In tertiary wastewater desalination, effective minimization and cleaning of membrane fouling requires an understanding of the physicochemical interactions between conditioning film–membrane surface, ...conditioning film–bacteria, bacteria–EPS and within the EPS. In this study, the effect of conditioning film on the attachment of bacteria and EPS (isolated from RO membrane biofouling layers) to the surface was analyzed using quartz crystal microbalance with dissipation (QCM-D) equipped with polyamide-coated sensors. A conditioning film originated from membrane bioreactor (MBR) ultra-filtration permeate (UFP), mainly consisting of effluent organic matter (EfOM). This conditioning film was shown to enhance bacterial attachment but had no effect on the EPS adsorption. Furthermore, the UFP and EPS were characterized and their effects on the swelling behavior of the model polyamide surface were delineated using QCM-D by altering pH values from 6 to 8 and back to 6. In parallel, fouling experiments with UFP and EPS were conducted in a parallel RO plate and frame unit. Reversible changes in the RO permeate flux were observed as pH values were altered (from 6 to 8 and back to 6) with pristine and fouled membrane with EPS. In contrast, irreversible flux decline was observed for the UFP fouled membrane: pH variation, back to 6, promoted further interaction between the UFP organic matter and the membrane, leading to a further reduced membrane permeability. These results are likely related to the swelling phenomenon and its inhibition by the UFP layers observed in the QCM-D. More studies need to be carried out in order to analyze the effects of humic substances, abundant in the UFP fouling layer, that irreversibly interact with the polyamide surface. Reduced membrane swelling capability, which is important for water transport, by different foulants is proposed as additional RO membrane fouling mechanism.
•UF permeate conditioning film enhances bacterial attachment but has no effect on EPS adsorption.•UF permeate from MBR inhibits swelling of polyamide.•Conditioning the membrane with UF permeate from MBR irreversibly reduces permeate flux.•Reduced membrane swelling capability is proposed as additional RO membrane fouling mechanism.
Backwash procedures for deep bed filters were evaluated and compared by means of a new integrated approach based on productivity. For this, different backwash procedures were experimentally evaluated ...by using a pilot plant for direct filtration. A standard backwash mode as applied in practice served as a reference and effluent turbidity was used as the criterion for filter run termination. The backwash water volumes needed, duration of the filter-to-waste period, time out of operation, total volume discharged and filter run-time were determined and used to calculate average filtration velocity and average productivity.
Results for filter run-times, filter backwash volumes, and filter-to-waste volumes showed considerable differences between the backwash procedures. Thus, backwash procedures with additional clear flushing phases were characterised by an increased need for backwash water. However, this additional water consumption could not be compensated by savings during filter ripening. Compared to the reference backwash procedure, filter run-times were longer for both single-media and dual-media filters when air scour and air/water flush were optimised with respect to flow rates and the proportion of air and water. This means that drinking water production time is longer and less water is needed for filter bed cleaning. Also, backwashing with additional clear flushing phases resulted in longer filter run-times before turbidity breakthrough.
However, regarding the productivity of the filtration process, it was shown that it was almost the same for all of the backwash procedures investigated in this study. Due to this unexpected finding, the relationships between filter bed cleaning, filter ripening and filtration performance were considered and important conclusions and new approaches for process optimisation and resource savings were derived.
•The backwash mode had no impact on the efficiency of drinking water production.•The amount of captured particles is equal to the amount of particles carried away.•Opportunities for resource savings arise.•A new approach for optimisation of the entire filtration process was proposed.
The impact of shear stress and increases in pH on the release of natural dissolved organic matter (DOM) from Fe-DOM and Al-DOM flocs was investigated for a high organic matter, low turbidity raw ...water by application of a dynamic extinction probe (DEP) and liquid chromatography organic carbon detection (LC-OCD). It was shown that high shear forces resulted in a breakage of Fe-DOM flocs. Re-growth took place during subsequent low shear phases. However, re-growth was limited. The flocs regained a size of about 50% of the size after initial coagulation. Cyclic shearing resulted in slower re-growth rates. A new insight was that when enough time was given, similar sizes of the re-grown flocs were regained.
