Role of the Iodide-Methylammonium Interaction in the Ferroelectricity of CH3 NH3 PbI3.

Excellent conversion efficiencies of over 20 % and facile cell production have placed hybrid perovskites at the forefront of novel solar cell materials, with CH3 NH3 PbI3 being an archetypal compound. The question why CH3 NH3 PbI3 has such extraordinary characteristics, particularly a very efficient power conversion from absorbed light to electrical power, is hotly debated, with ferroelectricity being a promising candidate. This does, however, require the crystal structure to be non-centrosymmetric and we herein present crystallographic evidence as to how the symmetry breaking occurs on a crystallographic and, therefore, long-range level. Although the molecular cation CH3 NH3 + is intrinsically polar, it is heavily disordered and this cannot be the sole reason for the ferroelectricity. We show that it, nonetheless, plays an important role, as it distorts the neighboring iodide positions from their centrosymmetric positions.

Why does a point of care guided transfusion algorithm not improve blood loss and transfusion practice in patients undergoing high-risk cardiac surgery? A prospective randomized controlled pilot study.

BACKGROUND: Adult cardiac surgery is often complicated by elevated blood losses that account for elevated transfusion requirements. Perioperative bleeding and transfusion of blood products are major risk factors for morbidity and mortality. Timely diagnostic and goal-directed therapies aim at the reduction of bleeding and need for allogeneic transfusions. METHODS: Single-centre, prospective, randomized trial assessing blood loss and transfusion requirements of 26 adult patients undergoing elective cardiac surgery at high risk for perioperative bleeding. Primary endpoint was blood loss at 24 h postoperatively. Random assignment to intra- and postoperative haemostatic management following either an algorithm based on conventional coagulation assays (conventional group: platelet count, aPTT, PT, fibrinogen) or based on point-of-care (PoC-group) monitoring, i.e. activated rotational thromboelastometry (ROTEM®) combined with multiple aggregometry (Multiplate®). Differences between groups were analysed using nonparametric tests for independent samples. RESULTS: The study was terminated after interim analysis (n = 26). Chest tube drainage volume was 360 ml (IQR 229-599 ml) in the conventional group, and 380 ml (IQR 310-590 ml) in the PoC-group (p = 0.767) after 24 h. Basic patient characteristics, results of PoC coagulation assays, and transfusion requirements of red blood cells and fresh frozen plasma did not differ between groups. Coagulation results were comparable. Platelets were transfused in the PoC group only. CONCLUSION: Blood loss via chest tube drainage and transfusion amounts were not different comparing PoC- and central lab-driven transfusion algorithms in subjects that underwent high-risk cardiac surgery. Routine PoC coagulation diagnostics do not seem to be beneficial when actual blood loss is low. High risk procedures might not suffice as a sole risk factor for increased blood loss. TRIAL REGISTRATION: NCT01402739 , Date of registration July 26, 2011.

Molecular detection of Salmonella serovars Enteritidis, Heidelberg and Typhimurium directly from pre-enriched poultry samples.

1. Salmonella is one of the most important pathogens in public health and it is usually associated with food-borne diseases. Salmonella serovars Enteritidis and Typhimurium are widespread in the world with outbreaks frequently associated with consumption of poultry products; furthermore, there is an increasing public health concern with the wide dissemination of the serovar Heidelberg in poultry flocks. 2. The aim of the experiment was to develop and to validate rapid methods to detect Salmonella serovars Enteritidis, Typhimurium, and Heidelberg by real-time PCRs and test isolates from pre-enriched poultry samples. 3. Three real-time PCRs were developed and used in combination to detect the serovars Enteritidis, Typhimurium and Heidelberg. These assays were validated by the analysis of 126 Salmonella isolates, eight other enteric bacterial species and 34 naturally contaminated poultry samples after pre-enrichment with buffered peptone water (BPW). 4. Real-time PCRs detected the isolates of the most important poultry serovars (Enteritidis, Typhimurium and Heidelberg) with 100% inclusivity and exclusivity in each assay. The PCR identified monophasic variants of the serovars Typhimurium and Heidelberg. All PCRs were validated in detecting these specific serovars directly from pre-enriched poultry samples. The whole analytical procedure was performed in less than 24 h in a veterinary diagnostic laboratory.

Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study.

PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination. RESULTS: Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely. CONCLUSIONS: Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.

[Cardiovascular disease in pediatric patients under chronic peritoneal dialysis]. / Compromiso cardiovascular en pacientes pediátricos en diálisis peritoneal crónica.

Peritoneal dialysis (PD) is the most common renal replacement therapy used in pediatric patients with end stage renal disease. This population has a mortality rate 1,000 times greater compare to pediatric population, mainly due to cardiovascular causes. OBJECTIVE: To characterize pediatric patients on chronic PD in relation to dialysis and cardiovascular outcome. PATIENTS AND METHODS: Cross sectional study. Patients in stable PD according to DOQI criteria were selected. Epidemiological, dialytic, biochemical and cardiovascular variables were registered. Left Ventricular Mass Index (LVMI) was calculated by height/age (g/m2.7). Left Ventricular Hypertrophy (LVH) was diagnosed with > 38.6 g/m2.7, severe LVH > 51 g/m2.7. Data were analyzed using STATA 11.0. continuous variables using ANOVA test and categorical variables were analyzed using χ2 test or Fisher’s exact test. RESULTS: 21 patients, 11 males. Mean age 9.2 ± 3.52 years. The most frequent diagnosis was renal dysplasia (52%). Residual and Peritoneal KtV were 0.8 and 1.9 respectively. Fifty-two percent of patients showed LVH, 91% in severe range. A significant relationship between ultrafiltration/m2 and systolic blood pressure was depicted. Also a significant relationship between left ventricular mass index and hemoglobin (p < 0.05) was founded. CONCLUSIONS: The majority of the population showed left ventricular hypertrophy -particularly severe LVH-, which confirms an increased CV risk in this population. Blood pressure and loss of ultrafiltration were founded to be correlated to LVH.

Bumblebee Flight in Heavy Turbulence.

High-resolution numerical simulations of a tethered model bumblebee in forward flight are performed superimposing homogeneous isotropic turbulent fluctuations to the uniform inflow. Despite tremendous variation in turbulence intensity, between 17% and 99% with respect to the mean flow, we do not find significant changes in cycle-averaged aerodynamic forces, moments, or flight power when averaged over realizations, compared to laminar inflow conditions. The variance of aerodynamic measures, however, significantly increases with increasing turbulence intensity, which may explain flight instabilities observed in freely flying bees.

Detection of genetically modified maize in processed products, dry grains, and corn ears intended for fresh consumption in South Brazil.

Conventional and genetically modified (GM) maize cultivars have been widely planted in Brazil to produce grains for processed food, feed, or to be consumed fresh as corn ears. This study used real-time PCR to detect GM maize in processed products and fresh commercial corn ears produced in the last two years in South Brazil. Eighteen conventional and GM maize cultivars were obtained from seed production companies and 50 commercial samples (including canned corn, corn flour, dry grains, and fresh corn ears) were purchased in small local stores and supermarkets. All samples were analyzed by real time TaqMan PCR to detect one constitutive maize gene (hmg) and three genetic regions present in GM plants (p-35S promoter, major gene cry 1A.105, and t-Nos terminator). Each commercial sample was classified as conventional or GM based on the PCR results. PCR targeting the hmg gene generated positive results from all DNA samples, which were further tested with the GM targets. These targets were not detected in the five conventional maize cultivars, but were detected in the GM seeds hosting these fragments. Analysis of processed foods identified four cultivars as conventional and six as GM, which were mostly correctly labeled. Seven (53.8%) dry grain samples were classified as conventional, while six (46.2%) were classified as GM. Three (11.1%) corn ear samples were identified as conventional, and the remaining 24 (88.9%) were GM maize. These results demonstrate the high frequency of GM maize in processed products, including fresh corn ears intended for consumption in South Brazil.

