Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units

Objective. To determine the population incidence and outcome of severe sepsis occurring in adult patients treated in Australian and New Zealand intensive care units (ICUs), and compare with recent retrospective estimates from the USA and UK. Design. Inception cohort study. Setting. Twenty-three closed multi-disciplinary ICUs of 21 hospitals (16 tertiary and 5 university affiliated) in Australia and New Zealand. Patients. A total of 5878 consecutive ICU admission episodes. Measurements and results. Main outcome measures were population-based incidence of severe sepsis, mortality at ICU discharge, mortality at 28 days after onset of severe sepsis, and mortality at hospital discharge. A total of 691 patients, 11.8 (95% confidence intervals 10.9-12.6) per 100 ICU admissions, were diagnosed with 752 episodes of severe sepsis. Site of infection was pulmonary in 50.3% of episodes and abdominal in 19.3% of episodes. The calculated incidence of severe sepsis in adults treated in Australian and New Zealand ICUs is 0.77 (0.76-0.79) per 1000 of population. 26.5% of patients with severe sepsis died in ICU, 32.4% died within 28 days of the diagnosis of severe sepsis and 37.5% died in hospital. Conclusion. In this prospective study, 11.8 patients per 100 ICU admissions were diagnosed with severe sepsis and the calculated annual incidence of severe sepsis in adult patients treated in Australian and New Zealand ICUs is 0.77 per 1000 of population. This figure for the population incidence falls in the lower range of recent estimates from retrospective studies in the U.S. and the U.K.

Responsibility to protect or Trojan Horse? The crisis in darfur and humanitarian intervention after Iraq

What does the world's engagement with the unfolding crisis in Darfur tell us about the impact of the Iraq war on the norm of humanitarian intervention? Is a global consensus about a "responsibility to protect" more or less likely? There are at least three potential answers to these questions. Some argue that the merging of strategic interests and humanitarian goods amplified by the intervention in Afghanistan makes it more likely that the world's most powerful states will act to prevent or halt humanitarian crises. Others insist that the widespread perception that the United States and its allies "abused" humanitarian justifications to legitimate its invasion of Iraq has set back efforts to build a global consensus about humanitarian action. A third group argues that the "responsibility to protect" inhibits the potential for abuse and, as a result, consensus is likely to strengthen post-Iraq for precisely this reason. Through a detailed study of the international engagement with Darfur, I suggest that the latter two arguments have merit but need to be adjusted. I argue that the humanitarian intervention norm has changed in two subtle ways. First, while the strength of the norm itself has not changed, the credibility of the United States and U.K. as "norm carriers" has been significantly undermined. Second, while the "responsibility to protect" has been invoked to support international activism, it has also re-legitimated anti-interventionist arguments.

Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26

Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite 150 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families ( 931 from an Australian group and 245 from a U. K. group), each with at least two members-mainly affected sister pairs-with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 ( maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 MLS p 2.09). Minor peaks with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.

Diabetes as a tracer condition in international benchmarking of health systems

OBJECTIVE - To assess the performance of health systems using diabetes as a tracer condition. RESEARCH DESIGN AND METHODS - We generated a measure of case-fatality among young people with diabetes Using the mortalily-to-incidence ratio (M/I ratio) for 29 industrialized countries using published data on diabetes incidence and mortality. Standardized incidence rates for ages 0-14 years were extracted from the World Health Organization DiaMond Study for the period 1990-1994; data on death from diabetes for ages 0-39 years were obtained from the World Health Organization Mortality database and converted into age-standardized death rates for the period 1994-1998, using the European standard population. RESULTS - The MA ratio varied > 10-fold. These relative differences appear similar to those observed in cohort studies of mortality among young people with type I diabetes in five countries. A sensitivity analysis showed that using plausible assumptions about potential overestimation of diabetes as a cause of death and underestimation of incidence rates in the U.S. yields an M/I ratio that would still be twice as high as in the U.K. or Canada. CONCLUSIONS - The M/I ratio for diabetes provides a means of differentiating countries on quality of care for people with diabetes. It is solely an indicator of potential problems, a basis for Stimulating more detailed assessments of whether such problems exist, and what can be done to address them.

Verifying data refinements using a model checker

In this paper, we consider how refinements between state-based specifications (e.g., written in Z) can be checked by use of a model checker. Specifically, we are interested in the verification of downward and upward simulations which are the standard approach to verifying refinements in state-based notations. We show how downward and upward simulations can be checked using existing temporal logic model checkers. In particular, we show how the branching time temporal logic CTL can be used to encode the standard simulation conditions. We do this for both a blocking, or guarded, interpretation of operations (often used when specifying reactive systems) as well as the more common non-blocking interpretation of operations used in many state-based specification languages (for modelling sequential systems). The approach is general enough to use with any state-based specification language, and we illustrate how refinements between Z specifications can be checked using the SAL CTL model checker using a small example.

Vitamin D action and regulation of bone remodeling: Suppression of osteoclastogenesis by the mature osteoblast

Vitamin D acts through the immature osteoblast to stimulate osteoclastogenesis. Transgenic elevation of VDR in mature osteoblasts was found to inhibit osteoclastogenesis associated with an altered OPG response. This inhibition was confined to cancellous bone. This study indicates that vitamin D-mediated osteoclastogenesis is regulated locally by OPG production in the mature osteoblast.