. Furthermore, the dependency of D(eff) on fluid dynamic conditions at the pellet is investigated. The comparison of the results with data from literature clearly demonstrates the influence of the experimental methodology applied for determination of D(eff). Moreover, it is shown that while diffusion limitation of whole pellets is mainly a function of size, the influence of advection in the outer zone of pellets that is supplied with oxygen is actually rather high. Thus, it is concluded that the effective diffusion coefficient might not be sufficient for the description of mass transport within the pellet periphery for a broad range of realistic fluid dynamic conditions during cultivation. Nevertheless, although actual mass transport rates inside pellets are unknown, mass fluxes can be calculated on the basis of spatially resolved data of oxygen and biomass distribution within the pellet.

Dense astrophysical plasmas.

Degenerate bodies composed primarily of dense hydrogen and helium plasmas range from giant planets to the so far hypothetical brown dwarfs. More massive objects begin their lives as nondegenerate stars and may end as white dwarfs, composed primarily of carbon and oxygen, or as neutron stars, with solid crusts of iron or heavier elements and cores of neutron matter. The physical properties of dense plasmas that are necessary to construct theoretical models of such degenerate stars include the equation of state, transport properties, and nuclear reaction rates.