[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

[Pathophysiology of inflammation]. / Pathophysiologie der Entzündung.

Inflammation results from activation of the immune system in response to a broad range of different stimuli. The immune system is a highly complex and evolutionary optimized defense system with cellular and humoral components. The course of an inflammatory response is influenced by the immune condition of the host, the virulence e. g. of an infectious agent, and the fine tuning of the local tissue reaction, which may be influenced by individual genetic factors. Immunity is a compromise between insufficient (immunodeficiency) or exaggerated (autoimmunity) immune reactions. The dynamic balance between these two extremes is achieved through stringent T- and B-cell selection in the bone marrow and thymus on the one hand and through "checkpoint control" in peripheral lymphatic tissues. Many tumors have ways to suppress local immune responses and to escape destruction through the immune system (one of the so-called "hallmarks of cancer"). In recent years, different approaches have successfully been able to reverse this local immunosuppression. First clinical trials using these strategies have shown highly promising results indicating that the therapeutic use of the immune system will be a very effective instrument in the arsenal of cancer treatment agents.

Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a promising target for diagnostics and therapy of prostate carcinoma (PCa). Based on the hypothesis that PSMA expression can be modulated by variations in androgen deprivation therapy (ADT), we investigated the binding of a PSMA-directed radiopharmaceutical in vitro in order to get an insight of the interactions between altered premedication and PSMA expression before repetitive PSMA-directed PET/CT for therapy response and targeted therapy implementation. METHODS: The human castration-resistant PCa cell line VCaP (CRPC) was treated with either 1 nmol/L testosterone (T) over 20 passages yielding the androgen-sensitive cell line (revCRPC) or with 5 µmol/L abiraterone acetate (AA) generating the abiraterone-tolerant subtype CRPCAA. In these cell lines, T and AA were varied by either supply or withdrawal of T and AA. PSMA expression of the three cell culture models was detected by Western blot and immunohistochemical staining. For quantitative measurement of tracer uptake, 0.3 nmol/L (68)Ga-labelled PSMA-HBED-CC peptide (100-300 kBq/ml) was added to different treated parallel cultures (n = 9 each). Time-dependent uptake per 10(6) cells of each culture was calculated and evaluated. PSMA mRNA expression was investigated by qPCR. RESULTS: PSMA expression increased dependently on intensified ADT in all three basic cell lines. (68)Ga-PSMA-HBED-CC uptake almost doubled during 3 h in all cell lines (p < 0.01). Compared to the basic cells, pre-incubation with abiraterone for 48 h resulted in a significant increased uptake in CRPC (p < 0.001). In revCRPC, 48-h AA pre-incubation resulted in an eightfold higher uptake after 3 h (p < 0.001). Additional withdrawal of external testosterone increased the uptake up to tenfold (p < 0.01). The increase of PSMA expression upon ADT and AA treatments was confirmed by qPCR and Western blot data. Furthermore, in CRPCAA, 48-h AA withdrawal increased the uptake up to fivefold (p < 0.01). CONCLUSIONS: The investigated three PCa cell culture subtypes represent a serial preclinical model of androgen deprivation therapy as a proxy for clinical situations with differing basal PSMA expression. The uptake of PSMA-binding tracers could be stimulated by therapeutic effective short-term variation in premedication in all stages of ADT response. These complex interactions have to be considered in the interpretation of diagnostic imaging using PSMA ligands as well as in the optimal timing of PSMA-based therapies.

Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by 68Ga-PSMA-positron emission tomography/computerized tomography.

BACKGROUND: The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by (68)Ga-PSMA PET/CT. METHODS: Retrospective analysis of 35 PCa patients underwent (68)Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n = 23) or before primary therapy of high-risk PCa (n = 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS: Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18-30) and 19.5 ng/ml (range 6-90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4-17) and 12 (range 8-29) per patient and the median number of positive lymph nodes was 1 (range 1-2) and 3 (2-3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS: This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by (68)Ga-PSMA PET/CT. The use of (68)Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies.

How reliable is secondary risk stratification with stimulated thyroglobulin in patients with differentiated thyroid carcinoma? Results from a retrospective study.

