Task interference as a neuronal basis for the cost of cognitive flexibility.

Humans and animals have an impressive ability to juggle multiple tasks in a constantly changing environment. This flexibility, however, leads to decreased performance under uncertain task conditions. Here, we combined monkey electrophysiology, human psychophysics, and artificial neural network modeling to investigate the neuronal mechanisms of this performance cost. We developed a behavioural paradigm to measure and influence participants' decision-making and perception in two distinct perceptual tasks. Our data revealed that both humans and monkeys, unlike an artificial neural network trained for the same tasks, make less accurate perceptual decisions when the task is uncertain. We generated a mechanistic hypothesis by comparing this neural network trained to produce correct choices with another network trained to replicate the participants' choices. We hypothesized, and confirmed with further behavioural, physiological, and causal experiments, that the cost of task flexibility comes from what we term task interference. Under uncertain conditions, interference between different tasks causes errors because it results in a stronger representation of irrelevant task features and entangled neuronal representations of different features. Our results suggest a tantalizing, general hypothesis: that cognitive capacity limitations, both in health and disease, stem from interference between neural representations of different stimuli, tasks, or memories.

Meeting patients' needs with patient information systems: potential benefits of qualitative research methods.

This article reports on our pilot evaluation of an electronic patient information system for children with amblyopia and their parents. The aim was to investigate whether the information system would be able to improve the quality of care, as indicated by an improvement in the effectiveness and efficiency of care, and in an increase in patient satisfaction. In the pilot evaluation, we used qualitative research methods, exploring the impact of the information system on children and their parents, with the aim to find suitable indicators for a potential further, quantitative study. Yet we found that the system was little used and had marginal effects on the quality of care for children with amblyopia and their parents. It appeared that the main problem underlying this patient information system was that the needs of those people who actually would be using the system had never really been investigated. The designers had built their assumptions about these needs into the system. These appeared to be mistaken at so many levels that the system could not become a success. As a result of this pilot evaluation, the patient information project was thoroughly transformed. This study makes clear that a thorough exploration of user needs before building the system, using qualitative research methods, may be crucial because it can prevent mismatches and maximizes the chance that the eventual information system meets its most important aim: to enhance patient empowerment and improve the quality of care.

Solar ultraviolet radiation induces enhanced accumulation of oxygen radicals in murine SLE-derived splenocytes in vitro.

Although sunlight is known to induce generalized manifestation in systemic lupus erythematosus (SLE) patients, its underlying mechanism remains obscure. In the present study we have investigated whether UVA (320-400 nm), the most predominant UV component in solar radiation, induces enhanced accumulation of reactive oxygen species in murine SLE-derived cells (MRL/l) in comparison to normal cells (Balb/c), as measured by oxygen (O2) consumption, by means of a Clark-type electrode. Our data show enhanced O2 consumption by MRL/1 cells (which correlates with the formation of reactive oxygen species), accompanied by decreased viability, in comparison to irradiated normal cells. This finding suggests that increased accumulation of reactive oxygen species contributes to the enhanced photosensitivity observed in SLE patients.

Sequence analysis of cloned human satellite DNAs reveals nonrandom variations.

We have cloned, from the genome of HeLa cells, related 1.8-kb highly repetitive EcoRI satellite II (and III) DNA family members that displayed a high degree of TaqI and HinfI variations. Comparative sequence analysis of these cloned DNAs suggests that highly repetitive satellite DNAs may have evolved and diversified from the rapid amplification of a pentameric unit (5' TTCCA 3'), by processes including random and non-random mutations. Base conservation, as well as mutational hotspots, were found associated with these related satellite II and III DNAs. The accumulation of C to G transversions within the pentamers, generating TaqI and HinfI sites, as well as C to T transitions at CpN dinucleotides, appear to be responsible for much of the microheterogeneity observed between related satellite II and III DNA family members.

A cloned fragment of HeLa DNA containing consensus sequences of satellite II and III DNA hybridizes with the Drosophila P-element and with the 1.8 kb family of human KpnI fragments.

We have cloned a repetitive EcoRI fragment from the human genome which displays weak homologies with the Drosophila melanogaster transposable P-element. This cloned DNA appeared not to be a mobile element but, instead, a divergent member of human satellite II or III DNAs. We present here the first complete nucleotide sequence of a 1.797 kilobase pair (kb) satellite-like DNA. Moreover, this EcoRI satellite monomer contains a unique sequence of 49 basepairs (bp) that is devoid of the satellite consensus repeat 5'TTCCA3'. Southern hybridization analysis revealed that the cloned insert is closely related to a highly repetitive 1.8 kb KpnI family of tandemly organized satellite DNAs. Thus, the relationships among these satellite DNA families appear to be complex and may be a factor in their copy number, position and spatial organization.