Here, we initially characterized the reconsolidation of an appeti

Here, we initially characterized the reconsolidation of an appetitive memory. Then, we compared appetitive reconsolidation with its aversive counterpart regarding the implication of OA in these processes, and contrasted them with previous findings obtained in the consolidation phase. Our results demonstrate that appetitive reconsolidation takes place when animals are re-exposed to the training context, as shown by the amnesic

effect of cycloheximide when applied before the reminder. In addition, the no-reinforcement during the reminder is a necessary condition for appetitive reconsolidation to Cisplatin mw occur. Remarkably, appetitive reconsolidation is neither impaired by OA receptor antagonists nor facilitated by exogenous OA, whereas aversive

reconsolidation buy Y-27632 can be interfered with by OA administration. Thus, our results indicate that appetitive reconsolidation does not involve OA signaling, while aversive reconsolidation is negatively modulated by OA. All in all, these results could constitute a step towards the identification of particular features of appetitive and aversive reconsolidation. “
“Sites within the hippocampus, amygdala and prefrontal cortex may regulate how responses maintained by cues associated with cocaine are extinguished. To test the role of various brain sites in the consolidation of cocaine-cue extinction learning, the dorsal subiculum (dSUB), rostral basolateral amygdala

(rBLA) and infralimbic prefrontal cortex (IL) were manipulated in rats. Following cocaine self-administration training (cues present, cocaine available), responding was assessed during 1-h extinction tests (cues present, no cocaine available). To study extinction consolidation specifically, the protein synthesis inhibitor anisomycin or vehicle was infused bilaterally into the dSUB, rBLA or IL either immediately following or 6 h after the first two of three extinction training Adenosine sessions. With manipulations made immediately after extinction sessions, infusions of anisomycin into the dSUB or the rBLA deterred extinction. Rats maintained elevated levels of cocaine seeking relative to vehicle despite the absence of cocaine delivery. Manipulations of IL had no effect. Control studies showed that bilateral protein synthesis inhibition in dSUB and rBLA 6 h after the extinction sessions ended was unable to deter extinction. Rats reduced cocaine seeking in the usual manner in the absence of cocaine delivery. Collectively, these findings suggest that the dSUB and rBLA are neural substrates important for consolidation of cocaine-cue extinction learning and have time-dependent roles. Understanding the contribution of individual neural substrates for cocaine-cue extinction consolidation may help guide treatment strategies aimed at enhancing cue exposure therapy in cocaine-dependent people.

14 mg mL−1) was dialyzed against Buffer C for 5 h The UV-visible

14 mg mL−1) was dialyzed against Buffer C for 5 h. The UV-visible absorption spectrum, in the presence and absence of sodium Volasertib purchase dithionite (1 mM), was recorded in the range of 200–700 nm (Lambda 35; Perkin-Elmer). The fluorescence emission spectrum of the enzyme (0.14 mg mL−1) was recorded

by exciting it at 450 nm using a fluorescence spectrometer (Jasco V-750). The apoenzyme was prepared using the acid–ammonium sulfate method (Elmorsi & Hopper, 1977). The partially purified enzyme prepared (0.14 mg mL−1) was dialyzed against KPi buffer (50 mM, pH 5.5) containing (NH4)2SO4 (2 M), glycerol (5%) and dithiothreitol (2 mM) for 24 h at 4 °C. Both UV-visible and fluorescence spectral properties were monitored to confirm the apoenzyme preparation. The prosthetic group was extracted by treating the holoenzyme (50 μg mL−1, 1 mL) with perchloric acid (10 μL of 70%) on ice for 5 min, followed by centrifugation at 22 000 g

at 4 °C. The supernatant (40 μL) was subjected to HPLC (Jasco 1100 series) using an RP-C18 column (250 × 4 mm). A chromatogram was developed using an isocratic solvent system consisting of methanol (40%) and ortho-phosphoric acid (10 mM, 60%; v/v) in water. The eluent was identified by comparing the retention time and UV-visible spectral properties with that of the authentic FAD (retention time, Entinostat 3.62 min) and FMN (retention time, 4.85 min) treated under the same conditions. Kinetic constants were determined by measuring the initial reaction velocities with varying concentrations of 1-H2NA (10–800 μM), NAD(P)H (30–800 μM) or FAD (1–200 μM) using Oxygraph. The kinetic constants (Km and Vmax) were determined by plotting the enzyme activities Lepirudin versus substrate concentrations. All kinetic experiments were repeated twice with five different enzyme preparations. SDs observed between different sets of experiments are indicated appropriately. The kinetic data for 1-H2NA and NAD(P)H were fitted with (Vmax[S]n/Kmn+[S]n), while that for FAD were fitted with