OBJECTIVE: Primary risk factors in patients with differentiated thyroid carcinoma (DTC) are well established. In our institution, secondary risk stratification has been performed with stimulated Thyroglobulin (sTg; TSH > 30 mIU/l) within six months after primary therapy since 2001. In this study, we evaluated the predictive value of sTg for long-term disease-free survival (DFS). PATIENTS, METHODS: Data of 202 consecutive patients with DTC were analyzed retrospectively. Median follow-up time was 6.4 years (12 months to 16.2 years). Patients were staged according to Union International Contre le Cancer (UICC) criteria. Primary risk stratification was carried out according to European Thyroid Association criteria. Initially, 134 patients (66%) were classified as low-risk and 68 patients (34%) as high-risk. The influence of established risk factors and sTg on DFS was analyzed at three different time points, up to 36 months after initial therapy. RESULTS: In total, 169 (84%) of all patients remained in complete remission after surgery followed by radioiodine-therapy. Six patients (3%) developed tumour recurrence after initial complete remission. Primary risk factors for persistent disease were male sex, follicular or oncocytic tumour, primary tumour > 4 cm in diameter, initial lymph node involvement, initial metastatic disease and microscopic or macroscopic residual tumor. sTg ≤ 0.3 ng/ml measured within six months after initial therapy was a highly significant predictor (p ≤ 0.001) for lasting DFS, 99% of patients with sTg ≤ 0.3 ng/ml were in complete remission 36 months after initial therapy. CONCLUSIONS: A stimulated Tg ≤ 0.3 ng/ml within six months after initial therapy is a reliable predictor for long-term disease-free survival independent of primary risk stratification.

Metastatic recurrence after complete resection of colorectal liver metastases: impact of surgery and chemotherapy on survival.

PURPOSE: Surgery is the standard of care for resectable colorectal liver metastases (CRC-LM). Unfortunately, 60% of patients develop secondary metastatic recurrence (SMR) after R0-resection of CRC-LM. We investigated the impact of surgical re-intervention and chemotherapy (Ctx) on survival in a consecutive series of patients with SMR. METHODS: From 01/2001 to 11/2011, 104 out of 178 consecutive patients with R0-resection of CRC-LM developed SMR and were evaluated. The impact of surgical and Ctx re-interventions on recurrence free (RFS) and cancer-specific survival (CSS) was analyzed. Median follow-up was 28.0 (95%CI: 19.4-37.4) months. RESULTS: SMR occurred in 81 patients at a single site (49× liver, 18× lung, 14× other) and in 23 patients at multiple sites. Forty-two patients were scheduled for primary surgery. Fifty-three patients were classified as non-resectable and treated with median 5.0 [IQR, 3.0-10.0] cycles of Ctx, combined with an EGFR/VEGF-antibody in 27 patients. Nine patients received best supportive care only. R0/R1 resection could be achieved in 35 patients primarily and even in 8 patients secondarily after Ctx. Surgical morbidity and mortality were 16 and 0%, respectively. The 5-year RFS rates for patients with R0 versus R1-resection were 22 and 24% (p = 0.948). The 5-year CSS rate for R0/R1-resected patients was 38% versus 10% for those patients treated by Ctx alone (p < 0.001). CONCLUSION: In SMR, surgical re-intervention is feasible and safe in a remarkable number of patients and offers significantly longer CSS compared to patients without resection.

Patients with autoimmune thyroiditis. Prevalence of benign lymphadenopathy.

UNLABELLED: The prevalence of cervical lymphadenopathy in autoimmune thyroiditis (AIT) patients is actually unknown. The aim of the study was the detailed retrospective evaluation of 6 index-patients with lymphadenopathy in Robbins level VI and a prospective study with high resolution ultrasound of lymphadenopathy in AIT patients compared with controls in all compartments of the neck, accessible to sonographic evaluation. PATIENTS, METHODS: The retrospective study comprises six patients with AIT, evaluated for enlarged Robbins level VI-LN. We report the findings of fine-needle aspiration Cytology, clonal analysis, histology, and serological testing. The prospective study evaluated the prevalence of lymphadenopathy in 49 consecutive patients with AIT (group 1) and 49 consecutive patients with normal thyroids or nontoxic goiter (group 2). RESULTS: In the retrospective study, cytology of paratracheal LN revealed reactive lymphoid hyperplasia in 5/6 of the cases and a centroblastic lymphoma in one patient. The presence of monoclonal lymphatic cells was excluded in 5/6 patients and proven in 1/6 patients. Actual viral-infections were ruled out. In the prospective study AIT-patients showed significantly more enlarged LN in Robbins level II-IV and VI compared to controls. We found no correlation between lymphadenopathy, age, thyroid volume and nodularity, or autoantibody levels. During follow-up in 34 group 1-patients, lymphadenopathy remained stable in 28 patients, and decreased in 6 patients. CONCLUSION: Lymphadenopathy in Robbins level II-IV and VI is common in AIT-patients and most probably related to the autoimmune process.

