Safety, tolerability and clinical implementation of 'ready-to-use' 68gallium-DOTA0-Tyr3-octreotide (68Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)

BACKGROUND: 68Ga-DOTA0-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography-CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT-CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of 68Ga-DOTATOC using a new 'ready-to-use' 68Ga-DOTATOC formulation for injection has been developed (68Ga-DOTATOC (SomaKIT TOC)). OBJECTIVES: This study aimed to assess the safety and tolerability of 68Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service. METHODS: A first-in-human phase I/II multicentre, open-label study of a single dose of 68Ga-DOTATOC (SomaKIT TOC) 2 MBq/kg±10% (range 100-200 MBq) in patients with biopsy-proven grade 1-2 GEP-NETs. PET-CT was performed post injection. Patients were followed up for 28 days. We next implemented this new synthesis methodology in a clinical service assessed over 11 months. RESULTS: Twenty consenting patients were recruited; 14 males, 6 females; mean (SD) age 58 years (12); NET grade 1 (70%), grade 2 (30%); and 75% with stage IV disease. Twelve patients experienced at least one adverse event (AE) during the study with no grade 3-4 toxicities. Only four AEs were classified as possibly (headache (n=1; 4%), nausea (1; 4%)) or probably (dysgeusia (1; 4%), paraesthesia (1; 4%)) related to the study preparation. One hundred thirteen vials of 68Ga-DOTATOC (SomaKIT TOC) were synthesised with the 'kit' over a period of 11 months for clinical utility. Only 2/113 vials (1.77%) were rejected. CONCLUSIONS: The new ready-to-use preparation of 68Ga-DOTATOC (SomaKIT TOC) for injection was safe and well tolerated. This has led to the world's first (EMA) licensed 68Ga-DOTATOC (SomaKIT TOC) radiopharmaceutical for the utility of PET imaging in patients with NETs. This preparation can be robustly implemented into routine clinical practice

Dynamics of a small neutrally buoyant sphere in a fluid and targeting in Hamiltonian systems

We show that, even in the most favorable case, the motion of a small spherical tracer suspended in a fluid of the same density may differ from the corresponding motion of an ideal passive particle. We demonstrate furthermore how its dynamics may be applied to target trajectories in Hamiltonian systems.Comment: See home page http://lec.ugr.es/~julya

Bailout Embeddings and Neutrally Buoyant Particles in Three-Dimensional Flows

We use the bailout embeddings of three-dimensional volume-preserving maps to study qualitatively the dy- namics of small spherical neutrally buoyant impurities suspended in a time-periodic incompressible fluid flow. The accumulation of impurities in tubular vortical structures, the detachment of particles from fluid trajectories near hyperbolic invariant lines, and the formation of nontrivial three-dimensional structures in the distribution of particles are predicted.Comment: 4 pages, 3 figure

Emergent global oscillations in heterogeneous excitable media: The example of pancreatic beta cells

Using the standard van der Pol-FitzHugh-Nagumo excitable medium model I demonstrate a novel generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable beta cells, quiescent when isolated, are found to oscillate when coupled despite the absence of a pacemaker region.Comment: See home page http://lec.ugr.es/~julya

Educational supervision and the impact of workplace-based assessments: a survey of psychiatry trainees and their supervisors

<p>Abstract</p> <p>Background</p> <p>Educational supervision (ES) is considered to be an essential component of basic specialist training in psychiatry in the UK. However, previous studies have indicated variation in its provision, and uncertainty about structure and content. Workplace-based assessments (WPBAs) were introduced in 2007 as part of major postgraduate medical training reform. Placing considerable time demands on trainees and supervisors alike, the extent to which WPBAs should utilise ES time has not been specified. As ES and WPBAs have discrete (although complementary) functions, there is the potential for this increased emphasis on assessment to displace other educational needs.</p> <p>Methods</p> <p>All junior doctors and their educational supervisors in one UK psychiatry training scheme were surveyed both before and after the introduction of WPBAs. Frequency and duration of ES were established, and structure, content and process were ascertained. Opinions on usefulness and responsibility were sought. The usage of ES for WPBAs was also assessed.</p> <p>Results</p> <p>The response rate of 70% showed general agreement between trainees and supervisors, but some significant discrepancies. Around 60% reported 1 hour of ES taking place weekly or 3 times per month. Most agreed that responsibility for ES should be shared equally between trainees and supervisors, and ES was largely seen as useful. Around 50% of trainees and supervisors used 25–50% of ES time for WPBAs, and this did not appear to affect the usefulness of ES or the range of issues covered.</p> <p>Conclusion</p> <p>ES continues to be an important component of psychiatric training. However, using ES for WPBAs introduces the potential for tension between trainees' education and their assessment by emphasising certain training issues at the expense of others. The impact of reduced training time, WPBAs and uncertainties over ES structure and content should be monitored to ensure that its benefits are maximised by remaining tailored to individual trainees' needs.</p

Ice structures, patterns, and processes: A view across the ice-fields

We look ahead from the frontiers of research on ice dynamics in its broadest sense; on the structures of ice, the patterns or morphologies it may assume, and the physical and chemical processes in which it is involved. We highlight open questions in the various fields of ice research in nature; ranging from terrestrial and oceanic ice on Earth, to ice in the atmosphere, to ice on other solar system bodies and in interstellar space