(Vmax[S]/Km+[S]). Phenanthrene-grown culture showed a bright orange color in the early-log phase (9 h), which subsided and turned to pale green as it entered the stationary phase (30 h). Metabolites from the early-log (9 h), mid-log (18 h) and stationary (30 h) phase culture were extracted, resolved by TLC and identified by comparing their Rf values and fluorescence properties with those of authentic compounds. Three metabolite spots were detected in the spent medium of the early-log phase culture, which were identified as 1-H2NA, 1,2-DHN and salicylic acid (Rf values 0.95, 0.11 and 0.9, respectively). The spent medium of the late-log phase culture showed two spots corresponding to 1-H2NA and salicylic acid; while a single spot, salicylic acid, was identified in the stationary phase culture. Phenanthrene-grown cells were able to transform salicylaldehyde to salicylic acid and catechol (Rf values 0.9 and 0.37, respectively).

In each of these large series, one patient died soon after rituxi

In each of these large series, one patient died soon after rituximab administration as a result of overwhelming disease, and the main adverse event seen in these patients was reactivation of KS, which is intriguing and may have been attributable to the rapid B-cell depletion that is observed during rituximab therapy, or an immune reconstitution inflammatory syndrome to hitherto latent antigens [47]. Bower et al. [48] demonstrated after successful rituximab therapy, a significant reduction from baseline of the CD19 B-cell count, and reductions in the levels of the inflammatory cytokines

IL-5, IL-6 and IL-10. In the largest study to date [49], Bower et al. Epacadostat identified 61 HIV-positive patients with histologically confirmed MCD (median follow-up, 4.2 years). Since 2003, 49 patients with newly diagnosed KU-60019 MCD have been treated with rituximab with (n = 14) or without (n = 35)

etoposide. With rituximab-based treatment, the overall survival was 94% (95% CI: 87–100%) at 2 years and was 90% (95% CI: 81–100%) at 5 years compared with 42% (95% CI: 14–70%) and 33% (95% CI: 6–60%) in 12 patients treated before introduction of rituximab (log-rank p < 0.001). Four of 49 rituximab-treated patients have died; three died as a result of MCD within 10 days of diagnosis, and one died as a result of lymphoma in remission of MCD. Eight of 46 patients who achieved clinical remission suffered symptomatic, histologically confirmed MCD relapse. The median time to relapse was 2 years, and all have been successfully re-treated and are alive in remission. The 2- and 5-year progression-free survival rates for all 49 patients treated with rituximab-based therapy were 85% (95% CI: 74–95%) and 61% (95% CI: 40–82%), respectively. Gerard et al. [50] compared the incidence of NHL between patients who had received rituximab or not over 4.2 years of follow-up. In the group that did not receive rituximab (n = 65), 17 patients developed patient developed NHL (incidence, 4.2 of 1000 person-years). Based on the propensity

score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio 0.09, 95% CI: 0.01–0.70). Ten Kaposi sarcoma (KS) exacerbations and one newly diagnosed KS enough were observed in nine patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy. Data from Stebbing et al. [30] showing that rising levels of HHV8 predicted relapses, suggested that combination therapy including rituximab should be considered. For immunocompetent patients the chemotherapy regimens for MCD are based on lymphoma schedules such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) [51].

The data collection was undertaken by clinical pharmacists during

The data collection was undertaken by clinical pharmacists during their routine ward visits. All delayed and omitted doses detected were classified according to the United Kingdom Medicines Information (UKMI)

risk assessment tool (UKMI, 2010)1. The omitted or delayed doses were assigned by the project lead into one of three categories as specified by the UKMI tool. A focus group of nursing and midwifery staff was conducted to examine any barriers to implementing NPSA alerts in the Trust. This group focused on the actions taken following the alert, assessed local awareness of the alert and response, and generated ideas as to how to improve the dissemination of information following alerts. Ethics approval was not needed for this study. The audit of delayed & omitted doses was completed on 18th July 2012. In total 21 wards were audited comprising of 5 medical wards, BIRB 796 5 elderly care wards, 2 medical admissions wards, 6 surgical wards, 2 paediatric wards and 1 neonatal ward. The proportion of doses omitted or delayed was 9.73% of total doses due, with 8.8% of this being omissions and 0.93% delays. Of the 520 delayed or omitted doses, 72 (14%) were risk classified as red and 123 (24%) as amber. The focus group discussed

wider aspects of the subject, relating both to omitted and delayed doses, as well as patient safety alert communication in general. The focus group concluded the main reasons selleck for omissions and delays were lack of staff to enable timely administration, unsuitable scheduled administration times and the prescription chart not being available. The major barriers to implementation of safety alerts were felt to be lack of effective communication or continuing awareness. To increase adoption of actions from alerts multiple methods of communication and close management of any changes is essential. Electronic methods should be used more effectively, and standardised locations should be used for patient safety information. In response to these audit results a week long patient safety initiative in the form of an awareness week has been

organised for June 2013 to raise awareness of the patient safety risks associated with delayed and omitted medicine doses. The Trusts medicines use pharmacy team and senior nursing staff Montelukast Sodium work together to organise this event. During this week a number of communication methods will be used to highlight this issue, these include medication safety ward champions, webcasts, staff pledges of commitment, newsletters, and better use of the Trust intranet. 1. National Patient Safety Agency (2010). Rapid response report: Reducing harm from omitted and delayed medicines in hospital. National Patient Safety Agency. 2. Rehman, B. (2010). NPSA Rapid response report: Reducing harm from omitted and delayed medicines in hospital. A tool to support local implementation. UK Medicines Information.

Currently, instituting a second pharmacy check of PTTAs is not wa

Currently, instituting a second pharmacy check of PTTAs is not warranted. 1. Dodds LJ.

Pharmacist contributions to ensuring safe and accurate transfer of written medicines-related discharge information: lessons from a collaborative audit GSK1120212 in vivo and service evaluation involving 45 hospitals in England. Eur J Hosp Pharm Published Online First: 10 February 2014. doi:10.1136/ejhpharm-2013-000418 K. Medlinskiene Hull and East Yorkshire NHS Hospitals, Hull, UK HDS is the main communication tool between hospital and general practitioners. Evaluate turnaround time for HDS and to what extent pharmacist input was required. The average turnaround time for HDS in the pharmacy was 2 h 22 min and 75% of HDS required pharmacist input. The hospital discharge summary

GDC941 (HDS) is the main method of communicating patient’s diagnostic findings, hospital management, and arrangements for post-discharge follow up to general practitioners. HDS are additionally checked by hospital pharmacists if discharge medication supply is required. It is not unusual to receive complaints from patients about long waiting times for discharge medication. The study aimed to evaluate average time of a HDS journey and extent to which pharmacist input was required. The data collection was performed during one week in November 2013 at one of three acute NHS Trust sites. All HDS received in the pharmacy had forms attached for time recordings (time a HDS was created, reached the pharmacy,

turnaround time in the pharmacy). Data from HDS with completed time recordings was retrospectively analysed with Microsoft Excel to evaluate if pharmacist input was required. Any interventions, contributions and adjustments to HDS e.g. dose changes, additional instructions, completion of stopped medication box, completion of allergy status, were classed as pharmacist input. Ethical approval was not required. A total of 196 HDS had completed forms which represented 62% (314) of all HDS received that week Carnitine palmitoyltransferase II by the pharmacy. The average time for one HDS to reach the pharmacy once it had been created was 1 h 4 min. Only 5% (10) HDS were in the pharmacy 24 h prior discharge as per trust policy.1 The average turnaround time for a HDS was 2 h 22 min, which was considerably lower on the weekend (1 h 18 min). Each HDS was collected or delivered to the ward on average within 33 min. The overall average time of HDS journey was 3 h 59 min. The majority of HDS, 75% (147), required pharmacist input. Pharmacist input was achieved by using information on inpatient drug cards, contacting ward (nurse or doctor), or both (Table 1). Table 1 Sources used for pharmacists input Drug card 70% (103) Contacting ward (doctor or nurse) 2% (3) Both 28% (44) HDS are mostly written by junior doctors and errors are often associated with this junior status.

