Objective To determine the association between poor sleep quality, fatigue, and self-reported safety outcomes among Emergency Medical Services (EMS) workers. Methods We used convenience sampling of EMS agencies and a cross-sectional survey design. We administered the 19-item Pittsburgh Sleep Quality Index (PSQI), 11-item Chalder Fatigue Questionnaire (CFQ), and 44-item EMS Safety Inventory (EMS-SI) to measure sleep quality, fatigue, and safety outcomes, respectively. We used a consensus process to develop the EMS-SI, which was designed to capture three composite measurements of EMS worker injury, medical errors and adverse events (AE), and safety compromising behaviors. We used hierarchical logistic regression to test the association between poor sleep quality, fatigue, and three composite measures of EMS worker safety outcomes. Results We received 547 surveys from 30 EMS agencies (a 35.6% mean agency response rate). The mean PSQI score exceeded the benchmark for poor sleep (6.9, 95%CI 6.6, 7.2). Greater than half of respondents were classified as fatigued (55%, 95%CI 50.7, 59.3). Eighteen percent of respondents reported an injury (17.8%, 95%CI 13.5, 22.1), forty-one percent a medical error or AE (41.1%, 95%CI 36.8, 45.4), and 89% (95%CI 87, 92) safety compromising behaviors. After controlling for confounding, we identified 1.9 greater odds of injury (95%CI 1.1, 3.3), 2.2 greater odds of medical error or AE (95%CI 1.4, 3.3), and 3.6 greater odds of safety compromising behavior (95%CI 1.5, 8.3) among fatigued respondents versus non-fatigued respondents. Conclusions In this sample of EMS workers, poor sleep quality and fatigue is common. We provide preliminary evidence of an association between sleep quality, fatigue, and safety outcomes.

The product of the CDC7 gene of Saccharomyces cerevisiae appears to have multiple roles in cellular physiology. It is required for the initiation of mitotic DNA synthesis. While it is not required for the initiation of meiotic DNA replication, it is necessary for genetic recombination during meiosis and for the formation of ascospores. It has also been implicated in an error-prone DNA repair pathway. Plasmids Use of the budding yeast Saccharomyces cerevisiae as a model for studies on the eucaryotic cell cycle relies heavily on temperature-sensitive mutations in cell division cycle (CDC) genes (32, 35). Characterization of these mutants has led to the formulation of a model in which progression through the cell cycle is determined by a set of interrelated pathways, each organized as a dependent sequence of events requiring the action of specific gene products. One such pathway, operating late in the Gi phase of the cell cycle, requires the function of the CDC7 gene product (12). Cells carrying a thermosensitive lesion in the CDC7 gene arrest at the restrictive temperature as budded cells with separated spindle-pole bodies but without an elongated spindle apparatus and without initiating DNA synthesis (5, 12). Upon return to permissive conditions cdc7 cells are able to enter the S phase and subsequently complete a round of DNA synthesis without further protein synthesis (14).In contrast to the requirement for CDC7 function to initiate mitotic DNA synthesis, premeiotic DNA replication occurs normally in cdc7 homozygous diploids under the restrictive condition (43). However, these diploids fail to form a synaptonemal complex, to show commitment to genetic recombination, or to form ascospores (40). Thus, although cdc7 strains are defective in both mitotic and meiotic cell cycles, the lesion appears to affect each pathway in a quite distinct manner. In addition to having roles in the mitotic and meiotic pathways, the CDC7 gene product has been implicated in DNA repair as a member of the RAD6 epistasis group, since strains carrying a cdc7 mutation show almost no mutagenic repair in response to a variety of damaging agents (31).To elucidate the role of the CDC7 gene product in the various cellular functions in which it is implicated and to determine whether differential expression of the CDC7 gene is involved with its cell cycle functions, we and others (24) have begun a molecular analysis of the CDC7 gene. In this paper we describe the cloning of the CDC7 gene, the characterization of its transcriptional product, the nucleotide sequence of the gene, and the regions of homology between the predicted protein products of the CDC7 and CDC28 genes. MATERIALS AND METHODSStrains and media. Escherichia coli HB101 (F-thi leu pro hsdR hsdM recA end!) and HW87 [F-A(araD139-leu) lacX74 galK hsdR rpsL srb recA] were used as hosts for the routine maintenance and propagation of plasmids. Bacterial cultures were grown in L broth or supplemented M9 medium (26); when necessary, ampicillin was added to media to a final concentration of...