[Changing structures--Integrating health]. / Strukturen ändern--Gesundheit integrieren.

Changes in (municipal) structures for the improvement of health are often required but, in contrast to behavioural measures, less frequently implemented and scientifically evaluated. Results on this subject for Germany are scarce. In recent years, municipal prevention and health promotion programmes received new impetus from the expansion of the German "Early Assistance" initiative. Early assistance programmes to help children grow up healthy initiated municipal processes such as the establishment of networks between health services and youth welfare services, prevention chains and nationwide initiatives. This has moved issues such as equal opportunities for health into the centre of politically driven structural development efforts. Neighbourhood management groups and municipal round tables on prevention-specific topics etc. have been established throughout Germany. Regarding this structural development, 6 projects from the field of prevention research give a good indication as to how the structure of municipal concepts can be effectively implemented.

[Reaching Target Groups--Shaping Accessibility. Results of a Survey Among Experts on Recommendations for Science and Practice]. / Zielgruppen erreichen--Zugangswege gestalten. Ergebnisse einer Befragung von Expertinnen und Experten zu Empfehlungen für Wissenschaft und Praxis.

In an online survey, in which 18 experts participated, recommendations for research and practice to improve access to target groups were discussed. The recommendations were developed within the context of the KNP project. For the implementation of the recommendations, not only is an increased cooperation between science and practice particularly important, but also materials and training as well as standardization of methods. Furthermore, financial resources, especially for conducting evaluation studies are needed.

Matching spiracle opening to metabolic need during flight in Drosophila.

The respiratory exchange system of insects must maximize the flux of respiratory gases through the spiracles of the tracheal system while minimizing water loss. This trade-off between gas exchange and water loss becomes crucial when locomotor activity is increased during flight and metabolic needs are greatest. Insects that keep their spiracles mostly closed during flight reduce water loss but limit the flux of oxygen and carbon dioxide into and out of the tracheal system and thus attenuate locomotor performance. Insects that keep their spiracles completely open allow maximum gas exchange but face desiccation stress more quickly. Experiments in which water vapor was used as a tracer gas to track changes in the conductance of the respiratory system indicated that flying fruit flies minimize potential water loss by matching the area of the open spiracles to their gas exchange required for metabolic needs. This behavior maintained approximately constant pressure for carbon dioxide (1.35 kilopascals) and oxygen (19.9 kilopascals) within the tracheal system while reducing respirometric water loss by up to 23% compared with a strategy in which the spiracles are held wide open during flight. The adaptive spiracle-closing behavior in fruit flies has general implications for the ecology of flying insects because it shows how these animals may cope with environmental challenges during high locomotor performance.

Wing rotation and the aerodynamic basis of insect flight.

The enhanced aerodynamic performance of insects results from an interaction of three distinct yet interactive mechanisms: delayed stall, rotational circulation, and wake capture. Delayed stall functions during the translational portions of the stroke, when the wings sweep through the air with a large angle of attack. In contrast, rotational circulation and wake capture generate aerodynamic forces during stroke reversals, when the wings rapidly rotate and change direction. In addition to contributing to the lift required to keep an insect aloft, these two rotational mechanisms provide a potent means by which the animal can modulate the direction and magnitude of flight forces during steering maneuvers. A comprehensive theory incorporating both translational and rotational mechanisms may explain the diverse patterns of wing motion displayed by different species of insects.

[Preoperative therapy switch before glaucoma filtration surgery : Influence of the systemic antiglaucomatous and local antiphlogistic therapy on the intraocular pressure]. / Präoperative Therapieumstellung vor filtrierender Glaukomchirurgie : Einfluss der systemischen augendrucksenkenden sowie der lokalen antiphlogistischen Therapie auf den Augendruck.