The concentration of l-leucine could be a trigger for the Lrp-dep

The concentration of l-leucine could be a trigger for the Lrp-dependent regulation of genes that function during feast or famine (Calvo & Matthews, 1994). Because l-methionine is a key metabolite in the sulphur, methylation and trans-sulphuration pathways, the accumulation of its oxidized forms may significantly perturb cell metabolism. Thus, both l-leucine hydroxylation and l-methionine oxidation could be also involved in the metabolic regulatory network. The authors thank Ms N.Y. Rushkevich for help in gene cloning. “

Colpoda cucullus, the morphogenetic transformation was preceded by an enhancement of the in vivo protein phosphorylation level. Immunofluorescence microscopy using antiphosphoserine antibody showed that these Bortezomib phosphorylated proteins

were localized in the macronucleus and other cytoplasmic regions. Biotinylated Phos-tag/ECL assays of isolated macronuclei showed that a 33-kDa protein (p33) was localized within them. The p33 obtained from isolated macronuclei was tentatively identified as ribosomal P0 protein by LC-MS/MS analysis. In addition, among the encystment-specific phosphoproteins obtained by phosphate-affinity chromatography, the 29-, 31-, and INK 128 purchase 33-kDa proteins (p29, p31, and p33) were tentatively identified as ribosomal P0 protein, whereas the 24-kDa phosphoprotein (p24) was tentatively identified as ribosomal S5 protein. The resting cyst formation (encystment) of protozoans is a kind of cryptobiosis that involves a drastic cellular morphogenesis. The molecular mechanism of cellular differentiation during en- and excystment has been studied especially extensively in parasitic protozoans. For example, encystment-specific key proteins such as cysteine peptidase (Ebert et al., 2008), serine protease (Moon et al., 2008), and enolase (Bouyer et al., 2009; Segovia-Gamboa et al., 2010, 2011) have recently been identified in Acanthamoeba or Entamoeba. In Giardia, proteins such as cyst wall proteins, cyst wall glycopolymer biosynthetic enzymes, transcription factors, and signaling proteins have been reported to play a

role in cellular differentiation during encystment (Lauwaet et al., 2007b; Carranza & Lujan, 2010; and references GPX6 therein). In signal transduction pathways leading to en- or excystment, protein phosphorylation and dephosphorylation were shown to occur (Abel et al., 2001; Slavin et al., 2002; Ellis et al., 2003; Gibson et al., 2006; Bazán-Tejeda et al., 2007; Lauwaet et al., 2007a; Alvarado & Wasserman, 2010), and phosphorylated proteins such as 14-3-3 protein and 70-kDa heat shock protein have been shown to play a role (Alvarado & Wasserman, 2010). In free-living ciliates, on the other hand, the morphogenetic transformation that occurs during en- and excystment is poorly understood at the molecular level, although it is known that the encystment is gene-regulated (Grisvard et al.

4b) At a concentration of 500 μg mL−1, CP251 decreased


4b). At a concentration of 500 μg mL−1, CP251 decreased

the number of bacteria from 7.84 × 104 to 3.60 × 102 CFU mL−1 (the bactericidal rate was 99.5%). While the DTPA decreased the growth of V. parahaemolyticus from 7.84 × 104 to 8.90 × 103 CFU mL−1 (the bactericidal rate was 87.4%), and CP252 caused a decrease in growth of V. parahaemolyticus from7.84 × 104 to 2.21 × 103 CFU mL−1 (the bactericidal rate was 95.9%) at the same concentration. CP251 also effectively inhibited the growth of E. coli, decreasing the number of bacteria from 3.76 × 104 to 1.62 × 102 CFU mL−1 (the bactericidal rate was 99.6%) at a concentration of 250 μg mL−1. However, DTPA decreased the growth of E. coli from 3.76 × 104 to 5.60 × 102 CFU mL−1 click here (the bactericidal LGK-974 price rate was 98.5%), and CP252 decreased the

growth of E. coli from 3.76 × 104 to 7.90 × 103 CFU mL−1 (the bactericidal rate was 79.0%) (Fig. 4c). In each case, CP251 was found to be the most effective inhibitor with the Gram-negative bacteria. It is generally accepted that the iron chelators inhibit microbial growth by reducing iron absorption by microorganisms. Based on this concept, the higher the iron-binding constant for the iron chelator, the stronger the predicted antimicrobial activity. However, N,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid, possessing very high affinity for iron (logK=40), was found to be a relatively weak inhibitor of bacteria (Chew et al., 1985), clearly indicating that the composition of the microorganism’s cell wall and the physical nature of the iron chelator also affect the inhibition of bacterial growth. A broad range of structurally different siderophores are produced by Gram-positive and Gram-negative bacteria (Hider & Kong, 2010). Siderophores can extract iron from various other soluble and insoluble iron Selleck C225 compounds, such as

