A rebate of 54.4% was needed for nivolumab to reach the ICER threshold. For scenario 2, 1.93 QALYs at AU$111,418 was estimated for nivolumab and 1.60 QALYs at AU$31,942 for everolimus with an ICER of AU$213,320/QALY gained. The rebate needed to reach the ICER threshold was 54.9%. One-way sensitivity analyses for both scenarios showed that the cost of nivolumab, time horizon and utilities were main drivers. The cost-effectiveness acceptability curves highlighted the differences in cost-effectiveness of the two scenarios, as well as significant uncertainty in the results.Conclusions A 54% rebate of the published price is needed for nivolumab to be cost-effective in Australia for the treatment of RCC. At that rebate, nivolumab remains cost-effective despite severe price erosion of everolimus because of improved longer term follow-up data. We recommend that generic price erosion should be accounted for when performing cost-effectiveness analysis.Background The objective of this study was to conduct a cost-effectiveness analysis of PCV13 vs. PPV23 and no vaccination and PPV23 vs. no vaccination in adults aged ≥ 60 years with underlying medical conditions which put them at an elevated risk of pneumococcal disease in a Japanese healthcare setting.Research design and methods A natural history model was developed with a life-long time horizon and 1-year cycle length, with microsimulation as a modeling technique. The expected costs from a public payer's and societal perspective, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by IPD (invasive pneumococcal disease) and NBP (non-bacteremic pneumococcal pneumonia) were estimated.Results In the base-case scenario, the cost per QALY gained from a public payer's perspective for PCV13 vs, PPV23 and no vaccination were 500,255JPY and 1,139,438JPY, respectively, The cost per QALY gained for PPV23 vs no vaccination was 1,687,057JPY. Over the life-long time horizon for 1 million patients, when compared to PPV23, PCV13 resulted in 65 fewer IPD cases, 2,894 fewer NBP cases, and 384 fewer deaths caused by pneumococcal disease.Conclusions In adults aged 60 years and over with underlying medical conditions, PCV13 was shown to be a more cost-effective alternative to PPV23. Proton computed tomography (pCT) and radiography (pRad) are proposed modalities for improved treatment plan accuracy and treatment validation in proton therapy. The pCT system of the Bergen pCT collaboration is able to handle very high particle intensities by means of track reconstruction. However, incorrectly reconstructed and secondary tracks degrade the image quality. We have investigated whether a convolutional neural network (CNN)-based filter is able to improve the image quality. The CNN was trained by simulation and reconstruction of tens of millions of proton and helium tracks. The CNN filter was then compared to simple energy loss threshold methods using the Area Under the Receiver Operating Characteristics curve (AUROC), and by comparing the image quality and Water Equivalent Path Length (WEPL) error of proton and helium radiographs filtered with the same methods. The CNN method led to a considerable improvement of the AUROC, from 74.3% to 97.5% with protons and from 94.2% to 99.5% with helium. The CNN filtering reduced the WEPL error in the helium radiograph from 1.03 mm to 0.93 mm while no improvement was seen in the CNN filtered pRads. The CNN improved the filtering of proton and helium tracks. Only in the helium radiograph did this lead to improved image quality.The CNN improved the filtering of proton and helium tracks. ERAS-0015 Only in the helium radiograph did this lead to improved image quality. To evaluate the impact of the planning target volume (PTV) density on treatment planning for lung Stereotactic Body Radiation Therapy (SBRT). The PTV coverage was analyzed in two groups of 40 lung SBRT patients. One group had PTV density <0.5 g/cm , while the other group had PTV density >0.5 g/cm . The treatments were planned in Pinnacle 9.10, using the collapsed cone convolution (CCC) algorithm. The prescribed dose was 60 Gy to the PTV in 4-8 fractions. Respecting constraint for the PTV coverage (D98% > 95%), we compared changes in the isodose line prescription, the number of monitor units (MU), maximum dose ( ), irradiated volume covered with 30 Gy ( ), and the optimization planning volume (OPV). For the same median values of the PTV coverage (98.3%), the differences are presented with median values between lower and higher density than 0.5 g/cm . The isodose line prescription was 83 90% (  < 0.0001), the MUs were 2294 1655 MU (  < 0.0001), was 74.26 68.09 Gy (  < 0.0001), was 117.03 104.81 cc (  = 0.04), and OPV was 28.48 39.35 cc (  < 0.001). By overriding the ITV density to 0.8 g/cm , the isodose line prescription decreases. The and MUs decrease by 7%, by 34%, and OPV by 70%. To obtain similar PTV coverage for PTV which is <0.5 g/cm , a larger margin irradiating a large OPV was used. More MUs and a higher maximum dose were delivered. For the PTV density of ≤0.36 g/cm overriding is recommended to reduce the dose and irradiated volume.To obtain similar PTV coverage for PTV which is less then 0.5 g/cm3, a larger margin irradiating a large OPV was used. More MUs and a higher maximum dose were delivered. For the PTV density of ≤0.36 g/cm3, overriding is recommended to reduce the dose and irradiated volume.Individual variation of the hypothalamic-pituitary-adrenal (HPA) axis response to stress could contribute to variable stress resiliency of livestock. During stress events, the innate immune system can also become activated and work in concert with the neuroendocrine system to restore homeostasis, while minimizing tissue damage. The purpose of this study was to assess immune function in variable stress-responding sheep in response to bacterial lipopolysaccharide (LPS) endotoxin immune-challenge. High (HSR, n = 12), middle (MSR, n = 12), and low-stress responders (LSR, n = 12) were selected from a population of 112 female lambs and classified based on serum cortisol concentration after receiving an intravenous bolus of LPS (400 ng/kg). Blood was collected from the jugular vein at 0 and 4 hrs post-LPS challenge to monitor changes in serum pro- and anti-inflammatory cytokines and chemokines, and white blood cell populations. Rectal temperature was recorded hourly to monitor fever. HSR had the greatest increase in rectal temperature and strongest pro-inflammatory IL-6 and IFN-γ cytokine responses compared to MSR and LSR.