Annals of the New York Academy of Sciences
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Economic choice is the behavior observed when individuals select one of many available options solely based on subjective preferences. Behavioral evidence suggests that economic choice entails two mental processes: values are first assigned to the available options, and a decision is subsequently made between these values. Numerous reports show that lesions to the orbitofrontal cortex (OFC) lead to choice deficits in various domains, and imaging studies indicate that the OFC activates when people make choices. ⋯ Most importantly, neurons in the OFC encode economic value per se, not as a modulation of sensory or motor processes. This trait distinguishes the value representation in the OFC from that observed in other brain areas. That OFC neurons encode economic value independently of visuomotor contingencies suggests that economic choice is fundamentally a choice between goods (good-based model) rather than a choice between actions (action-based model).
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Our goal globally is to better identify individuals at risk for osteoporotic fracture so that those at high risk can be treated and unnecessary treatment for those at low risk can be avoided. Bone mineral density (BMD) information is not sufficient to identify all patients at high risk. Approximately half of patients in the community with fractures do not have osteoporosis by the 1994 World Health Organization BMD criteria. ⋯ The use of clinical risk factors with or without BMD information will improve gradient of risk and help us better identify patients at high risk for fracture. The clinical risk factors identified can be integrated to predict a 10-year absolute risk or probability of fracture. Intervention thresholds based on absolute risk will be defined regionally based on each nation's ability and willingness to pay.
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Ann. N. Y. Acad. Sci. · Oct 2007
ReviewDrugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress.
The molecular chaperone HSP90 has emerged as an exciting target for cancer treatment. We review the potential advantages of HSP90 inhibitors, particularly the simultaneous combinatorial depletion of multiple oncogenic "client" proteins, leading to blockade of many cancer-causing pathways and the antagonism of all of the hallmark pathological traits of malignancy. Cancer selectivity is achieved by exploiting cancer "dependencies," including oncogene addiction and the stressed state of malignant cells. ⋯ Potential new approaches are discussed, for example, interference with cochaperone binding and function in the superchaperone complex. Biomarkers for use with HSP90 inhibitors are described. We stress how basic and translational research has been mutually beneficial and indicate future directions to enhance our understanding of molecular chaperones and their exploitation in cancer and other diseases.
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Ann. N. Y. Acad. Sci. · Oct 2007
ReviewEvidence-based practice: limitations and successful implementation.
Evidence-based practice (EBP) has been heralded as the most appropriate way of ensuring that patients receive the most effective care possible. It does, however, have several limitations. It is also not enough just to locate and evaluate the evidence without implementing it. This paper discusses EBP and its limitations and potential barriers; it also suggests strategies for changing current practices to more evidence-based ones according to an accurate understanding of the concept of EBP.
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Ann. N. Y. Acad. Sci. · Sep 2007
Interstitial lung disease associated with systemic sclerosis: what is the evidence for efficacy of cyclophosphamide?
Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) that may be responsible for severe restrictive lung disease and represents one of the two main causes of disease-related death in SSc patients. Since 1993, the beneficial effect of oral or intravenous cyclophosphamide (CYC) in the treatment of SSc-related ILD has been reported in retrospective studies, one study showing improvement of pulmonary function test scores and/or chest computed tomography at 1 year and improvement of survival at 16 months. The results of two controlled trials were recently reported. ⋯ This trial did not demonstrate significant improvement of the primary or secondary endpoints in the active treatment group versus placebo. Since with the exception of the study of Silver et al. none of the patients included in retrospective or prospective studies were selected on the basis of progression of ILD. Since only a minority of SSc patients develops severe ILD, we propose that further studies evaluating CYC should focus on the subgroup of SSc patients with worsening ILD.