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A novel approach of using two stage anaerobic digestion coupled with electrodialysis technology has been investigated. This approach was used to improving bio hydrogen and methane yields from food waste while simultaneously producing a green chemical feedstock. The first digester was used for hydrogen production and the second digester was used for methane production. The first digester was combined with continuous separation of volatile fatty acids using electrodialysis. The concentrations of carbohydrates, proteins and fats in the prepared food waste were 22.7%, 5.7% and 5.2% respectively. Continuous removal of volatile fatty acids during fermentation in the hydrogen digester not only increased hydrogen yields but also increased the production rate of volatile fatty acids. As a result of continuous VFA separation, hydrogen yields increased from 17.3 mL H2/g VS fermenter to 33.68 mL H2/g VS fermenter. Methane yields also increased from 28.94 mL CH4/g VS fermenter to 43.94 mL CH4/g VS fermenter. This represents a total increase in bio-energy yields of 77.1%. COD reduced by 73% after using two stage anaerobic digestion, however, this reduction increased to 86.7% after using electrodialysis technology for separation of volatile fatty acids. Electrodialysis technology coupled with anaerobic digestion improved substrate utilization, increased bioenergy yields and looks to be promising for treating complex wastes such as food waste.

A novel method to recover VFAs from a continually-fed 100 L food waste bioreactor was developed using industrially applicable methods. The in-situ recovery of VFAs increased production rates from 4 to 35 mgvfa gvs−1 day−1 by alleviating end-product inhibition and arresting methanogenesis, and electrodialysis was able to concentrate the recovered VFAs to 4000 mg L−1. There remains considerable scope to increase the production rates and concentrations further, and the VFAs were recovered in a form that made them suitable for use as platform chemicals with minimal refining. This is the first time that continuous VFA recovery from real-world food waste has been reported at this scale with continual feeding, and represents a promising means through which to produce sustainable platform chemicals. Furthermore the production of VFAs arrests methane production in bioreactors, which is a low value product around which there is a growing concern about fugitive emissions contributing to climate change.

There is growing national and international concern about the mental health of children and young people, and in countries such as England there is now a political and policy commitment to developing whole-school approaches to mental health. This paper presents new evidence on how pupils’ mental health is being addressed in schools using learning activities associated with physical education, sport and physical activity, as part of a school-based sport- and mental health-themed programme (‘Tackling the Blues’) for pupils aged 6–16 years old in north-west England. In particular, we examine how pupil-centred learning activities have been used in weekly multi-sport activity sessions and related classroom-based workshops, and draw upon insight from 29 focus groups to explore pupils’ ( n = 116) mental health awareness and associated socio-emotional learning (SEL). The learning activities led pupils to focus on the impact personal relationships with family and friends, feelings and emotions, and experiences of stress, anger and entrapment can have on mental health. It is argued that embedding socially relevant learning activities into the content, organisation and delivery of school curricula may help improve pupils’ sense of enjoyment, participation and achievement which are important for enhancing their knowledge and awareness of mental health, and developing SEL. However, we conclude that the effectiveness of whole-school approaches also depends, perhaps to a greater degree, on the wider educational systems in which schools are located and especially the widening social, economic and health inequalities which have profound impacts on child development, educational and other outcomes, and mental health.

OBJECTIVES: Although testicular cancer (TC) is the most common tumor in young men in Western countries, there is no official cancer detection/screening program for young men in Germany. The most important TC detection tool is self-examination of the testis. Hypothetically medical students may have a diagnosis lead time and detection superiority. This study was designed to analyze whether medical students have a possible knowledge advantage over students of other faculties concerning TC and to compare male and female cancer screening demeanor and mentality. METHODS: Male and female students of various faculties at the Goethe University Frankfurt/Main, Germany were invited to participate in this internet-based anonymous questionnaire with questions about TC awareness/knowledge, testicular (self) examination, and cancer screening behavior. RESULTS: In total 1,049 students (329 medical and 716 non-medical students) completed the questionnaire. In general, medical students had a significantly higher TC knowledge, especially in the more advanced stages of their medical studies (year 3-6). About 50% of medical students had knowledge of TC whereas only 21.3% of non-medical students knew about the disease (p < 0.01). In addition, medical students conducted scrotal examinations more frequently (34.7%) than non-medical students (18.8%). CONCLUSION: The knowledge about TC is low among students. In general, medical students are more aware of TC and perform more frequent testicular examinations compared to non-medical students. Female TC knowledge rises in the clinical part of studies to the same level as their male counterparts, with the result of more testicular partner examinations.

