Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice.

There is strong evidence that growth-associated protein (GAP-43), a protein found only in the nervous system, regulates the response of neurons to axonal guidance signals. However, its role in complex spatial patterning in cerebral cortex has not been explored. We show that mice lacking GAP-43 expression (-/-) fail to establish the ordered whisker representation (barrel array) normally found in layer IV of rodent primary somatosensory cortex. Thalamocortical afferents to -/- cortex form irregular patches in layer IV within a poorly defined cortical field, which varies between hemispheres, rather than the stereotypic, whisker-specific, segregated map seen in normal animals. Furthermore, many thalamocortical afferents project abnormally to widely separated cortical targets. Taken together, our findings indicate a loss of identifiable whisker territories in the GAP-43 -/- mouse cortex. Here, we present a disrupted somatotopic map phenotype in cortex, in clear contrast to the blurring of boundaries within an ordered whisker map in other barrelless mutants. Our results indicate that GAP-43 expression is critical for the normal establishment of ordered topography in barrel cortex.

Changes to manuscripts during the editorial process: characterizing the evolution of a clinical paper.

CONTEXT: Biomedical manuscripts undergo substantive change as a result of the peer review and editorial revision processes. OBJECTIVE: To characterize quantitatively problems in manuscripts identified during peer review and changes made to address these problems. DESIGN AND SETTING: Descriptive analysis of manuscripts submitted to and articles published by the Annals of Internal Medicine. A taxonomy of problems that occur in reporting clinical research was developed from analysis of changes made to 7 manuscripts between submission and publication (published October 15, 1996, and November 1, 1996). The taxonomy was used to characterize changes to 12 additional manuscripts (published January 15, 1997, to April 1, 1997). MAIN OUTCOME MEASURE: Types of problems necessitating changes to manuscripts during peer review and revision. RESULTS: Changes occurred because of 5 types of problems: too much information, too little information, inaccurate information, misplaced information, and structural problems. Changes most often occurred because information was missing or extraneous. The distribution of changes seemed to be influenced by the type of information involved (such as background or conclusions). CONCLUSION: The proposed framework may be useful for characterizing quantitatively the effects of peer review and for comparing those effects across editors, journals, and specialties.

The Expert Consensus Guidelines for treating depression in bipolar disorder.

We present expert consensus guideline recommendations for the treatment of bipolar depression. These were arrived at through the statistical aggregation of the survey responses of 61 leading clinical researchers to eight questions about the key decision points in the management of bipolar depression. The experts' first-line recommendation for treating psychotic depression in bipolar disorder is to provide a combination of mood stabilizer, antidepressant, and neuroleptic medication. For severe, but nonpsychotic bipolar depression, the experts recommend the combination of a mood stabilizer and an antidepressant. For milder bipolar depression, a mood stabilizer and an antidepressant together or a mood stabilizer alone would be first line. The experts' antidepressant dose and dosing schedule recommendations are equivalent for unipolar and bipolar depression, but the experts recommend a faster discontinuation of antidepressants during the maintenance phase in bipolar patients--probably to reduce the risk of rapid cycling. Among the antidepressants, the experts prefer bupropion and the serotonin reuptake inhibitors as first line. They also believe that bupropion is least likely among antidepressants to cause switches to mania. Among mood stabilizers, the experts rate lithium as most likely to have a direct antidepressant effect.