Publications

STUDY OBJECTIVE

Emergency department (ED) closures threaten community access to emergency services, but few data exist to describe factors associated with closure. We evaluate factors associated with ED closure in California and seek to determine whether hospitals serving more vulnerable populations have a higher rate of ED closure.

METHODS

This was a retrospective cohort study of California hospital EDs between 1998 and 2008, using hospital- and patient-level data from the California Office of Statewide Health Planning and Development (OSHPD), as well as OSHPD patient discharge data. We examined the effects of hospital and patient factors on the hospital's likelihood of ED closure by using Cox proportional hazards models.

RESULTS

In 4,411 hospital-years of observation, 29 of 401 (7.2%) EDs closed. In a model adjusted for total ED visits, hospital discharges, trauma center and teaching status, ownership, operating margin, and urbanicity, hospitals with more black patients (hazard ratio [HR] 1.41 per increase in proportion of blacks by 0.1; 95% confidence interval [CI] 1.16 to 1.72) and Medi-Cal recipients (HR 1.17 per increase in proportion insured by Medi-Cal by 0.1; 95% CI 1.02 to 1.34) had higher risk of ED closure, as did for-profit institutions (HR 1.65; 95% CI 1.13 to 2.41).

CONCLUSION

The population served by EDs and hospitals' profit model are associated with ED closure. Whether our findings are a manifestation of poorer reimbursement in at-risk EDs is unclear.

Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further.

Food insecurity, which affects >1 billion people worldwide, is inextricably linked to the HIV epidemic. We present a conceptual framework of the multiple pathways through which food insecurity and HIV/AIDS may be linked at the community, household, and individual levels. Whereas the mechanisms through which HIV/AIDS can cause food insecurity have been fairly well elucidated, the ways in which food insecurity can lead to HIV are less well understood. We argue that there are nutritional, mental health, and behavioral pathways through which food insecurity leads to HIV acquisition and disease progression. Specifically, food insecurity can lead to macronutrient and micronutrient deficiencies, which can affect both vertical and horizontal transmission of HIV, and can also contribute to immunologic decline and increased morbidity and mortality among those already infected. Food insecurity can have mental health consequences, such as depression and increased drug abuse, which, in turn, contribute to HIV transmission risk and incomplete HIV viral load suppression, increased probability of AIDS-defining illness, and AIDS-related mortality among HIV-infected individuals. As a result of the inability to procure food in socially or personally acceptable ways, food insecurity also contributes to risky sexual practices and enhanced HIV transmission, as well as to antiretroviral therapy nonadherence, treatment interruptions, and missed clinic visits, which are strong determinants of worse HIV health outcomes. More research on the relative importance of each of these pathways is warranted because effective interventions to reduce food insecurity and HIV depend on a rigorous understanding of these multifaceted relationships.

Semen is the major vector for HIV-1 transmission. We previously isolated C-proximal fragments of the prostatic acid phosphatase (PAP) from semen which formed amyloid fibrils that potently enhanced HIV infection. Here, we used the same methodology and identified another amyloidogenic peptide. Surprisingly, this peptide is derived from an N-proximal fragment of PAP (PAP85-120) and forms, similar to the C-proximal fragments, positively charged fibrillar structures that increase virion attachment to cells. Our results provide a first example for amyloid formation by fragments of distinct regions of the same precursor and further emphasize the possible importance of amyloidogenic peptides in HIV transmission.

Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh)/Kit(W-sh) mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh)/Kit(W-sh) mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.