Work considering the influence of power dynamics and potential confounders such as social status is beginning to receive more attention in physical education literature. While power dynamics deserve particular attention in student-centred and social constructivist pedagogies, exploration of this topic has largely escaped the grasp of Game-Based Approaches (GBAs). This position paper aimed to review current micro-interactional research in physical education and to propose the utilisation of four key principles as a means to disrupt power dynamics in GBAs, namely: (a) teaching paradoxically; (b) ethical dilemmas; (c) unfamiliar games; and (d) Socratic questioning. Two illustrative vignettes present the practical application of these principles to produce a state referred to in Classical Greece as Aporia (impasse or without passage). Building on the work of Joy Butler, we argue that student insights gained in these moments of Aporia are central to the disruption of power-based barriers to learning.

Although biofilters and bioretention controls have been extensively studied and are encouraged as effective stormwater controls, there is remaining uncertainty concerning their long-term pe...

Stormwater biofilters and bioretention controls have been extensively studied and are commonly encouraged as effective stormwater controls. Most of these controls incorporate media to enhan...

A novel combination of solids screening, centrifugation, microfiltration, pervaporation, and electrodialysis were used for the targeted and exclusive recovery of volatile fatty acids (VFAs) from an 80 L bioreactor. The bioreactor was continually–fed with grass waste, containing 40 g L–1 total solids, over three, seven–day, hydraulic retention times. A VFA solution with a concentration up to 4,500 mg L–1 was recovered. VFA yields were also increased from 707 to 875 mg of VFA per gram of volatile solids by alleviating end–product inhibition. Both these accomplishments are significant step–changes in adding value to waste, and increased substrate utilisation rates will be attractive from a waste remediation perspective.

A novel approach of using two stage anaerobic digestion coupled with electrodialysis technology has been investigated. This approach was used to improving bio hydrogen and methane yields from food waste while simultaneously producing a green chemical feedstock. The first digester was used for hydrogen production and the second digester was used for methane production. The first digester was combined with continuous separation of volatile fatty acids using electrodialysis. The concentrations of carbohydrates, proteins and fats in the prepared food waste were 22.7%, 5.7% and 5.2% respectively. Continuous removal of volatile fatty acids during fermentation in the hydrogen digester not only increased hydrogen yields but also increased the production rate of volatile fatty acids. As a result of continuous VFA separation, hydrogen yields increased from 17.3 mL H

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and have become more difficult to treat over the years. Inappropriate antibiotic use has led to increased antibiotic resistance.We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility. We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years.In our hospital-based analysis, cystitis was the most frequently diagnosed UTI in women (76%) and men (79%).Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs. When selecting an optimal antimicrobial treatment regimen for patients with UTIs, it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns. Therefore, continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized.

The meat and dairy industry across Europe is dependent on the production of grass. However, faced with competing pressures to reduce the environmental impact of agriculture, a potential future reduction of meat and dairy consumption in western diets, and pressure to minimize food production costs, grass could be used to produce alternative products. The biological production of polyhydroxyalkanoates (PHA) by using grass as the primary carbon source in a novel mixed culture process has been studied. A total of 30,000 t of fresh grass would yield approximately 403.65 t of dried biopolymer granules. On the basis of this early stage, non‐optimized process, the cumulative energy demand (CED) of PHA produced from waste grass and cultivated grass was found to be 248.4 MJ/kg and 271.8 MJ/kg, respectively, which is the same order of magnitude as fossil‐carbon‐based polymers. Improvements in volatile fatty acid yields, reduction in chemical and water inputs, and using residues to make other products will reduce the CED. Given the future requirement to produce polymers with little or no fossil‐carbon feedstock, an optimized version of the process could provide a viable future production option that also contributes to the long‐term sustainability of agricultural communities.