As shown by bulk DOC, only an insignificant release of DOM took place when flocs were exposed to shear. Increase in shear stress resulted in smaller flocs with higher specific outer surface area. However, DOM removal did not change. Thus, there was no increase in adsorption capacity due to floc breakage. Consequently, DOM must be adsorbed inside the amorphous flocs rather than on the outer surface. Also, as shear results in more compact flocs, compaction does not have an effect on DOM removal.
A pH increase of 0.5, as it can happen during water treatment after coagulation, resulted in a release of DOM. Humic substances accounted for the largest proportion of total DOM released. The increase in pH did not affect floc size. Consequently, DOM removal is mainly governed by the dependence of DOM properties on pH with the final pH determining the degree of DOM removal and not the path on which this pH is reached. The physical properties of the flocs have no impact on DOM removal.
Display omitted
► Floc breakage does not result in a release of organic matter from flocs. ► Repeated breakage of flocs results in slower re-growth. ► DOM is adsorbed in the inner pores of the flocs rather than at the outer surface. ► Increase in pH results in the release of organic matter from flocs. ► Release and removal of DOM by changes in pH are completely reversible.
Purpose
Recombinant hCG (r‐hCG) was approved in Japan in 2016. As a prerequisite for a Phase III study in Japan related to this approval, the pharmacokinetic (PK) profile of r‐hCG was investigated.
...Methods
An open‐label, partly randomized, single‐center, single‐dose, group‐comparison, Phase I PK‐bridging study was done that compared a single 250 μg dose of r‐hCG with a single 5000 IU dose of urinary hCG (u‐hCG) in healthy Japanese women, as well as comparing a single 250 μg dose of r‐hCG in Japanese and Caucasian women. The Japanese participants were randomized 1:1 to receive either r‐hCG or u‐hCG, while the Caucasian participants were weight‐matched to the Japanese participants who were receiving r‐hCG in a 1:1 fashion. The primary PK parameters were the area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC0–∞) and the maximum serum concentration (Cmax).
Results
The mean serum hCG concentration–time profiles of r‐hCG in the Japanese and Caucasian participants were a similar shape, but the level of overall exposure was ~20% lower in the Japanese participants. For the Japanese participants, r‐hCG resulted in an 11% lower Cmax but a 19% higher AUC0–∞ compared with u‐hCG. No new safety signal was identified.
Conclusion
This study cannot exclude a potential difference in the PK profile of r‐hCG between Japanese and Caucasian participants. However, this study does not indicate that there are clinically relevant differences in the serum PK of r‐hCG and u‐hCG in the Japanese participants.
Purpose
We evaluated the safety, tolerability, and pharmacokinetics (PK) of EMD 525797 (DI17E6), a humanized monoclonal antibody targeting αv-integrins, in healthy subjects.
Methods
In this ...first-in-human, double-blind, placebo-controlled, randomized Phase 1 study, healthy male volunteers were consecutively assigned to 6 ascending single-dose cohorts of 35, 100, 250, 500, 1000, or 1500 mg. Per dose cohort, EMD 525797 or placebo was administered over 1 h as an intravenous 250-mL infusion to 6 and 3 volunteers, respectively. Escalation to the next dose level was based on evaluation of safety, tolerability, and PK data.
Results
Fifty-five subjects (aged 18–45 years) were randomized. Twenty-seven of 37 (73 %) subjects receiving EMD 525797 reported a total of 61 adverse events (AEs), including 38 events (in 17 subjects) considered by the investigator to be treatment related. A total of 35 AEs were reported by 14 of 18 (78 %) placebo-treated subjects. The most commonly occurring AEs were gastrointestinal disorders, abnormal laboratory values, and increased or decreased biochemistry and/or hematology values, as well as headaches, which occurred at a slightly higher frequency in the EMD 525797 group compared with placebo. There were no serious AEs or deaths. EMD 525797 PK appeared to be dose dependent, especially at lower doses.