Background-Fatigue is common among medical professionals and has been linked to poor performance and medical error.

Although human immunodeficiency virus (HIV)-infected subjects without AIDS have a high frequency of HIV-specific CD8 T lymphocytes, cellular immunity is unable to control infection. Freshly isolated lymphocytes often do not lyse HIV-infected targets in 4-

The functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN-γ after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN-γ–producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN-γ–producing cells could be detected only after IL-2 was added. IFN-γ–producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex–peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2–expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN-γ was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2.

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Introduction-Workplace attitude, beliefs and culture may impact the safety of patient care. This study characterized perceptions of safety culture in a nationwide sample of Emergency Medical Services (EMS) agencies.

The product of the CDC7 gene of Saccharomyces cerevisiae is known to be required in the mitotic cell cycle for the initiation of DNA replication. We show that changes in transcript levels do not account for this stage-specific function, since the steady-state mRNA concentration remains constant at 1 copy per cell throughout the cell cycle. By measuring the cell division capacity of a cdc7::URA3 mutant after loss of a single-copy plasmid containing the CDC7 gene, we show that the CDC7 protein is present in at least 200-fold excess of the amount required for a single cell division. These results appear to exclude periodic transcription or translation as a means by which CDC7 function is regulated. In contrast, the CDC7 protein is known to be dispensible for meiotic S phase, but is required for synaptonemal complex formation and recombination. We found that the CDC7 transcript level does vary during meiosis, reaching a maximum near the time at which recombination occurs. Meiotic spores containing a cdc7 null allele germinate but fail to complete cell division. Apparently the excess CDC7 product present in mitotic cells is physically excluded from the spores (or becomes inactivated) and must be produced de novo after germination. The cdc7-1 allele had previously been shown to confer a reduction in the rate of induced mutation. We show that the cloned wild-type CDC7 gene not only complements this defect, but that when the CDC7 gene is on a multiple copy plasmid, induced mutagenesis is increased. Therefore, in contrast to the excess CDC7 activity for cell division, the level of activity for some error-prone repair process may be normally limiting.Cell division cycle (cdc) mutants of yeast are thought to have defects in proteins which perform functions at specific points in the mitotic cell cycle (18). These mutants often have defects in meiosis as well (27). Temperature-shift experiments with temperature-sensitive mutants of CDC7 have shown that the CDC7 gene product is required for initiation of the mitotic S phase (3). In contrast, meiotic DNA replication appears to be initiated and completed at the restrictive temperature. However, synaptonemal complex formation and recombination are defective (22,27). The CDC7 gene product is also implicated in DNA repair, since a cdc7-J mutant displays a reduction in induced mutagenesis with DNA-damaging agents (15). Because all cdc7 mutants are recessive (4), these cdc7 mutant phenotypes most likely result from a deficiency of CDC7 protein activity in the cell.We have previously shown that the CDC7 gene produces a 1.7-kilobase (kb) poly(A)+ mRNA and encodes a 56-to 58.2-kilodalton protein with homology to protein kinases (16). These findings lend credence to the hypothesis that the CDC7 protein acts by phosphorylating specific proteins involved with the cell cycle (16). Since the cell cycle stage-specific function of the CDC7 gene might be regulated by periodic changes in the level of its transcripts, we have examined this possibility, as well as the possibility of transcript le...