Introduction: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). Methods: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. Results: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4–7) for TUR-P, 9 days (IQR: 7–11) for OP, and 5 days (IQR: 4–6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27–8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12–22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03–3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74–3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56–7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66–2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. Conclusion: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.

There is growing international concern about the mental health of those who work in sport, including coaches. However, we currently know little about the prevalence of mental illness and the experience of mental health among coaches, and their perceptions and use of workplace mental health support services. Little is also known about coaches&rsquo, disclosure of mental illness to, and seeking help from, work colleagues. We explore these issues using data from 202 coaches who responded to the first United Kingdom survey of mental health in the sport and physical activity workforce. In total, 55% of coaches reported having ever experienced a mental illness, and 44% currently did, with coaches in grassroots/community settings being most likely to experience mental illness. Depression and anxiety were the most commonly reported conditions and many coaches preferred to access mental health support outside of the organisation for whom they worked or volunteered, with decisions to seek help from others in the workplace being shaped by complex organisational and personal considerations. The findings suggest there is an important public health challenge which needs to be met among coaches, so that we can better address a question of fundamental importance: &lsquo, who is looking after the people looking after the people&rsquo

Die fokale Therapie ist bei kleinen Nierentumoren eine Alternative zur chirurgischen Entfernung. Jedoch sind bei einzelnen Verfahren hohe Lokalrezidivraten und klinisch ernstzunehmende Komplikationen beobachtet worden. Eine pratherapeutische Nierenbiopsie sowie eine strenge Indikationsstellung konnen daher erforderlich sein.

Petrochemically-derived platform chemical dependence is incompatible with decarbonisation targets, and the production rate of waste is increasing. Carboxylic acids are produced by fermenting organic waste; a process that also remediates the waste's environmental impacts. Biogas is the dominant product of industrial-scale waste fermentations however carboxylates are more economically valuable than biogas and are more sustainable. This has propagated interest in producing and recovering carboxylates over biogas. This review catalogues and normalises recent carboxylate production and recovery data, making the studies more readily comparable whilst identifying the gaps in the literature. It was found there is little consensus around the optimum production and recovery methodologies for carboxylates, with limited consideration of the economic and environmental implications of these processes. More work is needed, at pilot scale and larger, focussing on the carboxylate production and recovery methodologies most applicable to industry, and to establish a consensus around the optimisation of these processes.

The purpose of this study was to identify specific factors affecting the retention of secondary agriculture teachers. The six factors data were collected on included educational preparation, teacher commitment, first year teaching experience, skills and abilities, social integration, and institutional factors. Participants in this study perceived factors contributing to educational preparation as 'good' with no exceptional ratings. Respondents 'agreed' with the nine items pertaining to teacher commitment and all 21 items within the skills and abilities category. Gaining student respect was rated as an extremely important part of social integration in their teaching career. Although participants agreed with five of the six items in the first year teaching experience, they were undecided in their confidence in curriculum development. Twenty-six of the 30 items within the institutional factors were rated as very important with administrative support for program development ranking the highest.

An industrially applicable methodology utilising a novel combination of filtration and electrochemical separation technologies was successfully used to recover, and enhance the production of, volatile fatty acids from an 82.5 L bioreactor, continually fed with grass at 5% total solids. Volatile fatty acid yields were increased from 287 to 404 mgvfa gvs−1 and concentrated up to 4800 mg L−1 in a solution suitable for downstream conversion to platform chemicals. This work also shows that there is considerable headroom to increase further volatile fatty acid recovery rates and yields by increasing the capacity of the recovery methodology. The novel methodology developed herein could help to address some of the environmental and economic concerns that have led to the need to diversify the ways in which grass is used as a resource, and represents an alternative to petrochemicals as a carbon source for platform chemical production.

This chapter discusses the initial design and development of an on-going sport and education-based mental health programme – Tackling the Blues (TtB) – which was introduced in January 2015 for primary and secondary school-aged children and young people (CYP) who are experiencing, or are at risk of developing mental illness. It examines how participants were identified, recruited and engaged, and the features of the selected theoretical framework, that is realist evaluation, which underpinned the programme. The chapter explores the lessons learned from using the brand of a professional football club to engage CYP and the training and use of university student peer mentors. It describes the inevitable limitations of the programme imposed by the various inequalities which beset the participants’ lives. TtB is an on-going programme which at the time of writing was nearing the end of its second year of delivery.