Conclusion
Ascending single doses of EMD 525797 were shown to be safe and well tolerated. No safety concerns were identified. This study supports the ongoing investigation of EMD 525797.
Membrane processes, such as microfiltration, ultrafiltration, and nanofiltration, are increasingly used for various applications in both upstream and downstream processing. Membrane-based processes ...play a critical role in the field of separation/purification of biotechnological products, including protein production/purification. The possibility of using membranes to separate peptides from a chicken byproduct hydrolysate and the effect of the performed downstream processing on the DPP-IV dipeptidyl peptidase IV (DPP-IV) inhibitory activity of mechanical deboning chicken residue (MDCR) has been investigated. The chicken byproduct hydrolysate was prepared by enzymatic hydrolysis followed by microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) separation. Comparing all separation treatments, hydrolysates processed only by MF and UF show the best DPP-IV inhibition (59.5-60.0% at 1 mg/mL and 34.2-40.7% at 0.5 mg/mL). These samples show dose-responsive behavior. Bioactivity was correlated with molecular weight distribution profiles and average molecular weights. The nanofiltration process notably decrease the inhibitory activity, and these permeates show low DPP-IV inhibition (9.5-21.8% at 1 mg/mL and 3.6-12.1% at 0.5 mg/mL). The size-exclusion chromatography-organic carbon detection-organic nitrogen detection (LC-OCD-OND) analysis confirms that NF and RO would retain the bioactive peptides in the concentrate in comparison to MF and UF. Bioactivity was correlated with molecular weight distribution profiles and average molecular weights. Permeates after ultrafiltration show an IC
value of 0.75 mg/mL, comparable to other potent DPP-IV inhibitors derived from various food sources, and significantly more potent compared to the microfiltration sample, which shows an IC
value of 1.04 mg/mL. The average molecular weight of the permeates calculated from the SEC chromatograms was 883 g/mol for UF and 1437 g/mol for MF. Of the four membranes studied, the UF membrane shows the best separation properties with respect to maximizing the yield and up-concentration of the bioactive peptides. Overall, UF was demonstrated to be a feasible technology for the removal of the undesired high-molecular-weight substances and up-concentration of small-molecular-weight bioactive peptides from chicken byproduct hydrolysate. These peptides might exhibit biological activity and could offer several health benefits. There is a high potential for the use of bioactive peptides, and more research in this field can lead to promising results that have significant effects in the food and medical industries.
Concentrations of genetic markers for antibiotic resistance genes (ARGs) were measured in the effluents of three Norwegian wastewater treatment plants (WWTPs) and in a receiving river upstream and ...downstream of the discharge point of one WWTP. Calculations based on mass balances were carried out to evaluate the impact of river flow rates and treatment effectivity on the WWTP's contribution to the load of genetic markers in the river. At average river flow rates, the WWTP effluent contributes 5–15% to the genetic marker load of the respective river. However, at minimum river flow rates, the WWTP effluent contributes 22–55% to the loads of different genetic markers. Scenarios of an improved or worsened removal of genetic markers in the WWTP showed that a further 1-log removal using additional treatment would be sufficient to improve considerably the river water quality with respect to genetic markers. Then, at an average flow rate, the contribution of the WWTP effluent to the load of the river would be less than 2%. However, in the case of low treatment effectivity or malfunction of the WWTP, the marker load of the river would increase dramatically. Even at average flow rate, 75–92% of the marker load would then originate from the WWTP. The results demonstrate the importance of considering the flow rates and hydrologic characteristics of the recipient water body when deciding on priorities regarding the upgrade of WWTPs for further removal of ARGs.