ferric citrate, ferric phosphate, Fe-transferrin, ferritin, iron bound to sugars and glycosides or even from synthetic chelators such as EDTA and nitrilotriacetate. Catecholate siderophores predominate in certain Gram-negative genera, such as Enterobacteria and the genus Vibrio, the reasons for this being manifold, including complex stability, high environmental pH and a weak capability for nitrogen metabolism (Winkelmann, 2002). The Gram-positive Streptomycetes produces hydroxamate-type ferrioxamines and the ascomycetous and basidiomycetous fungi synthesize ester- and peptide-containing hydroxamate siderophores that are acid-stable and well-suited for environmental iron solubilization. Both the Streptomycetes and fungi show a versatile nitrogen metabolism with active N-oxygenases (Winkelmann, 2002). Because of structurally different siderophores and different cell wall types, it can be expected that iron(III)-selective chelators will have a differential influence on a range of bacteria. Of the three iron(III)-selective chelators investigated, CP251 was found to possess the strongest antimicrobial activity, followed by DTPA and CP252.

In conclusion, our data suggest that, in the setting of patients

In conclusion, our data suggest that, in the setting of patients who are kept on NNRTI-based, virologically failing regimens, the rate of accumulation of NNRTI mutations is 0.8 mutations/year on average (>3-fold faster than the rate at which TAMs accumulate) and even faster in the first 6 months after failure. Patients who experienced virological failure with NNRTI resistance

and who have a history of long exposure to nevirapine might gain AZD8055 greater benefits from switching to etravirine than those with long previous exposure to efavirenz. Funding: Primary support for EuroSIDA is provided by the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), 5th Framework (QLK2-2000-00773), 6th Framework (LSHP-CT-2006-018632) and 7th Framework (FP7/2007-2013, EuroCoord n° 260694) programmes. Current support also

includes unrestricted grants from Gilead, Pfizer, Bristol-Myers Squibb and Merck and Co. The participation of centres in Switzerland was supported Epacadostat order by The Swiss National Science Foundation (Grant 108787). Conflicts of interest: None of the authors has any financial or personal relationships with people or organizations that could inappropriately influence this work, although most members of the group have, at some stage in the past, received funding from a variety of pharmaceutical companies for research, travel, speaking engagements or consultancies. “
“Symptomatic hyperlactataemia and lactic acidosis (SHLA) are potentially Tryptophan synthase life-threatening complications associated with stavudine (d4T), an antiretroviral therapy (ART) drug widely used in developing countries. Cases comprised all symptomatic patients with

measured lactates ≥5 mmol/L referred to a South African hospital between August 2003 and November 2005. Matched controls were selected according to facility and duration on ART. Seventy-one cases and 142 controls were included in the study. The majority of cases presented between 6 and 18 months on ART. Female sex [adjusted odds ratio (AOR) 23.4; 95% confidence interval (CI) 4.0–136.6], a baseline weight between 60 and 75 kg (AOR 4.5; 95% CI 1.4–14.1) or, in particular, ≥75 kg (AOR 19.4; 95% CI 4.1–82.5) at ART initiation and gaining ≥6 kg in the first 3 months on therapy (AOR 3.5; 95% CI 1.3–9.5) were independent risk factors identifying patients who may subsequently develop SHLA. Weight loss of ≥2 kg (AOR 6.1; 95% CI 2.0–18.3), a rise in alanine aminotransferase (ALT) ≥10 U/L (AOR 3.1; 95% CI 1.1–8.9), the presence of at least one of three major symptoms (vomiting, nausea and abdominal pains) of SHLA (AOR 12.6; 95% CI 3.3–47.2) and peripheral neuropathy (AOR 3.4; 95% CI 1.1–9.8) were the clinical parameters that were most able to identify patients with early manifestations of SHLA. This is the first case–control study for SHLA in Southern Africa. Given these findings, we advise that stavudine is avoided in overweight women.

