A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.

Intellectual disability (ID) is associated with an increased risk of developing psychiatric disorders, suggesting a common underlying genetic factor. Importantly, altered signaling and/or expression of regulator of G protein signaling 6 (RGS6) is associated with ID and numerous psychiatric disorders. RGS6 is highly conserved and undergoes complex alternative mRNA splicing producing ~36 protein isoforms with high sequence similarity historically necessitating a global approach in functional studies. However, our recent analysis in mice revealed RGS6 is most highly expressed in CNS with RGS6L(+GGL) isoforms predominating. A previously reported genetic variant in intron 17 of RGS6 (c.1369-1G>C), associated with ID, may provide further clues into RGS6L(+GGL) isoform functional delineation. This variant was predicted to alter a highly conserved canonical 3' acceptor site creating an alternative branch point within exon 18 (included in a subset of RGS6L(+GGL) transcripts) and a frameshift forming an early stop codon. We previously identified this alternative splice site and demonstrated its use generates RGS6Lζ(+GGL) isoforms. Here, we show that the c.1369-1G>C variant disrupts the canonical, preferred (>90%) intron 17 splice site and leads to the exclusive use of the alternate exon 18 splice site, inducing disproportionate expression of a subset of isoforms, particularly RGS6Lζ(+GGL). Furthermore, RGS6 global knockout mice do not exhibit ID. Thus, ID caused by the c.1369-1G>C variant likely results from altered RGS6 isoform expression, rather than RGS6 isoform loss. In summary, these studies highlight the importance of proper RGS6 splicing and identify a previously unrecognized role of G protein signaling in ID.

Ground-Based Mobile Measurements to Track Urban Methane Emissions from Natural Gas in 12 Cities across Eight Countries.

To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.

Capsular inflammation after immediate breast reconstruction - Gene expression patterns and inflammatory cell infiltration in irradiated and non-irradiated breasts.

BACKGROUND: Capsular contracture following post-mastectomy radiotherapy (PMRT) is commonly seen in patients undergoing implant-based immediate breast reconstruction (IBR). Further understanding of the underlying biology is needed for the development of preventive or therapeutic strategies. Therefore, we conducted a comparative study of gene expression patterns in capsular tissue from breast cancer patients who had received versus those who had not received PMRT after implant-based IBR. METHODS: Biopsies from irradiated and healthy non-irradiated capsular tissue were harvested during implant exchange following IBR. Biopsies from irradiated (n = 13) and non-irradiated (n = 12) capsules were compared using Affymetrix microarrays to identify the most differentially regulated genes. Further analysis using immunohistochemistry was performed in a subset of materials to compare the presence of T cells, B cells, and macrophages. RESULTS: Enrichment testing using Gene Ontology (GO) analysis revealed that the 227 most differentially expressed genes were mainly involved in an inflammatory response. Twenty-one GO biological processes were identified [p < 0.05, false discovery rate (FDR) < 5%], several with B-cell-associated inflammation. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis identified macrophages as the most common inflammatory cell type in both groups, further supported by immunostaining of CD68. Radiation remarkably increased B-cell infiltration in the capsular region of biopsies, as quantified by immunostaining of CD20 (p = 0.016). CONCLUSIONS: Transcript analysis and immunohistochemistry revealed inflammatory responses in capsular biopsies regardless of radiotherapy. However, the radiation response specifically involved B-cell-associated inflammatory responses.

Modeling Global Carbon Costs of Plant Nitrogen and Phosphorus Acquisition.