Display omitted
•ARG concentrations in WWTP effluents found lower than at comparable sites in Europe.•WWTP contribution to ARG load of receiving river calculated using mass balances.•At average river flow rates, WWTP effluent contributes 5–15% of ARG load in river.•Calculations show effects of river flow rates and treatment effectivity on ARG loads.•Calculations of WWTP contribution to ARG load of recipients important for decision.
Introduction. This randomized, double-blind, placebo-controlled, ascending-dose study was conducted in healthy volunteers to evaluate the safety of the investigational cyanide antidote ...hydroxocobalamin. Methods. Four ascending dosing groups received intravenous doses of 2.5, 5, 7.5 or 10 g hydroxocobalamin over 7.5 to 30 minutes at a constant infusion rate. Volunteers (n = 136) randomized 3:1 to receive hydroxocobalamin or placebo underwent a 4-day in-house observation after infusion on Day 1 and follow-up visits on Days 8, 15, and 28. Results. The most common drug-related adverse events were asymptomatic and self-limiting chromaturia and reddening of the skin, which are attributed to the red color of hydroxocobalamin. Other adverse events included pustular/papular rash, headache, erythema at the injection site, decrease in lymphocyte percentage, nausea, pruritus, chest discomfort, and dysphagia. Hydroxocobalamin was associated with an increase in blood pressure in some volunteers. Blood pressure changes peaked toward the end of hydroxocobalamin infusion and typically returned to baseline levels by 4 hours postinfusion. Maximum mean changes from baseline in systolic blood pressure ranged from 22.6 to 27.0 mmHg across hydroxocobalamin doses compared with 0.2 to 6.7 mmHg in the corresponding placebo groups. Maximum mean change from baseline in diastolic blood pressure ranged from 14.3 to 25.4 mmHg across hydroxocobalamin doses compared with −3.0 to 3.8 mmHg in the corresponding placebo groups. Two allergic reactions that occurred within minutes after start of the 5- and 10-g hydroxocobalamin infusions were successfully managed with dexamethasone and/or dimethindene maleate. Conclusion. Timely intervention for acute cyanide poisoning could entail administration of an antidote in the prehospital setting based on a presumptive diagnosis. Results of this placebo-controlled study in healthy volunteers corroborate previous studies and French postmarketing experience in cyanide-exposed patients in suggesting that the safety profile of hydroxocobalamin is consistent with prehospital or hospital use.
Inorganic chloramines (mono-, di- and trichloramine) are formed in swimming pool water from the unintended reaction of free chlorine with ammonia that is introduced by bathers. Monochloramine is of ...particular interest as it is known to react further in pool water forming harmful DBPs, such carcinogenic N-nitrosodimethylamine (NDMA). During pool water treatment with granular activated carbon (GAC) filters, monochloramine is transformed by chemical reactions on the carbon surface to N
and ammonia. As ammonia is led back into the pool where it is chlorinated again under the renewed formation of inorganic chloramines, it is recommended to use GACs with a high N
yield for monochloramine transformation in pool water treatment. In this study, yields of N
and ammonia from monochloramine conversion by commercially available GACs were determined using a fixed-bed reactor system under conditions that are typical for swimming pool water treatment. The N
yields remained constant with on-going exposure of the GAC to monochloramine and ranged from 0.5% to 21.3%, depending on the type of GAC used. Correlation analyses were conducted to identify carbon properties that can determine the N
yield for monochloramine conversion, such as the amount of oxygen groups, the elemental composition and the trace metal content. It was found that the N
yield significantly correlates with the copper content of the tested carbons. Model calculations combining pool hydraulics with formation/abatement of inorganic chloramines and NDMA as well as chloramine transformations in GAC filters showed that the concentration of inorganic chloramines and carcinogenic NDMA can be decreased by a factor of ∼2, if the tested GACs could be modified to convert up to ∼50% of the monochloramine to N
.
PDF
