Arbitration between controlled and impulsive choices.

The impulse to act for immediate reward often conflicts with more deliberate evaluations that support long-term benefit. The neural architecture that negotiates this conflict remains unclear. One account proposes a single neural circuit that evaluates both immediate and delayed outcomes, while another outlines separate impulsive and patient systems that compete for behavioral control. Here we designed a task in which a complex payout structure divorces the immediate value of acting from the overall long-term value, within the same outcome modality. Using model-based fMRI in humans, we demonstrate separate neural representations of immediate and long-term values, with the former tracked in the anterior caudate (AC) and the latter in the ventromedial prefrontal cortex (vmPFC). Crucially, when subjects' choices were compatible with long-run consequences, value signals in AC were down-weighted and those in vmPFC were enhanced, while the opposite occurred when choice was impulsive. Thus, our data implicate a trade-off in value representation between AC and vmPFC as underlying controlled versus impulsive choice.

Concomitant use of direct-acting antivirals and chemotherapy in hepatitis C virus-infected patients with cancer.

BACKGROUND: Antiviral therapy improves hepatic outcomes in hepatitis C virus (HCV)-infected cancer patients. However, such patients are not treated simultaneously with antivirals and chemotherapy, owing to overlapping toxicities with previous standard of care treatment of pegylated interferon and ribavirin. AIM: To examine the safety and clinically-significant drug-drug interactions observed in patients who received simultaneous treatment with direct-acting antivirals (DAAs) and chemotherapy. METHODS: Safety was determined by the presence of adverse events which were graded according to the division of AIDS Table (version 2.0). Adverse events were monitored throughout antiviral treatment and up to 3 months after its completion. Drug-drug interactions were assessed using current online databases. Sustained virological response (SVR) was defined as absence of serum HCV RNA 12 weeks after end of DAA treatment. Cirrhosis was diagnosed via imaging, biopsy or with the use of non-invasive fibrosis markers. RESULTS: Twenty-one patients received concomitant treatment with DAAs and chemotherapy between January 2013 and September 2016. Concomitant treatment was started either for virological (14; 67%) or oncologic (7; 33%) reasons. DAAs used were sofosbuvir, ledipasvir, simeprevir, daclatasvir ± ribavirin. The adverse events observed were mainly constitutional (12; 57%), hematological and gastrointestinal (7; 33% each). Physicians changed the DAA regimens in two patients (10%) in anticipation of drug-drug interactions with daclatasvir and dexamethasone. The overall SVR rate was 95% (20/21). CONCLUSIONS: Hepatitis C virus-targeted antiviral therapy can be used concomitantly with selected anti-neoplastic agents under close monitoring for drug-drug interactions. This therapeutic intervention may prevent delay in the administration of chemotherapy in HCV-infected cancer patients.