Most Earth system models (ESMs) do not explicitly represent the carbon (C) costs of plant nutrient acquisition, which leads to uncertainty in predictions of the current and future constraints to the land C sink. We integrate a plant productivity-optimizing nitrogen (N) and phosphorus (P) acquisition model (fixation & uptake of nutrients, FUN) into the energy exascale Earth system (E3SM) land model (ELM). Global plant N and P uptake are dynamically simulated by ELM-FUN based on the C costs of nutrient acquisition from mycorrhizae, direct root uptake, retranslocation from senescing leaves, and biological N fixation. We benchmarked ELM-FUN with three classes of products: ILAMB, a remotely sensed nutrient limitation product, and CMIP6 models; we found significant improvements in C cycle variables, although the lack of more observed nutrient data prevents a comprehensive level of benchmarking. Overall, we found N and P co-limitation for 80% of land area, with the remaining 20% being either predominantly N or P limited. Globally, the new model predicts that plants invested 4.1 Pg C yr-1 to acquire 841.8 Tg N yr-1 and 48.1 Tg P yr-1 (1994-2005), leading to significant downregulation of global net primary production (NPP). Global NPP is reduced by 20% with C costs of N and 50% with C costs of NP. Modeled and observed nutrient limitation agreement increases when N and P are considered together (r 2 from 0.73 to 0.83).

Protein Profiling of RGS6, a Pleiotropic Gene Implicated in Numerous Neuropsychiatric Disorders, Reveals Multi-Isoformic Expression and a Novel Brain-Specific Isoform.

A metanalysis identified regulator of G-protein signaling 6 (RGS6) as one of 23 loci with pleiotropic effects on four or more human psychiatric disorders. This finding is significant as it confirms/extends the findings of numerous other studies implicating RGS6 in CNS function and pathology. RGS6 is a highly conserved member of the RGS protein family whose cellular roles are likely affected by mRNA splicing and alternative domain inclusion/exclusion. Indeed, we previously identified multiple RGS6 splice variants predicted to produce 36 distinct protein isoforms containing either long (RGS6L) or short (RGS6S) N-terminal domains, an incomplete or intact GGL domain, and nine alternative C termini. Unfortunately, sequence similarities between the isoforms have made it difficult to confirm their individual existence and/or to determine their unique functions. Here, we developed three RGS6-specific antibodies that recognize all RGS6 protein isoforms (RGS6-fl), the N-terminus of RGS6L isoforms (RGS6-L), and an 18-amino acid alternate C-terminal sequence (RGS6-18). Using these antibodies, we demonstrate that RGS6L(+GGL) isoforms, predominating in both mouse (both sexes) CNS and peripheral tissues, are most highly expressed in the CNS. We further identify three novel RGS6 protein bands that are larger (61, 65, and 69-kDa) than the ubiquitously expressed 53- to 57-kDa RGS6L(+GGL) proteins. Importantly, we show that the 69-kDa protein is a brain-specific dephospho form of the 65-kDa band, the first identified phosphorylated RGS6 isoform. Together, these data begin to define the functional significance behind the complexity of RGS6 gene processing and further clarifies RGS6's physiological roles by resolving tissue-specific RGS6 protein expression.

Laparoscopic vs open surgery during the COVID-19 pandemic: what are the risks?

INTRODUCTION: The initial intercollegiate surgical guidance from the UK during the COVID-19 pandemic resulted in significant changes to practice. Avoidance of laparoscopy was recommended, to reduce aerosol generation and risk of virus transmission. Evidence on the safety profile of laparoscopy during the pandemic is lacking. This study compares patient outcomes and risk to staff from laparoscopic and open gastrointestinal operations during the COVID-19 pandemic. METHODS: Single-centre retrospective study of gastrointestinal operations performed during the peak of the COVID-19 pandemic. Demographic, comorbidity, perioperative and survival data were collected from electronic medical records and supplemented with patient symptoms reported at telephone follow up. Outcomes assessed were: patient mortality, illness among staff, patient COVID-19 rates, length of hospital stay and postdischarge symptomatology. RESULTS: A total of 73 patients with median age of 56 years were included; 55 (75%) and 18 (25%) underwent laparoscopic and open surgery, respectively. All-cause mortality was 5% (4/73), was related to COVID-19 in all cases, with no mortality after laparoscopic surgery. A total of 14 staff members developed COVID-19 symptoms within 2 weeks, with no significant difference between laparoscopic and open surgery (10 vs 4; p=0.331). Median length of stay was shorter in the laparoscopic versus the open group (4.5 vs 9.9 days; p=0.011), and postdischarge symptomatology across 15 symptoms was similar between groups (p=0.135-0.814). CONCLUSIONS: With appropriate protective measures, laparoscopic surgery is safe for patients and staff during the COVID-19 pandemic. The laparoscopic approach maintains an advantage of shorter length of hospital stay compared with open surgery.

Recent Developments in Species Sensitivity Distribution Modeling.

The species sensitivity distribution (SSD) is a statistical approach that is used to estimate either the concentration of a chemical that is hazardous to no more than x% of all species (the HCx) or the proportion of species potentially affected by a given concentration of a chemical. Despite a significant body of published research and critical reviews over the past 20 yr aimed at improving the methodology, the fundamentals remain unchanged. Although there have been some recent suggestions for improvements to SSD methods in the literature, in general, few of these suggestions have been formally adopted. Furthermore, critics of the approach can rightly point to the fact that differences in technical implementation can lead to marked differences in results, thereby undermining confidence in SSD approaches. Despite the limitations, SSDs remain a practical tool and, until a demonstrably better inferential framework is available, developments and enhancements to conventional SSD practice will and should continue. We therefore believe the time has come for the scientific community to decide how it wants SSD methods to evolve. The present study summarizes the current status of, and elaborates on several recent developments for, SSD methods, specifically, model averaging, multimodality, and software development. We also consider future directions with respect to the use of SSDs, with the ultimate aim of helping to facilitate greater international collaboration and, potentially, greater harmonization of SSD methods. Environ Toxicol Chem 2021;40:293-308. © 2020 SETAC.

The evolution of multicellular complexity: the role of relatedness and environmental constraints.

A major challenge in evolutionary biology has been to explain the variation in multicellularity across the many independently evolved multicellular lineages, from slime moulds to vertebrates. Social evolution theory has highlighted the key role of relatedness in determining multicellular complexity and obligateness; however, there is a need to extend this to a broader perspective incorporating the role of the environment. In this paper, we formally test Bonner's 1998 hypothesis that the environment is crucial in determining the course of multicellular evolution, with aggregative multicellularity evolving more frequently on land and clonal multicellularity more frequently in water. Using a combination of scaling theory and phylogenetic comparative analyses, we describe multicellular organizational complexity across 139 species spanning 14 independent transitions to multicellularity and investigate the role of the environment in determining multicellular group formation and in imposing constraints on multicellular evolution. Our results, showing that the physical environment has impacted the way in which multicellular groups form, highlight that environmental conditions might have affected the major evolutionary transition to obligate multicellularity.

The Unmet Needs of Stroke Survivors and Stroke Caregivers: A Systematic Narrative Review.

INTRODUCTION: Facilitating stroke survivors and their caregivers to lead a fulfilling life after stroke requires service providers to think about their different needs. Poor post stroke care may lead to unmet needs in stroke survivors and stroke caregivers. This may compromise them in leading their lives optimally after stroke. OBJECTIVES & METHODOLOGY: This systematic narrative review examines articles published from 1990 to 2017, generated from Ovid, MEDLINE, CINAHL, and PubMed. The search was also supplemented by an examination of reference lists for related articles via Scopus. We included 105 articles. FINDINGS: We found that the type of unmet needs in stroke survivors and the contributing factors were substantially different from their caregivers. The unmet needs in stroke survivors ranged from health-related needs to re-integration into the community; while the unmet needs in stroke caregivers ranged from information needs to support in caring for the stroke survivors and caring for themselves. Additionally, the unmet needs in both groups were associated with different factors. CONCLUSION: More research is required to understand the unmet needs of stroke survivors and stroke caregivers to improve the overall post-stroke care services.

Eccentric Taylor spatial frame placement for the correction of femoral fracture deformity: a novel technique.

The treatment of post-traumatic femoral deformity with circular frames can be difficult both for the patient and for the surgeon. Patients frequently suffer from residual knee stiffness, and the cumbersome location of the frame can even result in psychiatric problems such as depression and anxiety during their treatment. Here we describe a novel technique of constructing the Taylor spatial frame (TSF) eccentrically from the femur to allow the same level of comfort as a monolateral external fixator, while applying trigonometric principles to successfully retain the utility of the TSF prescription software. Deformity correction and fracture compression can therefore still be achieved in a controlled and predictable manner on an outpatient basis.

Demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma: a UK population study.

OBJECTIVE: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma. DESIGN: A retrospective national population-based study. SETTING: UK 1995-2015. POPULATION: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield. METHODS: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics. MAIN OUTCOMES: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group. RESULTS: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%. CONCLUSIONS: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age. TWEETABLE ABSTRACT: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence.

Lung metastases in low-risk gestational trophoblastic neoplasia: a retrospective cohort study.

OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.

Virtual arthroplasty follow-up: five-year data from a district general hospital.

INTRODUCTION: Follow-up after hip and knee arthroplasty is advocated to identify asymptomatic loosening and improve patient satisfaction. There are, however, financial and time implications associated with regular clinic appointments. Assessment through virtual means has been suggested as an alternative. MATERIALS AND METHODS: At the West Suffolk Hospital, following arthroplasty surgery of the lower limb, patients are followed-up via a questionnaire at one and five years postoperatively, then subsequently at five-yearly intervals. Patients are recalled based on the outcome of these assessments. Using a locally compiled data base we identified all patients reviewed between 2011 and 2015 using this virtual assessment process and examined their outcomes. RESULTS: During the five years of follow-up, 5,380 patients were eligible for assessment. Compliance varied from 77% follow up for hips and 83% for knees. Ten patients were recalled following total hip replacement, eight for x-ray changes and one for a poor satisfaction score. Five went on to undergo revision surgery. Some 56 recalls to clinic following knee arthroplasty were seen; 42 due to a poor Oxford Knee Score, 6 with associated x-ray abnormalities and 6 isolated abnormal x-rays. Five subsequently underwent revision surgery; 30 (54%) were discharged after initial review and 18 (32%) were referred to different subspecialties.As a result of the virtual review process, 4,219 clinic appointments were avoided, with no documented admissions as a result of a missed complication from virtual review. DISCUSSION: A virtual arthroplasty clinic significantly reduces the number of patients attending regular follow-up clinics, without compromising safe practice.

Randomized, Placebo Controlled Trial of NPT088, A Phage-Derived, Amyloid-Targeted Treatment for Alzheimer's Disease.

The engineered fusion protein NPT088 targets amyloid in vitro and in animal models of Alzheimer's disease. Previous studies showed that NPT088 treatment reduced ß-amyloid plaque and tau aggregate loads in mouse disease models. Here, we present the results from an initial clinical study of NPT088 in patients with mild to moderate Alzheimer's disease. Patients were treated with 4 dose levels of NPT088 for 6 months to evaluate its safety and tolerability. Exploratory measurements included measurement of change in ß-amyloid plaque and tau burden utilizing Positron Emission Tomography imaging as well as measures of Alzheimer's disease symptoms. At endpoint NPT088 was generally safe and well-tolerated with the most prominent finding being infusion reactions in a minority of patients. No effect of NPT088 on brain plaques, tau aggregates or Alzheimer's disease symptoms was observed.

Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life.

PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.

Multicellular group formation in Saccharomyces cerevisiae.

Understanding how and why cells cooperate to form multicellular organisms is a central aim of evolutionary biology. Multicellular groups can form through clonal development (where daughter cells stick to mother cells after division) or by aggregation (where cells aggregate to form groups). These different ways of forming groups directly affect relatedness between individual cells, which in turn can influence the degree of cooperation and conflict within the multicellular group. It is hard to study the evolution of multicellularity by focusing only on obligately multicellular organisms, like complex animals and plants, because the factors that favour multicellular cooperation cannot be disentangled, as cells cannot survive and reproduce independently. We support the use of Saccharomyces cerevisiae as an ideal model for studying the very first stages of the evolution of multicellularity. This is because it can form multicellular groups both clonally and through aggregation and uses a family of proteins called 'flocculins' that determine the way in which groups form, making it particularly amenable to laboratory experiments. We briefly review current knowledge about multicellularity in S. cerevisiae and then propose a framework for making predictions about the evolution of multicellular phenotypes in yeast based on social evolution theory. We finish by explaining how S. cerevisiae is a particularly useful experimental model for the analysis of open questions concerning multicellularity.

