Research curricula in critical care fellowships--a survey

OBJECTIVES: To determine curriculum requirements and educational methods used by Critical Care fellowship training programs in fulfilling Residency Review Committee requirements for a research experience during Critical Care subspecialty training. DATA SOURCE: Responses from 163 (67%) of the 245 directors of accredited Anesthesiology, Medicine, Pediatric, and Surgical Critical Care fellowship training programs listed in the American Medical Association Graduate Medical Education Directory. DATA EXTRACTION: Survey information accepted as valid for each program was tabulated to answer study questions. DATA SYNTHESIS: Most (89%) Critical Care programs with 2- or 3-yr curricula meet Residency Review Committee requirements and provide nonclinical time for research. Only 63% of 1-yr curricula from Anesthesiology and Medicine provide a required research experience. Formal instruction in research topics is provided by lecture, journal club, or research conference in approximately 90% of fellowships. Academic productivity from fellowship programs is high, but not correlated with a program's requirement for research. CONCLUSION: Compliance with current Residency Review Committee requirements for active participation in research is poor for 1-yr fellowship curricula. Reasons for this failure are discussed and a modified requirement is proposed.     

Ag/AgCl/Cl- coated silver-stripe reference electrode

Severe airway obstruction caused by tonsillar enlargement can result in disturbances in body growth. In this study, 1136 children between 7 and 12 years of age, were evaluated and the size of their tonsils was investigated with regard to height and weight. This study was performed in the course of school screening, and correlation between estimated tonsil size and height and weight of the children was sought. Statistically, no such correlation was found (P > 0.05).     

Activation of the kexin from Schizosaccharomyces pombe requires internal cleavage of its initially cleaved prosequence

Members of the kexin family of processing enzymes are responsible for the cleavage of many proproteins during their transport through the secretory pathway. The enzymes themselves are made as inactive precursors, and we investigated the activation process by studying the maturation of Krp1, a kexin from the fission yeast Schizosaccharomyces pombe. Using a cell-free translation-translocation system prepared from Xenopus eggs, we found that Krp1 is made as a preproprotein that loses the presequence during translocation into the endoplasmic reticulum. The prosequence is also rapidly cleaved in a reaction that is autocatalytic and probably intramolecular and is inhibited by disruption of the P domain. Prosequence cleavage normally occurs at Arg-Tyr-Lys-Arg102/ (primary cleavage site) but can occur at Lys-Arg82 (internal cleavage site) and/or Trp-Arg99 when the basic residues are removed from the primary site. Cleavage of the prosequence is necessary but not sufficient for activation, and Krp1 is initially unable to process substrates presented in trans. Full activation is achieved after further incubation in the extract and is coincident with the addition of O-linked sugars. O glycosylation is not, however, essential for activity, and the crucial event appears to be cleavage of the initially cleaved prosequence at the internal site. Our results are consistent with a model in which the cleaved prosequence remains noncovalently associated with the catalytic domain and acts as an autoinhibitor of the enzyme. Inhibition is then relieved by a second (internal) cleavage of the inhibitory prosequence. Further support for this model is provided by our finding that overexpression of a Krp1 prosequence lacking a cleavable internal site dramatically reduced the growth rate of otherwise wild-type S. pombe cells, an effect that was not seen after overexpression of the normal, internally cleavable, prosequence or prosequences that lack the Lys-Arg102 residues.     

Automatic learning

Knowledge-based systems have made their mark in improving many manufacturing processes, but there is still a stumbling block in the process of converting human knowledge into a form where a computer or expert system can use it. The authors describe a successful way of deriving knowledge directly from raw data. The data gathered are processed for all shifts over a period of seven days to produce, for each shift, a value for the productivity variables.     

On the prebiotic synthesis of ribonucleotides: photoanomerisation of cytosine nucleosides and nucleotides revisited

Recent work has emphasised the importance of D-ribose aminooxazoline 1 in the synthesis of cytidine ribonucleosides under potentially prebiotic conditions. Upon treatment with cyanoacetylene, 1 is transformed into alpha-D-cytidine (alpha-2), and if an efficient means of anomerising this nucleoside or a derivative thereof were to be found, then the synthesis of one of the key beta-D-nucleosides required to make RNA would be realised. Photoanomerisation of alpha-2 has previously been described, but the yield was extremely low. Therefore, the present study was initiated to determine whether this low yield was the result of a low conversion or competing reaction pathways.