Direct Photon Production in 158 AGeV Pb+Pb Collisions

A measurement of direct photon production in Pb+Pb collisions at 158 AGeV has been carried out in the CERN WA98 experiment. The invariant yield of direct photons in central collisions is extracted as a function of transverse momentum in the interval 0.5 < pT < 4 GeV/c. A significant direct photon signal, compared to statistical and systematical errors, is seen at pT > 1.5 GeV/c. The results constitute the first observation of direct photons in ultrarelativistic heavy-ion collisions which could be significant for diagnosis of quark gluon plasma formation.Comment: Talk presented at Nucleus-Nucleus 2000, Strasbourg, Franc

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.Peer reviewe

Guidance document fo the Scientific Panel on Genetically Modified Organisms for the risk assessment of genetically modified microorganisms and their derived products intended for food and feed use

EFSA Journa

Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial

BACKGROUND: Tisotumab vedotin is a first-in-human antibody–drug conjugate directed against tissue factor, which is expressed across multiple solid tumour types and is associated with poor clinical outcomes. We aimed to establish the safety, tolerability, pharmacokinetic profile, and antitumour activity of tisotumab vedotin in a mixed population of patients with locally advanced or metastatic (or both) solid tumours known to express tissue factor. // METHODS: InnovaTV 201 is a phase 1–2, open-label, dose-escalation and dose-expansion study done at 21 centres in the USA and Europe. Patients (aged ≥18 years) had relapsed, advanced, or metastatic cancer of the ovary, cervix, endometrium, bladder, prostate, oesophagus, squamous cell carcinoma of the head and neck or non-small-cell lung cancer; an Eastern Cooperative Oncology Group performance status of 0–1; and had relapsed after or were not eligible to receive the available standard of care. No specific tissue factor expression level was required for inclusion. In the dose-escalation phase, patients were treated with tisotumab vedotin between 0·3 and 2·2 mg/kg intravenously once every 3 weeks in a traditional 3 + 3 design. In the dose-expansion phase, patients were treated at the recommended phase 2 dose. The primary endpoint was the incidence of adverse events, including serious adverse events, infusion-related, treatment-related and those of grade 3 or worse, and study drug-related adverse events, analysed in all patients who received at least one dose of tisotumab vedotin (full analysis population). This trial is registered with ClinicalTrials.gov, number NCT02001623, and is closed to new participants with follow-up ongoing. // FINDINGS: Between Dec 9, 2013, and May 18, 2015, 27 eligible patients were enrolled to the dose-escalation phase. Dose-limiting toxicities, including grade 3 type 2 diabetes mellitus, mucositis, and neutropenic fever, were seen at the 2·2 mg/kg dose; therefore, 2·0 mg/kg of tisotumab vedotin intravenously once every 3 weeks was established as the recommended phase 2 dose. Between Oct 8, 2015, and April 26, 2018, 147 eligible patients were enrolled to the dose-expansion phase. The most common (in ≥20% of patients) treatment-emergent adverse events of any grade were epistaxis (102 [69%] of 147 patients), fatigue (82 [56%]), nausea (77 [52%]), alopecia (64 [44%]), conjunctivitis (63 [43%]), decreased appetite (53 [36%]), constipation (52 [35%]), diarrhoea (44 [30%]), vomiting (42 [29%]), peripheral neuropathy (33 [22%]), dry eye (32 [22%]), and abdominal pain (30 [20%]). The most common adverse events of grade 3 or worse were fatigue (14 [10%] of 147 patients), anaemia (eight [5%]), abdominal pain (six [4%]), hypokalaemia (six [4%]), conjunctivitis (five [3%]), hyponatraemia (five [3%]), and vomiting (five [3%]). 67 (46%) of 147 patients had a treatment-emergent serious adverse event. 39 (27%) of 147 patients had a treatment-emergent serious adverse event related to the study drug. Infusion-related reactions occurred in 17 (12%) of 147 patients. Across tumour types, the confirmed proportion of patients who achieved an objective response was 15·6% (95% CI 10·2–22·5; 23 of 147 patients). There were nine deaths across all study phases (three in the dose-escalation phase and six in the dose-expansion phase); only one case of pneumonia in the dose-expansion phase was considered possibly related to study treatment. // INTERPRETATIONS: Tisotumab vedotin has a manageable safety profile with encouraging preliminary antitumour activity across multiple tumour types in heavily pretreated patients. Continued evaluation of tisotumab vedotin is warranted in solid tumours. // FUNDING: Genmab A/S