This occurred when travelers recorded that more doses of

This occurred when travelers recorded that more doses of

the antimalarial treatment had been taken than had been prescribed by the investigator. It was not possible to go back to the traveler to obtain the reasons for this. Of 252 travelers consented into the study, 251 completed the pre-travel questionnaire (intention-to-treat). Of these, 185 completed the pre- and post-travel questionnaires and these make up the total analyzed sample. No differences of note were seen between the characteristics of those who completed both questionnaires and those who only completed the pre-travel questionnaire. The number of travelers taking each of the medications together with their age and sex Palbociclib are shown in Table 1. The distribution of males and females between the groups was similar, but there were statistically significant differences in mean age, with travelers in the Mfl and At+Pro groups tending to selleck chemical be older than in the Dxy group. The reasons for travel were identified as: business 28%, holiday 59%, visit friends/relatives 8%, and other 5%. The median time of travel was 14 days (inter-quartile range: 9–20 d). Thirty-six percent of the travelers had previously taken one or more of the antimalarials being studied. Adherence analyzed

as the number of tablets reported as taken (as a percentage of prescribed), both overall, which includes pre-, during, and post-travel, (primary end point) and for each period separately are shown in Table 2. Statistically significant differences (at the 5% level) in median percentage adherence were seen between the At+Pro and Dxy groups for overall and post-travel Thiamet G adherence, with travelers taking At+Pro having higher levels of adherence. Median percentage adherence in the Mfl group was numerically lower than for either At+Pro or Dxy overall, pre-, and during travel, and numerically lower than for At+Pro post-travel. Adherence analyzed as the proportion of travelers, who reported taking all their medication from the categorical adherence

scale, is shown in Table 3. A higher percentage of travelers in the At+Pro group compared with the Dxy group stated that they took all their medication overall, during, and post-travel, with statistical significance for overall and post-travel. Categorical adherence in the Mfl group was numerically similar or better than for At+Pro at all stages of travel. Calculating odds ratios, travelers taking At+Pro were 2.59 times more likely to take all post-travel medication compared with Dxy (95% CI 1.27–5.26, p = 0.008) and 2.6 times more likely to take ≥80% of post-travel medication (95% CI 1.29–5.25, p = 0.007). Characteristics such as age or sex did not appear to influence whether travelers reported taking at least 80% or less than 80% of prescribed medication. Factors considered highly important for their choice of antimalarial by travelers completing the pre-travel questionnaire and investigators are shown in Figure 1.

, 2010) and activated sludge performance (Straub, 2009; testing l

, 2010) and activated sludge performance (Straub, 2009; testing limited to COD removal only). The positioning of the high OC-only dosing period in the middle of the pandemic scenario (i.e. dosing of OC and antibiotics) meant that we were not able to completely differentiate the causes of the perturbation to community structure and function; however, it is clear from this study that WWTPs may experience reduced

efficiency during an influenza pandemic owing to the high concentrations of bioactive pharmaceuticals, such as antivirals and antibiotics. The SBR chosen for this study had a relatively long history of stable EBPR performance (>6 months). EBPR failure has previously been shown to occur as a result of competition with glycogen-accumulating organisms (Bond et al., 1999) and from bacteriophage infection (Barr et al., 2010; Barr SD-208 ic50 et al., 2010); hence, the loss in reactor function in this study might not be due to pharmaceutical exposure. However, as quantitative FISH analyses did not demonstrate a decrease in the relative abundance of Candidatus‘Accumulibacter phosphatis’, as would be expected if bacterial competition or bacteriophage predation was to blame, it was concluded that pharmaceutical exposure was the more likely cause. As the SBR was operated as a granular (rather than floccular) sludge, it remains untested whether floccular sludge

would respond differently to such exposure. Granular sludge systems do have some operational differences to floccular systems, such as longer sludge ages, higher mixed liquor SS and lower available surface RGFP966 datasheet all area, all of which might affect sludge–pharmaceutical interactions. It was only after dosing high concentrations of antibiotics and OC that effects on EBPR performance were

noticed. Therefore, it may be that it is only under severe pandemic scenarios that disruption to WWTPs is of concern. Nonetheless, this research highlights the reality of this chemical risk to WWTP function and the need for additional mixed-pharmaceutical dosing studies in WWTP systems. These will be important for optimizing WWTP operation to contend with threats to WWTP function, and for understanding and modelling the release of pharmaceuticals into the environment. We thank F. Hoffman-La Roche Ltd for the kind donation of OC and Michael Poole for assistance with Fig. S1. This work was funded by a UQ New Staff Research Start-up Grant awarded to F.R.S. and the Natural Environment Research Council – Knowledge Transfer Initiative (PREPARE) contract no. NE/F009216/1 awarded to A.C.S. We thank two anonymous reviewers for their comments on the text. Fig. S1. Simulated effluent OC concentrations based on measured influent OC concentrations and four SBR draw and fill occurrences per day, each with a volumetric exchange ratio of 1:4, and assuming no sorption or biological transformation (i.e.