Known unknowns: building an ethics of uncertainty into genomic medicine

Background Genomic testing has reached the point where, technically at least, it can be cheaper to undertake panel-, exome- or whole genome testing than it is to sequence a single gene. An attribute of these approaches is that information gleaned will often have uncertain significance. In addition to the challenges this presents for pre-test counseling and informed consent, a further consideration emerges over how - ethically - we should conceive of and respond to this uncertainty. To date, the ethical aspects of uncertainty in genomics have remained under-explored. Discussion In this paper, we draft a conceptual and ethical response to the question of how to conceive of and respond to uncertainty in genomic medicine. After introducing the problem, we articulate a concept of ‘genomic uncertainty’. Drawing on this, together with exemplar clinical cases and related empirical literature, we then critique the presumption that uncertainty is always problematic and something to be avoided, or eradicated. We conclude by outlining an ‘ethics of genomic uncertainty’; describing how we might handle uncertainty in genomic medicine. This involves fostering resilience, welfare, autonomy and solidarity. Conclusions Uncertainty will be an inherent aspect of clinical practice in genomics for some time to come. Genomic testing should not be offered with the explicit aim to reduce uncertainty. Rather, uncertainty should be appraised, adapted to and communicated about as part of the process of offering and providing genomic information. Keywords Ethics Uncertainty Genomics Clinical genomics Massively parallel sequencing Genome sequencing Genomic testing Genetic counseling Rare diseases Variants of uncertain significanc

Imaging Sources with Fast and Slow Emission Components

We investigate two-proton correlation functions for reactions in which fast dynamical and slow evaporative proton emission are both present. In such cases, the width of the correlation peak provides the most reliable information about the source size of the fast dynamical component. The maximum of the correlation function is sensitive to the relative yields from the slow and fast emission components. Numerically inverting the correlation function allows one to accurately disentangle fast dynamical from slow evaporative emission and extract details of the shape of the two-proton source.Comment: 13 pages, 4 figure

Breakup Density in Spectator Fragmentation

Proton-proton correlations and correlations of protons, deuterons and tritons with alpha particles from spectator decays following 197Au + 197Au collisions at 1000 MeV per nucleon have been measured with two highly efficient detector hodoscopes. The constructed correlation functions, interpreted within the approximation of a simultaneous volume decay, indicate a moderate expansion and low breakup densities, similar to assumptions made in statistical multifragmentation models. PACS numbers: 25.70.Pq, 21.65.+f, 25.70.Mn, 25.75.GzComment: 11 pages, LaTeX with 3 included figures; Also available from http://www-kp3.gsi.de/www/kp3/aladin_publications.htm

A Kinematically Complete Measurement of the Proton Structure Function F2 in the Resonance Region and Evaluation of Its Moments

We measured the inclusive electron-proton cross section in the nucleon resonance region (W < 2.5 GeV) at momentum transfers Q**2 below 4.5 (GeV/c)**2 with the CLAS detector. The large acceptance of CLAS allowed for the first time the measurement of the cross section in a large, contiguous two-dimensional range of Q**2 and x, making it possible to perform an integration of the data at fixed Q**2 over the whole significant x-interval. From these data we extracted the structure function F2 and, by including other world data, we studied the Q**2 evolution of its moments, Mn(Q**2), in order to estimate higher twist contributions. The small statistical and systematic uncertainties of the CLAS data allow a precise extraction of the higher twists and demand significant improvements in theoretical predictions for a meaningful comparison with new experimental results.Comment: revtex4 18 pp., 12 figure

Tensor Polarization of the phi meson Photoproduced at High t

As part of a measurement of the cross section of $\phi$ meson photoproduction to high momentum transfer, we measured the polar angular decay distribution of the outgoing $K^+$ in the channel $\phi \to K^+K^-$ in the $\phi$ center-of-mass frame (the helicity frame). We find that s-channel helicity conservation (SCHC) holds in the kinematical range where $t$-channel exchange dominates (up to $-t \sim 2.5$ GeV$^2$ for $E_{\gamma}$=3.6 GeV). Above this momentum, $u$-channel production of a $\phi$ meson dominates and induces a violation of SCHC. The deduced value of the $\phi NN$ coupling constant lies in the upper range of previously reported values.Comment: 6 pages; 5 figure

Exclusive ρ0\rho^0 meson electroproduction from hydrogen at CLAS

The longitudinal and transverse components of the cross section for the $e p\to e^\prime p \rho^0$ reaction were measured in Hall B at Jefferson Laboratory using the CLAS detector. The data were taken with a 4.247 GeV electron beam and were analyzed in a range of $x_B$ from 0.2 to 0.6 and of $Q^2$ from 1.5 to 3.0 GeV$^2$. The data are compared to a Regge model based on effective hadronic degrees of freedom and to a calculation based on Generalized Parton Distributions. It is found that the transverse part of the cross section is well described by the former approach while the longitudinal part can be reproduced by the latter.Comment: 6 pages, 4 figure

Nuclear temperature measurements with helium isotopes

Temperatures extracted with the family of (He-3, He-4) isotope ratio thermometers, T-He, have been studied and cross-checked with temperatures, T(He-4*) constructed from excited and ground state populations of He-4. Empirical correction factors provide baseline corrections for sequential decay effects for T-He < 4.5 MeV, independent of projectile, target and incident energies. After corrections for fluctuations due to sequential decay, statistical calculations predict that T-He, and T(He-4*) should agree. (C) 1998 Published by Elsevier Science B.V. All rights reserved