Incorporating ideas from computer-supported cooperative work

Many information systems have failed when deployed into complex health-care settings. We believe that one cause of these failures is the difficulty in systematically accounting for the collaborative and exception-filled nature of medical work. In this methodological review paper, we highlight research from the field of computer-supported cooperative work (CSCW) that could help biomedical informaticists recognize and design around the kinds of challenges that lead to unanticipated breakdowns and eventual abandonment of their systems. The field of CSCW studies how people collaborate with each other and the role that technology plays in this collaboration for a wide variety of organizational settings. Thus, biomedical informaticists could benefit from the lessons learned by CSCW researchers. In this paper, we provide a focused review of CSCW methods and ideas-we review aspects of the field that could be applied to improve the design and deployment of medical information systems. To make our discussion concrete, we use electronic medical record systems as an example medical information system, and present three specific principles from CSCW: accounting for incentive structures, understanding workflow, and incorporating awareness.     

The development of defensive behavior against predation by army ants

The development of defensive reaction in the ant Novomessor albisetosus against predation by army ants is studied in the laboratory and field. Two clusters of behavior emerge: escape with or without the brood, and aggressive defense. Escape develops specifically as a reaction against army ants and not in the presence of other ant species. Other behaviors develop with varying degrees of specificity toward army ants. All behaviors develop with age in workers isolated from experience with army ants. However, evidence is presented suggesting that experience with army ants alters the course of this development.     

Oxygen exchange and vascular resistance in the totally perfused rainbow trout

A whole trout preparation (Salmo gairdneri) externally ventilated with water and internally perfused with artificial medium via a cardiac pump is discribed for the study of O2 exchange and vascular resistance. As cardiac output (Q) was raised, ventral and dorsal aortic pressures increased while branchial (Rg) and systemic (Rs) vascular resistances fell, reflecting considerable passive distensibility. Arterial oxygenation was negative at low Qs due to significant internal O2 demand by the gill tissue, but increased to zero or positive values at intermediate Qs, and eventually declined at high Qs because of transit time limitation. O2 uptake from the ventilatory flow rose with increasing Q. Epinephrine (10(-5) M) decreased Rg, increased Rs, and enhanced arterial oxygenation. Artificial elevation of dorsal aortic pressure decreased Rg but did not affect arterial oxygenation. A 10-fold elevation of ventilatory flow increased arterial oxygenation but did not alter Rg or Rs. Endogenous metabolism of branchial tissue accounted for 11.7% of resting O2 uptake in vivo, and comprised an internal component taking O2 from perfusion flow and an external component drawing O2 from ventilatory flow.     

Influence of pinealectomy and photoperiod on courtship and nest-building in male doves

Sham-operated male doves displayed greater nesting activity under long days (16L:8D) than under short days (8L:16D). This difference was abolished by pinealectomy—the activity of long-day pinealectomized birds dropped to a level comparable to that seen on short days. Removal of the pineal had no effect under the short photoperiod. These results are not due to changes in peripheral androgen production as castrated, testosterone-implanted males also exhibited higher levels of nest-building on long days if sham-operated, but not if they were pinealectomized. Neither treatment had a significant effect on courtship or copulatory behavior. It is suggested that the pineal mediates the stimulatory effect of long photoperiods on hormonally-induced nest-building in doves.     

Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpoint

Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1-F-box). It forms an adapter bridge between Cullin-1 and the substrate-determining component, the F-box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3-D structure of human Skp1 suggested that the mutants would be compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope-tagged, and co-immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1(ts) suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3Delta and skp1(ts), implicating a novel role for Skp1 in the checkpoint-signalling cascade.     

Calpain inhibitor I reduces the development of acute and chronic inflammation

There is limited evidence that inhibition of the activity of the protease calpain I reduces inflammation. Here we investigate the effects of calpain inhibitor I in animal models of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis). We report here for the first time that calpain inhibitor I (given at 5, 10, or 20 mg/kg i.p. in the pleurisy model or at 5 mg/kg i.p every 48 hours in the arthritis model) exerts potent anti-inflammatory effects (eg, inhibition of pleural exudate formation, mononuclear cell infiltration, delayed the development of the clinical signs and histological injury) in vivo. Furthermore, calpain inhibitor I reduced (1) the staining for nitrotyrosine and poly (ADP-ribose) polymerase (immunohistochemistry) and (2) the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in joints from collagen-treated rats. Thus, prevention of the activation of calpain I reduces the development of acute and chronic inflammation. Inhibition of calpain I activity may represent a novel therapeutic approach for the therapy of inflammation.     

Quinupristin-dalfopristin-resistant Enterococcus faecium on chicken and in human stool specimens

BACKGROUND: The combination of the streptogramins quinupristin and dalfopristin was approved in the United States in late 1999 for the treatment of vancomycin-resistant Enterococcus faecium infections. Since 1974, another streptogramin, virginiamycin, has been used at subtherapeutic concentrations to promote the growth of farm animals, including chickens. METHODS: To determine the frequency of quinupristin-dalfopristin-resistant E. faecium, we used selective medium to culture samples from chickens purchased in supermarkets in Georgia, Maryland, Minnesota, and Oregon and stool samples from outpatients. RESULTS: Between July 1998 and June 1999, samples from 407 chickens from 26 stores in four states were cultured, as were 334 stool samples from outpatients. Quinupristin-dalfopristin-resistant E. faecium was isolated from 237 chicken carcasses and 3 stool specimens. The resistant isolates from stool had low-level resistance (minimal inhibitory concentration [MIC], 4 microg per milliliter; resistance was defined as a MIC of at least 4 microg per milliliter). The resistant isolates from chickens in general had higher levels of resistance (MICs ranging from 4 to 32 microg per milliliter; MIC required to inhibit 50 percent of isolates, 8 microg per milliliter). CONCLUSIONS: Quinupristin-dalfopristin-resistant E. faecium contaminates a large proportion of chickens sold in U.S. supermarkets. However, the low prevalence and low level of resistance of these strains in human stool specimens suggest that the use of virginiamycin in animals has not yet had a substantial influence. Foodborne dissemination of resistance may increase, however, as the clinical use of quinupristin-dalfopristin increases.