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Information obtained retrospectively from the abstraction of medical records is measurably less accurate than information obtained prospectively from research subjects. For certain items, more than half of the information is not available. This loss of information is related to the data types included in the study and by the assumptions that a researcher performing a retrospective study makes about implied versus explicitly stated responses. A model of information flow that incorporates the concepts of reliability and validity can be used to measure some of the loss of information that occurs at each step along the way from subject to clinician to medical record abstractor.

Using a comprehensive chemical genetics approach, we identified a member of the lignan natural product family, HTP-013, which exhibited significant cytotoxicity across various cancer cell lines. Correlation of compound activity across a panel of reporter gene assays suggested the vacuolar-type ATPase (v-ATPase) as a potential target for this compound. Additional cellular studies and a yeast haploinsufficiency screen strongly supported this finding. Competitive photoaffinity labeling experiments demonstrated that the ATP6V0A2 subunit of the v-ATPase complex binds directly to HTP-013, and further mutagenesis library screening identified resistance-conferring mutations in ATP6V0A2. The positions of these mutations suggest the molecule binds a novel pocket within the domain of the v-ATPase complex responsible for proton translocation. While other mechanisms of v-ATPase regulation have been described, such as dissociation of the complex or inhibition by natural products including bafilomycin A1 and concanamycin, this work provides detailed insight into a distinct binding pocket within the v-ATPase complex.

Of subjects discharged from the emergency department after visits for non-traumatic abdominal or flank pain, most improve within several days. Fewer than half follow-up with a family practitioner or a primary care provider. Emergency department revisits are uncommon and often for unrelated problems.

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