IEA Wind TCP Task 29, Phase IV: Detailed Aerodynamics of Wind Turbines

International audienceThis report describes the final results of the fourth phase of IEA TCP Wind Task 29. The project period of this fourth phase was from January 1 st 2018 until December 31 st 2020. It was the follow-up of three former IEA Task 29 phases (often denoted as Mexnext-I to Mexnext-III). In all phases wind turbine aerodynamic models were validated and improved with detailed aerodynamic measurements. In these detailed aerodynamic experiments pressure distributions at different locations along the rotor blades are measured anyhow where measurements of e.g. inflow velocities and boundary layer transition are very nice to know. The first three phases were mainly built around wind tunnel measurements on a small scale wind turbine with rotor diameter of 4.5 meter from the (New) Mexico project but the present phase was built around field measurements from the DanAero experiment.This DanAero experiment was carried out at atmospheric field conditions on a 2MW turbine by Danish Technical University DTU and 4 industrial partners (LM Glassfiber, Siemens WindPower, Vestas and Dong Energy) in 2 periods from 2007 until 2010 and from 2010 until 2013. Amongst others surface pressures and inflow velocities were measured at four sections along a blade and a row of surface flush mounted microphones was installed at the outer part ofthe blade. In IEA Task29 Phase IV the DanAero data were made available to the IEA Task 29 participants which enabled a detailed analysis in a collaborative action. Amongst others a critical scrutinising of data took place with subsequent further improvement of measurement quality. Moreover the measurements were used as validation material for the many design models which are available in the consortium. A wide variety of models could be considered ranging from high fidelity (but time consuming) CFD to lower fidelity but efficient engineering models. Intermediate methods (e.g. free wake methods) were applied as well. Several calculational rounds were carried out where calculations were compared with measurements. Amongst others a case was defined at simple steady and axi-symmetric conditions close to a measurement case with little shear and little yaw but also measurement cases at high yaw and high shear were simulated. Moreover the level of detail from the DanAero experiment allowed an in-depth analysis of several wind turbine aerodynamic aspects, e.g. Aerodynamic response to turbulent inflow; Sheared inflow; 2D/3D aerodynamics;Aeroelastic effectsTransition characteristics in realistic flow conditions;Acoustics. The project was carried out by a consortium which consisted of research groups and industries from 9 different countries China: Chinese Wind Energy Association, CWEA Denmark: Technical University of Denmark, DTU, Siemens-Gamesa Renewable Energy France: IFPEn, LHEEA lab - Centrale Nantes/CNRS, ONERA, EDFGermany: ForWind/Fraunhofer IWES, Kiel University of Applied Sciences, University of Stuttgart, WindNovation, Enercon Deutsches Zentrum für Luft- und Raumfahrt e.V., DLR University of Applied Sciences EmdenItaly: PoliMi, RSE, CNR - INMNetherlands: TNO Energy Transition (formerly ECN, Operating Agent), Delft University of Technology, TUDelft, DNV-GL Suzlon Blade Technology, SBT, CWI, LM and University of Twente, UTwenteItaly: PoliMi, RSE, CNR - INMSweden: Uppsala University, Campus GotlandSwitzerland: UAS RapperswilUSA: National Renewable Energy Laboratory, NREL</ul

Oral interferon beta-1a in relapsing-remitting multiple sclerosis: A double-blind randomized study

Background: Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. Methods: In this multicenter, double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. Results: Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. Conclusion: Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated