In 1981-1982, a Massachusetts Hospital Association and Massachusetts Blue Cross-Blue Shield task force reviewing ancillary services found that the use of respiratory therapy at New England Deaconess Hospital far exceeded the statewide average. These findings led to a hospital-wide effort to reduce ancillary services. As part of this effort, we studied the effect of the reductions in respiratory therapy on patient outcome. At the beginning of the study, senior respiratory therapists advised physicians about the optimal use of various respiratory-therapy services, including their discontinuation when no longer necessary. One year after the intervention began, we analyzed the use of respiratory therapy by employing data-collection techniques that were identical to those used by the task force. Marked reductions in all categories of respiratory therapy had occurred, but morbidity and mortality from pulmonary disorders had not increased. In the largest group studied--patients undergoing coronary-artery bypass surgery--the charges for respiratory therapy, the length of hospital stay, and pulmonary complications had all decreased. We conclude that consistent application of prescribed guidelines for respiratory therapy results in marked decreases in its use and that such decreases can be achieved without a reduction in the quality of care.
The XPF-ERCC1 complex, a highly conserved structure-specific endonuclease, functions in multiple DNA repair pathways that are pivotal for maintaining genome stability, including nucleotide excision repair, interstrand crosslink repair, and homologous recombination. XPF-ERCC1 incises double-stranded DNA at double-strand/single-strand junctions, making it an ideal enzyme for processing DNA structures that contain partially unwound strands. Here, we have examined the role of the XPF-ERCC1 complex in the model bryophyte
Physcomitrella patens
which exhibits uniquely high gene targeting frequencies. We undertook targeted knockout of the
Physcomitrella ERCC1
and
XPF
genes. Mutant analysis shows that the endonuclease complex is essential for resistance to UV-B and to the alkylating agent MMS, and contributes to the maintenance of genome integrity but is also involved in gene targeting in this model plant. Using different constructs we determine whether the function of the XPF-ERCC1 endonuclease complex in gene targeting was removal of 3′ non-homologous termini, similar to SSA, or processing of looped-out heteroduplex intermediates. Interestingly, our data suggest a role of the endonuclease in both pathways and have implications for the mechanism of targeted gene replacement in plants and its specificities compared to yeast and mammalian cells.
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