The impact of continuous removal of volatile fatty acids on fermentative hydrogen productionfrom food waste (FW) in a Continuously Stirred Tank Reactor (CSTR) was evaluated. Two experimental phases were conducted, a control phase and one in which volatilefatty acids were removed continuously from the reactor for the first time by electrodialysis(ED). Hydrogen yields were 64.7 cm3 H2/g VS and 227.3 cm3 H2/g VS for control phase, and ED phase respectively. Continuous removal of volatile fatty acids during fermentation notonly increased H2 yields but increased the production of volatile fatty acids (a valuablechemical feedstock) from 0.14 g/g VS to 0.34 g/g VS.

Chimeric antigen receptor (CAR) T cell therapy for hematologic malignancies is fraught with several unknowns, including number of functional T cells that engage target tumor, durability and subsequent expansion and contraction of that engagement, and whether toxicity can be managed. Non-invasive, serial imaging of CAR T cell therapy using a reporter transgene can address those issues quantitatively. We have transduced anti-CD19 CAR T cells with the prostate-specific membrane antigen (PSMA) because it is a human protein with restricted normal tissue expression and has an expanding array of positron emission tomography (PET) and therapeutic radioligands. We demonstrate that CD19-tPSMA(N9del) CAR T cells can be tracked with [18F]DCFPyL PET in a Nalm6 model of acute lymphoblastic leukemia. Divergence between the number of CD19-tPSMA(N9del) CAR T cells in peripheral blood and bone marrow and those in tumor was evident. These findings underscore the need for non-invasive repeatable monitoring of CAR T cell disposition clinically.

To compare the effect of different diameters of ureteral stents (F4.7, F6, and F7) on quality of life regarding the subdomains of the Ureteral Stent Symptom Questionnaire.All patients undergoing URS between April 2016 and July 2017 were prospectively randomised for ureteral stents F4.7, F6 and F7, respectively. All patients with other pathologies than a ureter stone, ureteral stents on both sides or other therapy than a secondary URS were excluded. Readmitted patients were interviewed using the USSQ. Furthermore, success rates of the second URS were also noted.Between April 2016 to July 2017, 181 patients were included, 48 with a ureteral stent F4.6, 66 with F6 and 67 with F7. No significant differences in age, gender or position of the stones before URS were found (all p 0.5). Comparing scores of USSQ between F4.7 and F6 or F6 and F7, scores were in favour of the smaller stent, but significance was only reached in "Work performance score" (F6-F7, p = 0.04) and "Urinary index score" (F4.7-F6, p = 0.004). When comparing F4.7 with F7, significant differences in all subgroups in favour of F4.7 were documented (all p 0.03). Surgical success of the second URS was comparable in all groups (all above 82%, p 0.15).Discomfort and pain increase with the diameter of the indwelling ureter stent, while the success of the following URS is not compromised by a ureter stent with a smaller diameter. Therefore, ureteral stents with a small diameter should be preferred.

The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on malignant plasma cells. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin–biotin pretargeted RIT (PRIT) directed against the CD38 antigen were assessed as approaches to deliver radiation doses sufficient for multiple myeloma cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24 hours after PRIT, whereas ratios never exceeded 1:1 with conventional RIT. 90Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 to 1,200 μCi of anti-CD38 pretargeted 90Y–DOTA–biotin, including 100% complete remissions (no detectable tumor in treated mice compared with tumors that were 2,982% ± 2,834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 μCi of anti-CD38 pretargeted 90Y–DOTA–biotin achieved long-term myeloma-free survival (>70 days) compared with none (0%) of the control animals. Cancer Res; 74(4); 1179–89. ©2013 AACR.

