The results of recent replication studies suggest that false positive findings are a big problem in empirical finance. We contribute to this debate by reviewing a sample of articles dealing with the short-term directional forecasting of the prices of stocks, commodities, and currencies. Screening all relevant articles published in 2016 by one of the 96 journals covered by the Social Sciences Citation Index in the category “Business, Finance,” we select only those studies that use easily accessible data of daily or higher frequency. We examine each study in detail, from the selection of the dataset to the interpretation of the results. We also include empirical analyses to illustrate the shortcomings of certain approaches. There are three main findings from our review. First, the number of selected papers is very low, which is surprising even when the strict selection criteria are taken into account. Second, there are hardly any relevant studies that use high-frequency data—despite the hype about financial big data and machine learning. Third, the economic significance of the findings—for example, their usefulness for trading purposes—is questionable. In general, apparently good forecasting performance does not translate into profitability once realistic transaction costs and the effect of data snooping are taken into account. Other typical problems include unsuitable benchmarks, short evaluation periods, and nonoperational trading strategies. 相似文献
Program evaluation can support capacity building and inform practice and policy. Yet long-term efforts to ensure evaluation use (EU) in the humanitarian sector are seldom documented, leaving much uncertainty about EU conditions. This study examined conditions that influenced EU by stakeholders of a humanitarian non-governmental organization (NGO) in Burkina Faso striving to base its health care program on solid evidence. It used 36 qualitative semi-structured interviews and a single case study design to document stakeholders’ (n?=?26) perception of EU conditions. Analyses focussed on characteristics of five broad conditions of research use previously documented. Results demonstrate that EU was facilitated by intended users with proactive attitudes, research experience, and willingness to participate in program evaluations. Also helpful was an organizational culture that valued learning, feedback, and accountability, wherein leaders collaborated toward common goals. Evaluation-based knowledge that met information needs and that was actionable, contextualized, and quickly accessible enhanced EU. Knowledge transfer strategies promoting EU were diverse, participatory, adapted to needs, and regularly followed up. Evaluators who were trusted, experienced, credible, and adaptable, promoted EU most effectively. Conversely, EU was compromised when intended users felt distrusting, uninformed, or unable to engage in program evaluations. Knowledge contradicting expectations or deemed inapplicable impeded EU. Adapting knowledge transfer strategies required time and interactions. Initially, evaluations were not sufficiently adapted and put into plain language, which hampered EU. EU conditions are numerous and intricately interrelated, but interpersonal relationships, trust, and effective communication are key conditions for evaluators and stakeholders wishing to promote EU.
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients. 相似文献
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones. 相似文献