Fortunately, almost all patients requiring respiratory support do have these tests performed routinely every day. It is therefore extremely unlikely that a significant ALI would occur without the need to perform the chest x-ray and the arterial blood gas as a part of clinical care. Additional limitations of our approach come from the observational design of this study. First,

Inhibitors,research,lifescience,medical because participants are not randomly assigned to the exposures under investigation, our study is particularly prone to indication bias, in that patients receiving certain therapies may be systematically different from those not receiving the therapies. If these differences are associated with the outcome of interest, the study results may be biased. Large sample size and a comprehensive collection of exposure variables will mitigate the potential bias by enabling our statisticians to adjust for any measured factor found to predict the use of each exposure under investigation. However, some important factors may be unknown or unmeasured, resulting Inhibitors,research,lifescience,medical in residual confounding and bias. The population based sample is clearly a strong point of our study. However, all patients will be treated in the two

hospitals of the single teaching medical center, and, although Inhibitors,research,lifescience,medical internal validity will be high, the study results may not generalize to patients in other settings. Moreover, we will not be able to take advantage of additional variability Inhibitors,research,lifescience,medical in practice such as would be possible in multicenter studies involving different parts of the world. Long study period raises another question about whether the exposures, prognosis, and incidence of ALI will be stable enough to allow the proposed investigation. Fast pace changes in health care delivery and quality improvement initiatives could Inhibitors,research,lifescience,medical plausibly lead to the change in frequency of some

of the proposed in-hospital exposures. Should changes in practice occur during the study period, our detailed observation of both practice and outcomes will give us an opportunity to correlate changes in practice with the development and outcome of ALI and possibly be able to make stronger causal inferences from the observed associations. This causal translational research study will not affect the outcome of studied patients (this is a non-intervention epidemiologic study) but will help in better understanding the clinical pathogenesis of ALI and the design of future ALI prevention strategies. Since the therapeutic options are limited once ALI develops, the prevention is (-)-p-Bromotetramisole Oxalate paramount. Unfortunately, effective prevention interventions do not currently exist, and our knowledge about clinical pathogenesis of ALI is limited. By identifying patients at high risk earlier (in the Abexinostat cell line emergency department and operating room), and collecting biospecimens and clinical data before ICU admission we hope to improve our understanding of ALI and identify targets for future quality improvement interventions and ALI prevention trials.