Electrodialysis (ED) removed volatile fatty acids (VFAs) from a continually-fed, hydrogen-producing fermenter. Simultaneously, electrochemical removal and adsorption removed gaseous H2 and CO2, respectively. Removing VFAs via ED in this novel process increased H2 yields by a factor of 3.75 from 0.24 mol H2 mol−1hexose to 0.90 mol H2 mol−1hexose. VFA production and substrate utilisation rates were consistent with the hypothesis that end product inhibition arrests H2 production. The methodology facilitated the recovery of 37 g of VFAs, and 30 L H2 that was more than 99% pure, both of which are valuable, energy dense chemicals. Typically, short hydraulic and solid retention times, and depressed pH levels are used to suppress methanogenesis, but this limits H2 production. To produce H2 from real world, low grade biomass containing complex carbohydrates, longer hydraulic retention times (HRTs) are required. The proposed system increased H2 yields via increased substrate utilisation over longer HRTs.

The use of electrochemical hydrogen removal (EHR) together with carbon dioxide removal (CDR) was demonstrated for the first time using a continuous hydrogen producing fermenter. CDR alone was found to increase hydrogen yields from 0.07molH2molhexose to 0.72molH2molhexose. When CDR was combined with EHR, hydrogen yields increased further to 1.79molH2molhexose. The pattern of carbohydrate utilisation and volatile fatty acid (VFA) production are consistent with the hypothesis that increased yields are the result of relieving end product inhibition and inhibition of microbial hydrogen consumption. In situ removal of hydrogen and carbon dioxide as demonstrated here not only increase hydrogen yield but also produces a relatively pure product gas and unlike other approaches can be used to enhance conventional, mesophilic, CSTR type fermentation of low grade/high solids biomass.

To preserve renal function, nephron sparing surgery (NSS) for renal tumors should be performed. Little is known about perioperative morbidity and long-term functional outcome of patients after elective NSS compared with radical nephrectomy (RN) in renal tumors4 cm.Eight-hundred twenty-nine patients were treated with either RN (n = 641) or NSS (n = 188) for renal tumors4 cm. After pairing the cohort for age, grading, TNM, size, gender, and preoperative renal function and excluding patients with imperative indication and metastases, 247 patients remained for functional analysis. Serum creatinine (SCr) values were used to estimate glomerular filtration rate (eGFR) via Modification of Diet in Renal Disease. Chronic kidney disease (CKD) was defined as eGFR60 mL/min/1.73 m(2) and regression analyses were used to identify clinical risk factors for CKD and perioperative complications stratified by the Clavien-Dindo score.The Charlson comorbidity index was similar between patients undergoing NSS (n = 101) and RN (n = 146) (P = .583). The complication rates did not differ significantly between both groups (P = .091). Age (OR 0.94, P = .009), ASA score 3+4 (OR 3.55, P = .004), RN (OR 10.75, P.001), and preoperative eGFR (OR 1.06, P.001) were independent risk factors for developing CKD postoperatively, whereas tumor size had no impact (OR 1.01, P = .245). Overall survival was comparable between the groups (P = .896).Although overall survival was similar, patients undergoing RN for renal tumors4 cm had a significantly higher risk of developing CKD than patients treated with NSS. Complication rate did not differ significantly between both groups, even for tumors7 cm. Our findings support elective NSS for tumors4 cm, whenever NSS is technically feasible for maintaining renal function.

Introduction In this study, we aimed to determine those clinical and pathologic features that are associated with pelvic lymph node metastasis in patients with transitional cell cancer of the bladder. Unlike previous studies, we particularly focused on intravesical tumor location. Methods We included 173 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for muscle-invasive or high-risk superficial bladder cancer. Fifty patients (28.9%) presented with lymph node metastases. Tumor-related and personal characteristics were analyzed. Results Lymph node positive disease occurred in association with an increasing pathologic tumor stage ( P − 6 ) and with a decreasing differentiation status ( P = 0.008). The rate of pelvic lymph node metastasis differed in primary tumors growing on different intravesical locations. Cancers located exclusively on the lateral bladder walls ( P − 5 ) and tumors involving the lateral walls ( P = 0.042) were highly correlated with lymph node positive disease. Posterior wall tumors were least associated with lymph node metastases compared with other tumor locations ( P = 0.015). Focal tumor growths located on the lateral bladder wall and an increasing pathologic tumor stage and decreasing differentiation-status were identified as independent risk factors for the pelvic lymph node status. Conclusions For the first time we present the association of intravesical tumor location and the rate of lymph node metastasis in transitional cell cancer of the bladder. Our findings may ultimately contribute to a more individualized patient management.

