Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Overview of JET results

Since the last IAEA conference, the scientific programme of JET has focused on the qualification of the integrated operating scenarios for ITER and on physics issues essential for the consolidation of design choices and the efficient exploitation of ITER. Particular attention has been given to the characterization of the edge plasma, pedestal energy and edge localized modes (ELMs), and their impact on plasma facing components (PFCs). Various ELM mitigation techniques have been assessed for all ITER operating scenarios using active methods such as resonant magnetic field perturbation, rapid variation of the radial field and pellet pacing. In particular, the amplitude and frequency of type I ELMs have been actively controlled over a wide parameter range (q95 = 3-4.8, βN ≥ 3.0) by adjusting the amplitude of the n = 1 external perturbation field induced by error field correction coils. The study of disruption induced heat loads on PFCs has taken advantage of a new wide-angle viewing infrared system and a fast bolometer to provide a detailed account of time, localization and form of the energy deposition. Specific ITER-relevant studies have used the unique JET capability of varying the toroidal field (TF) ripple from its normal low value δBT = 0.08% up to δBT = 1% to study the effect of TF ripple on high confinement-mode plasmas. The results suggest that δBT < 0.5% is required on ITER to maintain adequate confinement to allow QDT = 10 at full field. Physics issues of direct relevance to ITER include heat and toroidal momentum transport, with experiments using power modulation to decouple power input and torque to achieve first experimental evidence of inward momentum pinch in JET and determine the threshold for ion temperature gradient driven modes. Within the longer term JET programme in support of ITER, activities aiming at the modification of the JET first wall and divertor and the upgrade of the neutral beam and plasma control systems are being conducted. The procurement of all components will be completed by 2009 with the shutdown for the installation of the beryllium wall and tungsten divertor extending from summer 2009 to summer 2010

Overview of JET results

Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower \u3c1 17 and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower \u3c1 17 and \u3bd 17 and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with 3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95 values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2MWm 122) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling