Bootstrapping Monte Carlo Tree Search with an Imperfect Heuristic

We consider the problem of using a heuristic policy to improve the value approximation by the Upper Confidence Bound applied in Trees (UCT) algorithm in non-adversarial settings such as planning with large-state space Markov Decision Processes. Current improvements to UCT focus on either changing the action selection formula at the internal nodes or the rollout policy at the leaf nodes of the search tree. In this work, we propose to add an auxiliary arm to each of the internal nodes, and always use the heuristic policy to roll out simulations at the auxiliary arms. The method aims to get fast convergence to optimal values at states where the heuristic policy is optimal, while retaining similar approximation as the original UCT in other states. We show that bootstrapping with the proposed method in the new algorithm, UCT-Aux, performs better compared to the original UCT algorithm and its variants in two benchmark experiment settings. We also examine conditions under which UCT-Aux works well.Comment: 16 pages, accepted for presentation at ECML'1

A randomised, controlled, double blind, non-inferiority trial of ultrasound-guided fascia iliaca block vs. spinal morphine for analgesia after primary hip arthroplasty

We performed a single centre, double blind, randomised, controlled, non-inferiority study comparing ultrasound-guided fascia iliaca block with spinal morphine for the primary outcome of 24-h postoperative morphine consumption in patients undergoing primary total hip arthroplasty under spinal anaesthesia with levobupivacaine. One hundred and eight patients were randomly allocated to receive either ultrasound-guided fascia iliaca block with 2 mg.kg−1 levobupivacaine (fascia iliaca group) or spinal morphine 100 μg plus a sham ultrasound-guided fascia iliaca block using saline (spinal morphine group). The pre-defined non-inferiority margin was a median difference between the groups of 10 mg in cumulative intravenous morphine use in the first 24 h postoperatively. Patients in the fascia iliaca group received 25 mg more intravenous morphine than patients in the spinal morphine group (95% CI 9.0–30.5 mg, p < 0.001). Ultrasound-guided fascia iliaca block was significantly worse than spinal morphine in the provision of analgesia in the first 24 h after total hip arthroplasty. No increase in side-effects was noted in the spinal morphine group but the study was not powered to investigate all secondary outcomes

Synergistic action of dual IGF1/R and MEK inhibition sensitizes childhood acute lymphoblastic leukemia (ALL) cells to cytotoxic agents and involves downregulation of STAT6 and PDAP1.

Heterogeneous upregulation of multiple prosurvival pathways underlies resistance to damage-induced apoptosis in acute lymphoblastic leukemia (ALL) cells despite normal p53 responses. Here, we show that the dual combination of insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1/R) and mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition using AG1024 + U0126 can sensitize apoptosis-resistant ALL cells to ionizing radiation-induced DNA damage irrespective of effect of single pathway inhibition in vitro. This AG1024 + U0126 combination also significantly potentiates the ability of the core chemotherapy compounds vincristine, dexamethasone, and daunorubicin to kill ALL cells in vitro. Evidence of the synergistic action of AG1024 + U0126 in samples with variable basal levels of phosphorylated IGF1/Rβ and ERK1/2 suggested additional targets of this drug combination. Consistent with this, gene expression profiling identified 32 "synergy genes" differentially targeted by IGF1/R + MEK inhibition and, among these, Signal transducer and activator of transcription 6 (STAT6) and platelet-derived growth factor-associated protein 1 (PDAP1) were the most differentially downregulated cluster. Pearson correlation analyses revealed that STAT6 and PDAP1 display significant expression codependency and a common expression pattern linked with other key "synergy" genes, supporting their predicted role in an STAT6-ERK-nuclear factor kappa beta (NF-κB) network. Knockdown studies revealed that loss of STAT6, but not PDAP1, impinges on the cell cycle, causing reduced numbers of viable cells. In combination with daunorubicin, STAT6 loss has an additive effect on cell killing, whereas PDAP1 loss is synergistic, indicating an important role of PDAP1 in the cellular response to this anthracycline. Inhibition of STAT6 or PDAP1 may therefore represent a potential novel therapeutic strategy for resistant ALL by enhancing sensitivity to chemotherapy

Developing a Forensic Continuous Audit Model

Despite increased attention to internal controls and risk assessment, traditional audit approaches do not seem to be highly effective in uncovering the majority of frauds. Less than 20 percent of all occupational frauds are uncovered by auditors. Forensic accounting has recognized the need for automated approaches to fraud analysis yet research has not examined the benefits of forensic continuous auditing as a method to detect and deter corporate fraud. The purpose of this paper is to show how such an approach is possible. A model is presented that supports the acceptance of forensic continuous auditing by auditors and management as an effective tool to support the audit function, meet management’s regulatory objectives, and to combat fraud. An approach to developing such a system is presented