BACKGROUND: The preoperative switch from local to systemic antiglaucomatous therapy and the additional application of local antiphlogistic drugs represents an important component of perioperative wound healing modulation within the framework of glaucoma filtration surgery. OBJECTIVE: The aim of the present study was to compare the intraocular pressure (IOP) under a maximum local and oral antiglaucomatous therapy with or without additional application of local steroids. METHODS: A retrospective clinical analysis of 121 consecutive patients who underwent primary trabeculectomy for open-angle glaucoma in 2013 and who attended the outpatient clinic at least 3 weeks before surgery was carried out. The patients were set on preoperative therapy as follows: continuation of the maximum local antiglaucomatous therapy (with or without local dexamethasone 1 mg/ml 3 times daily) or administration of 750 mg acetazolamide orally per day (with or without local steroids). RESULTS: The switch to oral antiglaucomatous therapy led to a mean IOP rise of 3.14 mm Hg which was short of statistical significance (p = 0.052). The additional administration of local steroids did not significantly influence the IOP (p = 0.218). Some patients with oral acetazolamide therapy and local steroid application showed large increases in IOP up to 30 mm Hg. CONCLUSION: The mean IOP rise of 3.14 mm Hg 3 weeks after replacement of antiglaucomatous eye drops by acetazolamide was short of missing statistical significance and seems to be clinically negligible for this relatively short period. The advantages of a lower postoperative fibrotic activity have to be weighed up against this change in IOP. Surprisingly, the effect of administration of local steroids for 3 weeks was minor compared to the effect of the switch from local to oral antiglaucomatous medication. Individual major IOP increases under the preoperative therapy change should be taken into consideration.

Comprehensive assessment of food and nutrient intake of children and adolescents in Germany: EsKiMo II - the eating study as a KiGGS module.

BACKGROUND: As part of the second wave of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2), food and nutrient intake of children and adolescents aged 6-17 years living in Germany is assessed in EsKiMo II - the Eating Study as a KiGGS Module. METHODS: EsKiMo II is a cross-sectional study, conducted from June 2015 until September 2017. The study population comprises 6 to 17-year-old study participants from the cross-sectional sample of KiGGS Wave 2 in 167 KiGGS sample points, which are revisited by trained nutritionists. Dietary intake is assessed by weighted food records during three consecutive days plus one randomly selected day within the following 3 months for children aged 6-11 years. Dietary intake for adolescents aged 12-17 years is assessed by computer-assisted dietary history interviews, reflecting the past four weeks, using the software DISHES. Further information, for example, about specific diets and dietary supplement intake, is reported during a standardised computer assisted interview for all participants. Food items are coded by the German Food Code and Nutrient Database (BLS 3.02). DISCUSSION: EsKiMo II provides actual data on the dietary behaviour of children and adolescents living in Germany and their determinants. Results of EsKiMo II will be relevant for decision-making, measures, and evaluations within nutrition, consumer and health policy.

[Lymphoepithelial carcinoma of the eye]. / Lymphoepitheliales Karzinom am Auge.

A lymphoepithelial carcinoma of the conjunctiva was excised in an 80-year-old female patient. The otorhinolaryngeal (ENT) examination did not show any abnormalities and nasopharyngeal or systemic metastases were absent. A strictly controlled clinical follow-up of the excision site was scheduled. A lymphoepithelial carcinoma of the eye is very rare and it is classified under the nasopharyngeal carcinomas. The diagnostics and therapy are an interdisciplinary task involving ENT, radiology, pathology and oncology and if the tumor cannot be completely excised, radiotherapy is also included.

Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study.

