The right to die in the minimally conscious state

The right to die has for decades been recognised for persons in a vegetative state, but there remains controversy about ending life-sustaining medical treatment for persons in the minimally conscious state (MCS). The controversy is rooted in assumptions about the moral significance of consciousness, and the value of life for patients who are conscious and not terminally ill. This paper evaluates these assumptions in light of evidence that generates concerns about quality of life in the MCS. It is argued that surrogates should be permitted to make decisions to withdraw life-sustaining medical treatment from patients in the MCS.     

The quantitative analysis of D2-dopamine receptors in baboon striatum in vivo with 3-N-[2'-18F]fluoroethylspiperone using positron emission tomography

We used the ligand 3-N-[2'-18F]fluoroethylspiperone (FESP), which binds to D2-dopamine receptors in the striatum, and positron emission tomography (PET) to quantify striatal D2-dopamine densities (Bmax) and binding kinetics in baboon brain in vivo. Sequential PET scans were obtained for 4 h post injection. Various similar models based on a nonlinear kinetic four-compartment model that takes into account the effect of ligand specific activity were used. We investigated the effect of exact model configuration on the reliability of Bmax and other kinetic transfer coefficients. We found that with the ligand FESP and dynamic PET studies, the estimated values of Bmax and other model parameters are sensitive to the choice of model configuration, ligand specific activity, and data analysis technique. The limitations of the reliability of parameter estimates in a complex kinetic model for receptor ligands were studied in simulation calculations. Results showed that the accuracy of estimated values of Bmax is affected by both the ligand binding properties and the injected dose of ligand. The estimated average value of kinetic model parameters was as follows: ligand-receptor dissociation constant k4 = 0.0080 min-1; the product of ligand-receptor association constant and fraction of ligand available to bind to specific receptors f2ka = 0.0052 (min nM)-1; and D2-dopamine receptor density Bmax = 37.5 pmol g-1.     

Quantification of baboon cortical S2 serotonin receptors in vivo with 3-N-(2′-Fl8)fluoroethylspiperone and positron emission tomography

We used the ligand 3-N-(2-F 18)fluoroethylspiperone (FESP) and positron emission tomography (PET) to quantify in vivo serotonin S₂ neuroreceptor density and affinity in the baboon frontal cortex. In the cortex, FESP binds specifically and exclusively to S₂ receptors, and an equilibrium is reached when the rate of ligand-receptor association and dissociation become equal. Using multiple studies in the same baboon, an equilibrium (saturation) analysis approach provided a linear Hill plot with a slope of 1.02 (r ² =0.988,P <0.0001), indicative of ligand binding to a single receptor class. Using serial PET scans, a dynamic approach was also used to quantify S₂ receptors in the frontal cortex of the baboon, which provided an estimate of receptor densityB _max =35.6 ± 10.9 pmol/g. The rate constants corresponding to transport into and out of tissue wereK _* ¹ = 0.2720 ± 0.0299 mol/min g andk _* ² = 0.0786 ± 0.0315 min^–1, respectively. The ligand-receptor dissociation constant wask _* ⁴ = 0.0154 ± 0.0109 min^–1.     

Mutation analysis of 24 known cancer genes in the NCI-60 cell line set

The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.     

Minimisation of parameter estimation errors in dynamic PET: choice of scanning schedules

We addressed the general problem of finding an optimal scan schedule in positron emission tomography (PET) dynamic studies which minimises the errors in estimating the transfer constants between a set of compartments. As an example, the influence of scan intervals in PET on the accuracy of estimation of the rate constants and vascular component in the deoxyglucose method was examined using an empirical noise model. The simulated noisy curves used in the analysis were compared with patient data to validate the noise model. A series of scan schedules were compared for accuracy of fit by evaluating the determinant of the variance-covariance matrix of the fitted parameters as an index of parameter accuracy. For realistic noise levels there is a monotonic improvement in the index of parameter accuracy with increasing sampling frequency, particularly over the initial minutes after the tracer injection. However, since faster schedules are more susceptible to errors introduced by time mismatches between plasma and tissue curves and impose greater computational and memory overhead, an initial scan duration of 30 s provide a practical trade-off for dynamic PET 18F-fluoro-deoxyglucose studies.     

The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

1. Download high-res image (321KB)
2. Download full-size image

     

The phenomenology of reactivated trauma memories in older adults: a preliminary study

Empirical literature concerning reactivated memories of trauma among older adults is sparse. Twelve elderly participants with re-emergent, involuntary, memories of previous adversity were given a structured interview exploring phenomenological aspects of the experience. Intense and highly vivid sensory components of memory were common as was a sense of current threat. This was compared with data available from the adult literature on post-traumatic stress disorder (PTSD) and we conclude that the process of trauma memory reactivation after years of attenuation seems not to have affected involuntary intrusive representations of what happened. Recommendations to extend the current research are suggested.