Importance of 2,4,6-Trichloroanisole (TCA) as an odorant in the emissions from anaerobically stabilized dewatered biosolids.

Odours from stabilized biosolids after anaerobic digestion of wastewater sludge can cause local community impact. Apart from the well-known odorants such as sulfur compounds, contributions from other volatile organic compounds (VOCs) to nuisance odours is limited. The presence of compounds with low odour detection thresholds (ODTs) at low concentrations, can present challenges for analytical identification. Thirty-six biosolids samples were taken after anaerobic stabilisation and dewatering at a wastewater treatment plant, Sydney, Australia. Biosolid cake samples were stored outside in loosely covered trays under aerobic conditions, however without interactions with soil microorganisms as it would be in reality. All biosolids cake samples were analysed over a period of 35 days. Emissions were collected onto Tenax TA sorbent tubes using a U.S. EPA flux hood method at storage days 1, 3, 7, 10, 14, 21 and 35. Gas chromatography (GC) coupled with mass spectrometer detector (MSD) and an olfactory detection port (ODP) was used to identify a musty/moldy/earthy type odorant in the biosolids emissions as 2,4,6-trichloroanisole (TCA). Measured odour intensities, classified on a scale from 1 to 4, and odour characters were specified by three ODP assessors. TCA was identified in all biosolid cake emissions. The measured odour intensities of the TCA did not significantly alter as the biosolids were aged, however varied between biosolids cakes. Due to its odour intensity, 85% frequency of detection and its low ODT, which is orders of magnitudes lower than sulfur compounds, TCA should be considered as a potential odorant of concern in biosolids emissions.

Establishing and developing a Teenage and Young Adult dermatology clinic with embedded specialist psychological support.

Skin conditions are common in adolescence and impart considerable psychological burden. The Department of Health has identified the specialized needs of adolescents transitioning from paediatric to adult services as a priority, yet there are few dedicated transitional clinics in the UK providing appropriate psychosocial support. We have established a monthly Teenage and Young Adult (TYA) dermatology clinic dedicated to managing teenagers and young adults with skin disease alongside open-access psychological support. Demographic data and Teenagers' Quality of Life Index (T-QoL) measures were recorded for all patients in 2016. To evaluate patient experience, two online surveys were conducted. Statistically significant improvements in the T-QoL were recorded for patients with the most common skin condition (eczema) attending for repeat assessment by the psychologist. Patients reported high satisfaction rates in both patient experience surveys. These results demonstrate that specialized adolescent care both is well received and can improve outcomes for these patients.

Nitrogen removal from coke making wastewater through a pre-denitrification activated sludge process.

Under the Industrial Emissions Directive (IED), coke production wastewater must be treated to produce an effluent characterised by a total nitrogen (TN) <50 mg/L. An anoxic-aerobic activated sludge pilot-plant (1 m3) fed with coke production wastewater was used to investigate the optimal operational requirements to achieve such an effluent. The loading rates applied to the pilot-plant varied between 0.198-0.418 kg COD/m3.day and 0.029-0.081 kg TN/m3.day, respectively. The ammonia (NH4+-N) removals were maintained at 96%, after alkalinity addition. Under all conditions, phenol and SCN- remained stable at 96% and 100%, respectively with both being utilised as carbon sources during denitrification. The obtained results showed that influent soluble chemical oxygen demand (sCOD) to TN ratio of should be maintained at >5.7 to produce an effluent TN <50 mg/L. Furthermore, nitrite accumulation was observed under all conditions indicating a disturbance to the denitrification pathway. Overall, the anoxic-aerobic activated sludge process was shown to be a robust and reliable technology to treat coke making wastewater and achieve the IED requirements. Nevertheless, the influent to the anoxic tank should be monitored to ensure a sCOD:TN ratio >5.7 or, alternately, the addition of an external carbon source should be considered.