PURPOSE: The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. PATIENTS AND METHODS: Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic. The RecPRAME dose was 20, 100 or 500 µg in cohorts 1, 2 and 3, respectively, with a fixed dose of AS15. Adverse events (AEs), including predefined dose-limiting toxicity (DLT) and the anti-PRAME humoral response (ELISA), were coprimary end points. Cellular immune responses were evaluated using in vitro assays. RESULTS: 66 patients were treated (20, 24 and 22 in the respective cohorts). AEs considered by the investigator to be causally related were mostly grade 1 or 2 injection site symptoms, fatigue, chills, fever and headache. Two DLTs (grade 3 brain oedema and proteinuria) were recorded in two patients in two cohorts (cohorts 2 and 3). All patients had detectable anti-PRAME antibodies after four immunisations. Percentages of patients with predefined PRAME-specific-CD4+T-cell responses after four immunisations were similar in each cohort. No CD8+ T-cell responses were detected. CONCLUSIONS: The PRAME immunotherapeutic had an acceptable safety profile and induced similar anti-PRAME-specific humoral and cellular immune responses in all cohorts. As per protocol, the phase II study segment was initiated to further evaluate the 500 µg PRAME immunotherapeutic dose. TRIAL REGISTRATION NUMBER: NCT01149343, Results.

Human alkaline phosphatases. Evidence of three isoenzymes (placental, intestinal and liver-bone-kidney-type) by lectin-binding affinity and immunological specificity.

The structural relationship between human alkaline phosphatase isoenzymes from placenta, intestine, liver, bone and kidney was investigated by lectin-binding affinity chromatography. In addition, antibody-binding sites of the enzymes were studied using monospecific antisera against each of the isoenzymes. Evidence is offered for the existence of three classes of alkaline phosphatases: the placental isoenzyme, the intestinal isoenzyme and the liver-bone-kidney-type-isoenzyme: 1. A high affinity to bind to concanavalin A and lentil lectin characterizes the placental isoenzyme in contrast to the other isoenzymes. The intestinal isoenzyme remains totally unbound. The liver-bone-kidney-isoenzyme demonstrates a microheterogeneity with bound and unbound parts. A small unbound fraction can be detected in the placental isoenzyme, also when lentil lectin is used. 2. The placental isoenzyme and the isoenzymes purified from liver, bone and kidney are bound by wheat germ lectin-Sepharose, but not the intestinal isoenzyme. All isoenzymes are eluted as a homogeneous peak. 3. Using Helix pomatia lectin-Sepharose, all isoenzymes are unreactive except a minor fraction of kidney alkaline phosphatase. 4. Antibodies to the placental isoenzyme show a partial cross-reaction with the intestinal isoenzyme, but can be obtained monospecific after absorption. 5. Antibodies to the intestinal isoenzyme show a partial cross-reaction to the placental isoenzyme, respectively, but are monospecific again after absorption. 6. Antibodies to liver, bone or kidney isoenzymes show a complete cross-reaction, but are unreactive with the placental and intestinal isoenzyme; after absorption with a heterologous isoenzyme of this group, no further reaction can be demonstrated with any of the three isoenzymes. Thus, lectin-binding affinity identifies the same isoenzyme classes by their carbohydrate parts, as antibodies presumably do by the protein parts of the isoenzymes. Furthermore, lectin-binding affinity demonstrates a microheterogeneity of the placental isoenzyme with lentil lectin-Sepharose and of the liver-bone-kidney-type-isoenzyme with different lectins.

Transient expansion of peptide-specific lymphocytes producing IFN-gamma after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage-A1/A3-positive tumors.

Assessment of T-cell activation is pivotal for evaluation of cancer immunotherapy. We initiated a clinical trial in patients with MAGE-A1 and/or -A3 tumors using autologous DC pulsed with MAGE peptides aimed at analyzing T-cell-derived, IFN-gamma secretion by cytokine flow cytometry and ELISPOT. We also tested whether further KLH addition could influence this response favorably. Monocyte-derived DC were generated from leukapheresis products. They were pulsed with the relevant MAGE peptide(s) alone in group A (n=10 pts) and additionally with KLH in group B (n=16 pts). A specific but transient increase in the number of peripheral blood T lymphocytes secreting IFN-gamma in response to the vaccine peptide(s) was observed in 6/8 patients of group A and in 6/16 patients of group B. We conclude that anti-tumor vaccination using DC pulsed with MAGE peptides induces a potent but transient anti-MAGE, IFN-gamma secretion that is not influenced by the additional delivery of a nonspecific, T-cell help.