Bilobar spreading of colorectal liver metastases does not significantly affect survival after R0 resection in the era of interdisciplinary multimodal treatment.

PURPOSE: Bilobar colorectal liver metastases (CRLM) are often considered incurable or associated with poor prognosis even after R0 resection. In this single-center study, we evaluate the impact of CRLM spreading on recurrence-free survival (RFS) and cancer-specific overall survival (CSS) after R0 resection of CRLM with respect to multimodal treatment strategies including perioperative chemotherapy and multistep resections. METHODS: Between January 2001 and December 2010, R0 resection could be achieved in 70 patients with bilobar and 100 with unilobar CRLM. Extent of disease, perioperative chemotherapy, surgical procedures, adjuvant treatment, histopathological workup, RFS, and CSS were compared between both cohorts. RESULTS: Forty-six (66 %) patients with bilobar and 26 (26 %) patients with unilobar CRLM received preoperative chemotherapy (p < 0.001). For bilobar CRLM, more extended and multistep resection including portal vein occlusion were performed (29 % versus 3 %; p < 0.001). Morbidity (39 % versus 28 %, p = 0.183) and mortality (1 % versus 3 %, p = 0.644) rates were comparable in both patients' cohorts. Postoperative therapy was applied in adjuvant intent to 42 (60 %) versus 51 (51 %) patients (p = 0.275). The 5-year RFS and CSS rates were 24 % versus 31 % (p = 0.169) and 42 % versus 55 % (p = 0.131), respectively. CONCLUSIONS: To our single-center experience, there is no significant effect of CRLM spreading (bilobar versus unilobar) on RFS and CSS rates. Bilobar CRLM are more likely to require extended multimodal efforts to achieve R0 resection.

[(68)Ga-labeled peptides for clinical trials - production according to the German Drug Act: the Göttingen experience]. / (68)Ga-markierte Peptide für klinische Studien. Herstellung gemäß Arzneimittelgesetz: Göttinger Erfahrungen.

The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials. AIM, METHODS: As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission. RESULTS: During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection. CONCLUSIONS: The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.

Targeting NCA-95 and other granulocyte antigens and receptors with radiolabeled monoclonal antibodies (Mabs).

During the last decade considerable effort has been made in the research for in vivo techniques of labeling neutrophils with peptides, labeled cytokines and (99m)Tc-labeled antigranulocyte monoclonal antibodies (AG-Mabs). In general the advantage of in vivo labeling is the simplicity of this approach compared with in vivo techniques. Three of these AG-Mabs have been evaluated in clinical studies: Besilesomab (Scintimun®), Sulesomab (Leucoscan®) and Fanolesomab (Leu-Tech®). White blood cells (WBCs) radiolabeled with AG-Mabs do not show the same behaviour as in vivo labeled white blood cells. Especially (99m)Tc-Sulesomab and (99m)Tc-Besilesomab image infectious foci mainly by non-specific extravasation with secondary binding to postmigratory leukocytes already present at the site of infection.

FDG-PET in patients with fever of unknown origin: the importance of diagnosing large vessel vasculitis.

This review analyzes the impact of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) in the diagnostic work-up of classic fever of unknown origin (FUO) according to the criteria first proposed by Petersorf in 1961 and later modified by Durack et al. in 1991. Algorithms currently used in this diagnostic process are not strictly evidence based up to now. FDG accumulates in malignant tissues, but also in inflammatory cells by the overexpression of facultative glucose transporter-isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic enzymes. Therefore, this technique covers a broad spectrum of possible etiologies for FUO. Once imaged, these lesions can be further investigated by other (e.g. invasive) and more specific methods. Until now, four prospective studies using FDG-PET in patients with classic FUO, encompassing 167 patients in total are published. Three retrospective studies with 125 patients are also available. These studies are discussed and weighted according to the control of selection-bias that was performed. An interstudy-bias may also be present resulting from a considerable variability in causes of FUO. A low number of diagnostic scans in a study may sometimes be related to a high rate of fevers caused by miscellaneous disorders or to a high rate of undiagnosed patients. In these disease categories, focal pathologies that can be imaged with FDG-PET, are rare. A high number of diagnostic scans is always related to a high prevalence of patients with medium- and large-vessel vasculitis. Available data indicate that FDG-PET has the potential to play an important role as a second line procedure in the management of about 1/3 of patients with classic FUO. It is expected that hybrid imaging (PET/computed tomography [CT]; PET/magnetic resonance imaging [MRI]) will improve the diagnostic impact of FDG-PET further, but prospective data about the value of this methods are currently not available. The question as to how these new techniques can be implemented into an evidence based diagnostic algorithm, can only be resolved within a multidisciplinary setting, avoiding both selection- and interstudy-bias whenever possible.