The high design standards for the preservation of the urban water environment result in more detention basins in residential areas. The steep channel and outfall pipe from a detention basin can be hazardous to children and small animals. During an event, a trapped person may flow with water toward the outfall entrance. When the outfall pipe is gradually blocked, the flow force acting on the blocking body can be pinning at the beginning to eventually deadly. It is not clear as to how to quantify the pinning force on the block during the closure of flow because the number of unknown forces is greater than the number of equations for force balance. This paper presents a new approach using the method of superposition to calculate the pinning force with and without a blockage at the culvert entrance. The analysis conducted in this paper verifies that the pinning force on the clogging block is dominated by the flow dynamic force until the flow becomes discontinued. As soon as the hydrostatic force is developed, the pinning force can be lethal. This study confirms that an outfall pipe shall be protected by a trash rack with its surface area 4 times the culvert opening area. As long as the continuity of flow is sustained by the blocked rack, the hydrostatic force will not be developed or a chance for survival remains.

Konventionelle Masnahmen zur Therapie des fortgeschrittenen Nierenzellkarzinoms (NZK) sind limitiert. Rezeptortyrosinkinaseinhibitoren (RTKI) eroffnen neue Behandlungsoptionen. Wir evaluierten die Wirkung des RTKI AEE788 auf das Wachstum und die Adhasionskapazitat von NZK-Zelllinien in vitro. NZK-Zellen wurden mit AEE788 behandelt und die daraus resultierenden Veranderungen im Wachstumsverhalten sowie die Interaktion mit dem Gefasendothel und Extrazellularmatrixproteinen ermittelt. Es wurde zusatzlich gepruft, ob die gleichzeitige Applikation von Interferon-α (IFN-α) die Effizienz von AEE788 steigern kann. AEE788 fuhrte zu einer signifikanten Hemmung des Tumorzellwachstums und der Adhasion. Rezeptoranalysen ergaben eine Modulation von Integrinproteinen des α- und β-Subtyps sowie eine Hemmung der integrinabhangigen Signalkaskade. Die kombinierte Anwendung von IFN-α und AEE788 bewirkte eine starkere Blockade des Tumorwachstums und der intrazellularen Signalaktivitat, als die alleinige Gabe von AEE788. AEE788 zeigt signifikante antitumorale Eigenschaften, insbesondere in Kombination mit IFN-α, und prasentiert somit eine vielversprechende Substanz zur Behandlung des fortgeschrittenen NZK.

Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-alpha (IFN-alpha) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA-IFN-alpha combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC.

The purpose of this retrospective study was to evaluate the results of the Eurotransplant Senior Programme (ESP) within our centre compared to elderly recipientsor=60 years from the regular Eurotransplant Kidney Allocation System (ETKAS), specifically focusing on surgical aspects.Data from 73 ESP patients (average donor/recipient age: 71.1/67.1) were compared with those from 51 patients (49.7/63.6) treated within the framework of the ETKAS program between the years 1999 and 2006. The mean follow-up was 39.5 months.Cold ischaemic time (ESP versus ETKAS: 10.3 versus 15.0 h), duration of renal replacement therapy (42.2 versus 76.8 months), donor glomerular filtration rate (81.7 versus 109.9 ml/min/1.73 m(2)) and HLA mismatches (4.1 versus 2.4) were significantly different between the two groups (all P0.001). Primary graft function was seen in 74% ESP versus 69% of ETKAS patients (P0.05). The rate of surgical complications in the ESP versus ETKAS group was 47% versus 28% (P = 0.031) and the revision rate, 33% versus 24% (P = 0.259). Three-year patient and censored graft survival was 84% versus 92% and 85% versus 88% in the ESP and ETKAS group, respectively (all P0.05). Ninety-five percent of all deceased patients died with a functioning graft.The donor and recipient pool has been markedly expanded through ESP with similar patient and graft survival compared to elderly recipients grafted according to ETKAS criteria. However, patients and their physicians should be aware of the high surgical complication rate in elderly recipients, particularly when receiving elderly donor kidneys. This might seriously influence postoperative patient management but ultimately does not compromise the transplant outcome.