[Drusen characteristics after internal limiting membrane peeling]. / Verhalten von Drusen nach "internal limiting membrane peeling".

BACKGROUND: There are some reports showing isolated cases of drusen regression after pars plana vitrectomy (ppV) with peeling of the internal limiting membrane (iLM). Drusen characteristics after iLM peeling was investigated in this study. PATIENTS AND METHODS: The data of 527 patients who had received iLM peeling between 2004 and 2012 were retrospectively collected and those patients with retinal drusen were selected for the study. Fundus photographs before and after vitrectomy due to a macular hole or epiretinal gliosis were compared and drusen arrangement in the peeling site was analyzed. The aim of the study was to show whether there was drusen regression 2-5 months after surgery. RESULTS: Out of the 527 patients 11 showed central macular drusen, 4 with confluent large drusen (> 63 µm diameter) and 7 with small hard drusen (≤ 63 µm diameter). One patient showed drusen regression after iLM peeling without any changes in the other eye and all other patients showed no differences in the drusen findings (n = 6) or even some additional drusen (n = 4) without drusen alterations in the other eye. CONCLUSION: The results of this study could not confirm some reports showing drusen regression after iLM peeling in the peeling site in general and there was only one single case of central drusen regression.

The majority of autologous cytolytic T-lymphocyte clones derived from peripheral blood lymphocytes of a melanoma patient recognize an antigenic peptide derived from gene Pmel17/gp100.

Anti-melanoma cytolytic T-lymphocyte (CTL) clones were derived from peripheral blood lymphocytes of HLA-A2 melanoma patient LB265 after stimulation with the autologous tumor cell line LB265-MEL, which showed high expression of melanocyte-lineage specific genes. Of 55 CTL clones, 46 recognized HLA-A2-restricted antigens. These 46 CTL clones were studied for their ability to specifically release tumor necrosis factor in the presence of COS cells cotransfected with the HLA-A2 gene and the cDNA of either tyrosinase, Melan-A/MART1, Pmel17/gpl00, gp75/TRP1, or MSH receptor. Six CTL clones recognized the Melan-A/MART1 antigen, whereas the remaining 40 CTL clones recognized a Pmel17/gp100 antigen. These 40 anti-PmelI7/gpl00 CTL clones were all able to lyse T2 cells pulsed with the antigenic peptide YLEPGPVTA, as previously reported. The T-cell receptor beta chain hypervariable region was sequenced and found to be identical in the 15 CTL clones analyzed. Taken together, these data show a high frequency of Pmell7/gp100-specific T cells in autologous antitumor CTL clones derived from peripheral blood of a melanoma patient.

The EORTC and drug development. European Organisation for Research and Treatment of Cancer.

Early drug development at EORTC has always been subject to structural changes to adapt to the rapid changes that occur in oncological drug development. The expertise of early drug developers has always been cross-fertilised with disease-/tumour-oriented groups and also backwards to the laboratory research groups. This results in the establishment of a solid and dedicated network of medical oncologists with focused expertise in cancer drug development. The EORTC Data Center is fully equipped with all expertise to support clinical research activities and includes regulatory, safety, and quality assurance desks. The EORTC New Drug development Programme (NDDP) provides methodological expertise to early clinical trials and coordinates phase I and phase II studies addressing various approaches. Through NDDP, the early clinical groups and the disease-/tumour-oriented groups have created specific networks to address early drug development in specific tumour types. This results in very efficient networks which have the resources and the patients to address and conduct challenging clinical trials in a standardised fashion ensuring the highest standards in cancer treatment.