Evaluation of oxygen transfer efficiency under process conditions using the dynamic off-gas method.

The off-gas method can be used to investigate standard oxygen transfer efficiencies under process conditions (alphaSOTE) over the operating life of an aeration system. A method to evaluate alphaSOTE is described in detail by US and German standards. The standards, however, do not describe how to evaluate dynamic changes in aSOTE over a day, which can be useful to uncover problems and unfavourable process conditions. Based on over three years experience gained in off-gas testing in Berlin wastewater treatment plants (WWTPs) under operating conditions, a method to evaluate and interpret the dynamic changes in oxygen transfer is presented. The application of the dynamic off-gas method brings important additional information, which can be used to increase operational efficiency of the aeration basin and to increase process reliability, with a relatively small increase in effort. This paper shows how to perform dynamic measurements under process conditions. Some results of such measurements under dynamic process conditions, performed in a Berlin WWTP, are discussed.

[A 22 year old woman with fever, night sweats, weight loss and hepatomegaly]. / 22-jährige Frau mit Fieber, Nachtschweiss, Gewichtsverlust und Hepatomegalie.

A 22 year old female patient presented with fever, night sweats, weight loss and hepatomegaly associated with elevated inflammatory parameters and liver enzymes. Computer tomography revealed a mass located between the inferior vena cava and the psoas muscle as well as enlarged celiac, retroperitoneal and retrocaval lymph nodes. Biopsies of the retrocaval mass led to the diagnosis of retroperitoneal fibrosis. Within a few days of treatment with corticosteroids clinical presentation improved and imaging studies detected complete regression of the retrocaval mass after 6 months.

[Improvement of tomographic reconstruction in bone SPECT]. / Optimierung der tomographischen Rekonstruktion in der Skelett-SPECT.

AIM: The comparison between iterative reconstruction and filtered backprojection in the reconstruction of bone SPECT in the diagnosis of skeletal metastases. PATIENTS, METHODS: 47 consecutive patients (vertebral segments: n = 435), with suspected malignancy of the vertebral column, were examined by bone scintigraphy and MRI (maximal interval between the two procedures +/- 5 weeks). The SPECT-data were reconstructed with an iterative algorithm (ISA) and with filtered backprojection. We defined semiquantitative criteria in order to assess the quality of the tomograms. Conventional reconstruction was performed both by a Wiener-filter and a low-pass-filter. Iterative reconstruction was performed by the ISA algorithm. The clinical evaluation of the different reconstruction algorithms was performed by MRI as the gold-standard. RESULTS: Sensitivity (%): 87.3 (ISA), 86.4 (low-pass), 79.7 (Wiener); specificity (%): 95.3 (ISA), 95 (low-pass), 85.4 (Wiener). The sensitivity of iterative reconstructed SPECT and low-pass reconstructed SPECT was significantly higher (p < 0.05) compared with the sensitivity of SPECT reconstructed by the Wiener-filter. The specificity of iterative reconstruction ISA and low-pass-filter reconstructed SPECT were significantly higher compared with the SPECT data reconstructed by the Wiener-filter. ISA was significantly superior to the Wiener-SPECT relating to all criteria of quality. Iterative reconstruction was significantly superior to the low-pass-SPECT relating to 2 of 3 criteria. In addition the Wiener-SPECT was significantly inferior to the low-pass-SPECT regarding to 2 of 3 criteria. CONCLUSION: In our series the iterative algorithm ISA was the method of choice in the reconstruction of bone SPECT data. In comparison with conventional algorithms ISA offers a significantly higher quality of the tomograms and yields a high diagnostic accuracy.

Evaluation of ceramic and membrane diffusers under operating conditions with the dynamic offgas method.

The aeration systems of two full-scale, activated-sludge basins were compared during a period of three years, under the same operating conditions, using dynamic offgas testing. Only the material of the diffuser was different (membrane versus ceramic-tube diffusers). The investigation has shown that, although the membrane diffusers have higher initial standard-oxygen-transfer efficiency (alphaSOTE) and standard-aeration efficiency (alphaSAE), these decreased over time, while the alphaSAE of the ceramic diffusers started lower, but increased slightly over the whole period. A cost comparison makes clear how important it is to evaluate the aeration system under process conditions. The operating costs were the dominant factor (approximately 10x higher than capital costs), and operating costs were approximately 20% higher for membrane versus ceramic diffusers. The poor performance of the membrane-tube diffusers under process conditions could be explained on the basis of the actual alphaAE values in the basin, not the standardized values.

Expression of the sodium iodide symporter in differentiated thyroid cancer: clinical evidence.

AIM: Molecular analysis of the expression of the sodium iodide symporter (NIS) in 32 patients with differentiated thyroid cancer (DTC) and correlation with scintigraphic findings ((131)I,(123)I) in 19 (59.4%) of them. PATIENTS, METHODS: NIS expression of 27 primary tumours, 13 lymphnodes and 18 distant metastases was determined by immunostaining using a murine monoclonal anti-NIS-antibody. NIS expression and radionuclide uptake of metastases were analysed by a semiquantitative visual score. Patients were divided into two subgroups: Group 1 (n = 8 patients): indirect correlation of radioiodine uptake (RIU) of subsequent metastases with NIS expression of 7 primary tumours and 3 metastases; Group 2 (n=11 patients): direct correlation of radionuclide uptake with NIS expression of 19 metastases which were excised after imaging. RESULTS: 49 of 58 specimens (84.5%) were NIS-positive. A preserved NIS-expression was found in 12 primary tumours and 8 of 10 (80%) synchrone and 6 of 7 (85.7%) metachrone metastases. Group 1 revealed a 100% positive predictive value (PPV) of a preserved NIS expression in the primary tumour regarding radioiodine uptake in metastases while a lack of NIS expression in the primary tumor did not reliable predict a loss of the metastases' ability to concentrate radioiodine. In group 2, only 11 of 19 (57.9%) specimens showed a concordant NIS expression and RIU whereas in the remaining 8 cases without visible RIU NIS expression was still present. CONCLUSIONS: NIS expression of the primary tumour and metastases in DTC is usually well preserved. We found a positive correlation between NIS expression of the primary and metastatic tissue but could not identify such well correspondence between NIS expression and the RIU of subsequent metastases.

Potential of OUR and OTR measurements for identification of activated sludge removal processes in aerated basins.

In order to develop a process control scheme to reduce energy costs for aeration in activated sludge systems with biological P removal, pre-denitrification and nitrification stages, the spatial distribution of carbon oxidation and nitrification was evaluated over a long full-scale plug flow aeration basin using an externally measured specific oxygen uptake rate (sOUR) and in basin measurement of the actual specific oxygen transfer rate (sOTR) with off-gas testing as well as with the calculated oxygen demand from NH4-N concentrations (sOTR(N)). Using a simple static model, a gas phase balance on oxygen and carbon dioxide, sOTR(N) values were also calculated from off-gas testing. Comparison of sOTR(N) to sOTR and sOUR for carbon oxidation (sOUR(C)) to nitrification (sOUR(N)) at different loading conditions allowed the oxidation processes to be followed over the three zones of the aeration basin. As expected, the distribution depended on the dissolved oxygen concentration (DO) in the basin. However, the major change was in the C-oxidation rate and not the nitrification rate. At a low DO, and when NH4-N was present in the zone, the amount of oxygen transferred for nitrification was nearly the same, but the overall sOTR was lower. The externally measured sOUR was only useful when it was differentiated into sOUR(N) and sOUR(C). sOUR(N) could be used to predict the nitrification rate in the basin. With further refinement, the gas phase balance model has potential to be used to monitor the degree of nitrification over the basin length. This can be integrated into a control scheme to reduce aeration costs by adjusting the DO setpoint according to loading conditions in the

A control strategy for reducing aeration costs during low loading periods.

The efficiency of the aeration system in a full-scale activated sludge basin with 3 separately controlled aeration zones was improved for the low loading period in summer. The air flow rate to each aeration zone is currently regulated to hold a preset dissolved oxygen concentration (DO). Four different DO setpoint combinations were tested, each one for a one week period, using dynamic off-gas testing to measure the standardised oxygen transfer efficiency (alphaSOTE). As the DO setpoints were lowered, the total air flow rate to the basin decreased initially. A low DO in the first zones slowed biomass activity and pushed the load towards the end of the aeration basin. The relationship between alphaSOTE and the specific diffuser flow rate qD is different for each zone. In Zone 1 there was a strong decrease in alphaSOTE as qD increased, while Zones 2 and 3 were fairly independent of qD, Zone 2 at a higher level than Zone 3. Aeration costs were reduced by 15% for the most efficient combination. To achieve even more savings, a control strategy adjusting oxygen transfer rates over the aeration basin to the necessary oxygen transfer rates is suggested. It is based on changing the DO setpoints to reach the lowest total air flow rate while meeting the effluent requirements.