Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.

Prevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.

Background-In the past 10 years, medication errors have come to be recognised as an important cause of iatrogenic disease in hospital patients. Aims-To determine the incidence and type of medication errors in a large UK paediatric hospital over a five year period, and to ascertain whether any error prevention programmes had influenced error occurrence. Methods-Retrospective review of medication errors documented in standard reporting forms completed prospectively from April 1994 to August 1999. Main outcome measure was incidence of error reporting, including pre-and postinterventions. Results-Medication errors occurred in 0.15% of admissions (195 errors; one per 662 admissions). While the highest rate occurred in neonatal intensive care (0.98%), most errors occurred in medical wards. Nurses were responsible for most reported errors (59%). Errors involving the intravenous route were commonest (56%), with antibiotics being the most frequent drug involved (44%). Fifteen (8%) involved a tenfold medication error. Although 18 (9.2%) required active patient intervention, 96% of errors were classified as minor at the time of reporting. Forty eight per cent of parents were not told an error had occurred. The introduction of a policy of double checking all drugs dispensed by pharmacy staV led to a reduction in errors from 9.8 to 6 per year. Changing the error reporting form to make it less punitive increased the error reporting rate from 32.7 to 38 per year. Conclusion-The overall medication error rate was low. Despite this there are clear opportunities to make system changes to reduce error rates further. (Arch Dis Child 2000;83:492-497)

Normal aging is associated with impairments in stimulus recognition. In the current investigation, object recognition was tested in adult and aged rats with the standard spontaneous object recognition (SOR) task or two variants of this task. On the standard SOR task, adult rats showed an exploratory preference for the novel object over delays up to 24 hours, whereas the aged rats only showed significant novelty discrimination at the 2 min delay. This age difference appeared to be due to the old rats behaving as if the novel object was familiar. To test this hypothesis directly, rats participated in a variant of the SOR task that allowed the exploration times between the object familiarization and the test phases to be compared, and this experiment confirmed that aged rats falsely “recognize” the novel object. A final control examined whether or not aged rats exhibited reduced motivation to explore objects. In this experiment, when the environmental context changed between familiarization and test, young and old rats failed to show an exploratory preference because both age groups spent more time exploring the familiar object. Together these findings support the view that age-related impairments in object recognition arise from old animals behaving as if novel objects are familiar, which is reminiscent of behavioral impairments in young rats with perirhinal cortical lesions. The current experiments thus suggest that alterations in the perirhinal cortex may be responsible for reducing aged animals’ ability to distinguish new stimuli from ones that have been encountered previously.