Pharmacogenetics: ethical issues and policy options

Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent, (4) availability of drugs, (5) access, and (6) clinicians' changing responsibilities in the era of pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them.     

Ethical dilemmas in testing for late onset conditions: reactions to testing and perceived impact on other family members

This paper examines some of the ethical dilemmas that arise when testing for the late onset, untreatable condition of Huntington disease (HD) specifically now that technology allows us to test younger generations of the family for the mutant gene. Drawing on interview data from families with Huntington disease, the reactions to testing and perceived impact on other family members are considered. These are discussed in the light of the possible lowering of the age of test applicants. This potentially raises problems for a younger generation as they are confronted with reproductive decisions that the older generation did not have to face. It also means that individuals have the prospect of living with knowledge of a future illness for much longer.     

The contextual modulation of conditioned taste aversions by the physical environment and time of day is similar

In a pair of experiments, we have compared the ability of changes of place (Exp. 1) and changes of time of day (Exp. 2) to separately modulate learned saline-aversion memory phenomena in rats. Neither a spatial nor a temporal change disrupted latent inhibition using the present behavioral procedure. However, pre-exposure to the taste increased the contextual control of the learned aversion expression. The aversion reappeared in the place or at the time of conditioning after extinction in a different context. The results indicate that environmental and temporal contexts can independently, but similarly modulate taste aversion learning.     

Sleep-dependent hippocampal slow activity correlates with waking memory performance in humans

The positive effect of postlearning sleep on memory consolidation as well as the relationship between sleep-related memory processes and the hippocampal formation are increasingly clarified topics in neurobiology. However, the possibility of a stable relationship between waking mnemonic performance and sleep-dependent hippocampal electric activity is unexplored. Here we report a correlative analysis between sleep-dependent parahippocampal-hippocampal (pHip-Hip) electric activity recorded by foramen ovale (FO) electrodes and different types of memory performances in epileptic patients. Psychological testing was performed days or weeks before electrophysiological recordings. The relative spectral power of the slow activity (below 1.25 Hz) during deep non-REM (NREM) sleep at the right pHip-Hip region correlated positively with the visual memory performance according to Rey-Osterrieth Complex Figure Test (ROCFT). Along the posterior-anterior direction of the hippocampal formation a linear increasing of correlations was observed. The relative power of the activity below 1.25 Hz at the left pHip-Hip during phasic REM sleep correlated positively with verbal learning performance and mnemonic retention values according to ROCFT. It is concluded that the pHip-Hip structures' capacity of producing high amplitude and synchronized slow (< 1 Hz) oscillation during deep NREM sleep is related to the functional power of these structures. We hypothesize that the asymmetric (side-specific) propagation of ponto-geniculo-occipital (PGO) activity to the pHip-Hip region is related to the memory correlates of phasic REM sleep.     

RAP: a new framework for visual categorization

Cognitive science might almost be defined as several disciplines communicating their different perspectives on the mind, the common object of study. However, domain-specific concepts and techniques can prevent, rather than foster, a communication of viewpoints. In this article, we develop a new framework for visual categorization in which the interaction between Represented (R) information and Available (A) information determine the Potent (P) information (symbolically, R ? A approximately P). We argue and illustrate that this framework helps to establish a common language to articulate issues common to low-, mid-, and high-level vision. More importantly, we present new techniques with which to visualize the so-far elusive constructs of representation and potent information.     

Effects of normal aging and Alzheimer's disease on emotional memory

Recall is typically better for emotional than for neutral stimuli. This enhancement is believed to rely on limbic regions. Memory is also better for neutral stimuli embedded in an emotional context. The neural substrate supporting this effect has not been thoroughly investigated but may include frontal lobe, as well as limbic circuits. Alzheimer's disease (AD) results in atrophy of limbic structures, whereas normal aging relatively spares limbic regions but affects prefrontal areas. The authors hypothesized that AD would reduce all enhancement effects, whereas aging would disproportionately affect enhancement based on emotional context. The results confirmed the authors' hypotheses: Young and older adults, but not AD patients, showed better memory for emotional versus neutral pictures and words. Older adults and AD patients showed no benefit from emotional context, whereas young adults remembered more items embedded in an emotional versus neutral context.     

Neuropsychological correlates of recollection and familiarity in normal aging

The dual-process model of recognition memory proposed by Jacoby (1991; see also Mandler, 1980) postulates the existence of two independent components of recognition memory: a conscious retrieval process (recollection) and an automatic component ( familiarity). Older adults appear to be impaired in recollection, but findings with respect to familiarity have been mixed. Studies of the brain bases of these components, using neurological patients, have also been inconclusive. We examined recollection and familiarity, using the process dissociation procedure, in older adults characterized on the basis of both their frontal and their medial temporal lobe function. Findings suggest that only some older adults, depending on their neuropsychological status, are impaired in recollection and/or familiarity: Recollection seems to involve both frontal and medial temporal lobe function, whereas familiarity appears to be dependent only on function associated with the medial temporal lobes.     

Review of quantity and types of spirituality research in three health care databases (1962-1999): implications for the health care ministry

Using computer technology to identify the term "spiritual," these researchers present results of the 2306 citations and compare five criteria discovered with research reported in four pastoral counseling journals. The authors note the limitations of such a search and the possible implications of the findings for health care ministry.     

On Modal Logics Characterized by Models with Relative Accessibility Relations: Part I

This work is divided in two papers (Part I and Part II). In Part I, we study a class of polymodal logics (herein called the class of "Rare-logics") for which the set of terms indexing the modal operators are hierarchized in two levels: the set of Boolean terms and the set of terms built upon the set of Boolean terms. By investigating different algebraic properties satisfied by the models of the Rare-logics, reductions for decidability are established by faithfully translating the Rare-logics into more standard modal logics. The main idea of the translation consists in eliminating the Boolean terms by taking advantage of the components construction and in using various properties of the classes of semilattices involved in the semantics. The novelty of our approach allows us to prove new decidability results (presented in Part II), in particular for information logics derived from rough set theory and we open new perspectives to define proof systems for such logics (presented also in Part II).     

Family Processes and Treatment Outcome in the MTA: Negative/Ineffective Parenting Practices in Relation to Multimodal Treatment

To elucidate processes underlying therapeutic change in a large-scale randomized clinical trial, we examined whether alterations in self-reported parenting practices were associated with the effects of behavioral, medication, or combination treatments on teacher-reported outcomes (disruptive behavior, social skills, internalizing symptoms) in children with attention-deficit hyperactivity disorder (ADHD). Participants were 579 children with Combined-type ADHD, aged 7–9.9 years, in the Multimodal Treatment Study of Children with ADHD (MTA). We uncovered 2 second-order factors of parenting practices, entitled Positive Involvement and Negative/Ineffective Discipline. Although Positive Involvement was not associated with amelioration of the school-based outcome measures, reductions in Negative/Ineffective Discipline mediated improvement in children's social skills at school. For families showing the greatest reductions in Negative/Ineffective Discipline, effects of combined medication plus behavioral treatment were pronounced in relation to regular community care. Furthermore, only in combination treatment (and not in behavioral treatment alone) was decreased Negative/Ineffective Discipline associated with reduction in children's disruptive behavior at school. Here, children in families receiving combination treatment who showed the greatest reductions in Negative/Ineffective Discipline had teacher-reported disruptive behavior that was essentially normalized. Overall, the success of combination treatment for important school-related outcomes appears related to reductions in negative and ineffective parenting practices at home; we discuss problems in interpreting the temporal sequencing of such process-outcome linkages and the means by which multimodal treatment may be mediated by psychosocial processes related to parenting.