Genetic stratification of inherited and sporadic phaeochromocytoma and paraganglioma: implications for precision medicine.

Over the past two decades advances in genomic technologies have transformed knowledge of the genetic basis of phaeochromocytoma and paraganglioma (PPGL). Though traditional teaching suggested that inherited cases accounted for only 10% of all phaeochromocytoma diagnosis, current estimates are at least three times this proportion. Inherited PPGL is a highly genetically heterogeneous disorder but the most frequently results from inactivating variants in genes encoding subunits of succinate dehydrogenase. Expanding knowledge of the genetics of PPGL has been translated into clinical practice by the provision of widespread testing for inherited PPGL. In this review, we explore how the molecular stratification of PPGL is being utilized to enable more personalized strategies for investigation, surveillance and management of affected individuals and their families. Translating recent genetic research advances into clinical service can not only bring benefits through more accurate diagnosis and risk prediction but also challenges when there is a suboptimal evidence base for the clinical consequences or significance of rare genotypes. In such cases, clinical, biochemical, pathological and functional imaging assessments can all contribute to more accurate interpretation and clinical management.We apologise to all the authors whose work we were unable to cite because of space constraints. We thank Dr Birke Bausch, University of Freiburg, Germany and Anna Roslyakowa, Department of Surgery, Endocrinology Research Center, Moscow, Russia for their expert input. RC acknowledges support from AMEND and GIST Support UK. ERM acknowledges support from European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre) and Cancer Research UK Cambridge Cancer Centre. The views expressed are those of the authors and not necessarily those of the NHS or NIHR. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve

Spin-flip and spin-conserving optical transitions of the nitrogen-vacancy centre in diamond

We map out the first excited state sublevel structure of single nitrogen-vacancy (NV) colour centres in diamond. The excited state is an orbital doublet where one branch supports an efficient cycling transition, while the other can simultaneously support fully allowed optical Raman spin-flip transitions. This is crucial for the success of many recently proposed quantum information applications of the NV defects. We further find that an external electric field can be used to completely control the optical properties of a single centre. Finally, a group theoretical model is developed that explains the observations and provides good physical understanding of the excited state structure

The XMM-Newton Ω\Omega Project

The abundance of high-redshift galaxy clusters depends sensitively on the matter density \OmM and, to a lesser extent, on the cosmological constant $\Lambda$. Measurements of this abundance therefore constrain these fundamental cosmological parameters, and in a manner independent and complementary to other methods, such as observations of the cosmic microwave background and distance measurements. Cluster abundance is best measured by the X-ray temperature function, as opposed to luminosity, because temperature and mass are tightly correlated, as demonstrated by numerical simulations. Taking advantage of the sensitivity of XMM-Newton, our Guaranteed Time program aims at measuring the temperature of the highest redshift (z>0.4) SHARC clusters, with the ultimate goal of constraining both \OmM and $\Lambda$.Comment: To appear in the Proceedings of the XXI Moriond Conference: Galaxy Clusters and the High Redshift Universe Observed in X-rays, edited by D. Neumann, F. Durret, & J. Tran Thanh Va

Ion impact induced Interatomic Coulombic Decay in neon and argon dimers

We investigate the contribution of Interatomic Coulombic Decay induced by ion impact in neon and argon dimers (Ne$_2$ and Ar$_2$) to the production of low energy electrons. Our experiments cover a broad range of perturbation strengths and reaction channels. We use 11.37 MeV/u S$^{14+}$, 0.125 MeV/u He$^{1+}$, 0.1625 MeV/u He$^{1+}$ and 0.150 MeV/u He$^{2+}$ as projectiles and study ionization, single and double electron transfer to the projectile as well as projectile electron loss processes. The application of a COLTRIMS reaction microscope enables us to retrieve the three-dimensional momentum vectors of the ion pairs of the fragmenting dimer into Ne$^{q+}$/Ne$^{1+}$ and Ar$^{q+}$/Ar$^{1+}$ (q = 1, 2, 3) in coincidence with at least one emitted electron

Can a falling tree make a noise in two forests at the same time?

It is a commonplace to claim that quantum mechanics supports the old idea that a tree falling in a forest makes no sound unless there is a listener present. In fact, this conclusion is far from obvious. Furthermore, if a tunnelling particle is observed in the barrier region, it collapses to a state in which it is no longer tunnelling. Does this imply that while tunnelling, the particle can not have any physical effects? I argue that this is not the case, and moreover, speculate that it may be possible for a particle to have effects on two spacelike separate apparatuses simultaneously. I discuss the measurable consequences of such a feat, and speculate about possible statistical tests which could distinguish this view of quantum mechanics from a ``corpuscular'' one. Brief remarks are made about an experiment underway at Toronto to investigate these issues.Comment: 9 pp, Latex, 3 figs, to appear in Proc. Obsc. Unr. Conf.; Fig 2 postscript repaired on 26.10.9

On Uniqueness of the Jump Process in Quantum Measurement Theory

We prove that, contrary to the standard quantum theory of continuous observation, in the formalism of Event Enhanced Quantum Theory the stochastic process generating individual sample histories of pairs (observed quantum system, observing classical apparatus) is unique. This result gives a rigorous basis to the previous heuristic argument of Blanchard and Jadczyk. Possible implications of this result are discussed.Comment: 31 pages, LaTeX, article; e-mail contact [email protected]

Aspherical galaxy clusters: effects on cluster masses and gas mass fractions

We present an investigation of the effects of asphericity on the estimates of total mass and gas mass fraction in galaxy clusters from X-ray observations. We model the aspherical shape of galaxy clusters by a triaxial model and compare the true total mass and the true total gas mass fraction with the corresponding quantities obtained with the assumption of spherical symmetry. In the triaxial model we allow the extent along the line of sight to vary in order to describe elongated and compressed cluster shapes. Using a sample of 10 ROSAT clusters and a recent CHANDRA observation we find the following results. For prolate or oblate shapes the difference between triaxial and spherical model both in the mass and in the gas mass fraction are negligible (less than 3 %). For more aspherical shapes the total mass is underestimated (overestimated) in the centre, if the cluster is compressed (elongated). The gas mass fraction is overestimated for compressed clusters and slightly underestimated for elongated clusters. Comparing X-ray masses with gravitational lensing estimates, we find that elongations along the line of sight can resolve discrepancies of masses determined by the two different methods of up to ~30 %. The combination of Sunyaev-Zel'dovich and X-ray observations is useful to measure the elongation of the cluster along the line of sight. As an application, we estimate the elongation of the cluster CL0016+16 with two different approaches, Sunyaev-Zel'dovich measurements and comparison of weak lensing and X-ray masses, and find reasonable agreement.Comment: Accepted for publication in A&A, 9 pages, 5 figure

Classical interventions in quantum systems. I. The measuring process

The measuring process is an external intervention in the dynamics of a quantum system. It involves a unitary interaction of that system with a measuring apparatus, a further interaction of both with an unknown environment causing decoherence, and then the deletion of a subsystem. This description of the measuring process is a substantial generalization of current models in quantum measurement theory. In particular, no ancilla is needed. The final result is represented by a completely positive map of the quantum state $\rho$ (possibly with a change of the dimensions of $\rho$). A continuous limit of the above process leads to Lindblad's equation for the quantum dynamical semigroup.Comment: Final version, 14 pages LaTe

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I–III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies