International lease accounting reform and economic consequences: the views of UK users and preparers

In response to perceived difficulties with extant lease-accounting standards in operation worldwide, the G4+1 issued a discussion paper which proposes that all leases should be recognized on the balance sheet [ASB (1999). Leases: Implementation of a new approach, discussion paper. London: Accounting Standards Board]. Leasing is now on the active agenda of the IASB. A major difficulty faced by standard setters lies in overcoming the preparer/user lobbying imbalance and obtaining ex ante evidence on the likely impact of regulatory reform. This paper contributes to the ongoing international debate by conducting a questionnaire survey of U.K. users and preparers to assess their views on proposals for lease-accounting reform and on the potential economic consequences of their adoption. The results, based on 132 responses, indicate that both groups accept that there are deficiencies in the current rules, but they do not agree on the way forward and believe that the proposals would lead to significant economic consequences for key parties. The impact on respondents' views of familiarity with the proposals, level of lease usage, and company size, is also examined

Kine-Mould: Flexible mould system opens up wide range of possibilities

The Kine-Mould is a development that makes it easier to manufacture building elements with complex geometry. Since June 2014 the team has been working on a range of solutions and prototypes. Various building materials have been investigated such as concrete, glass and plastic composites. In a joint effort of TU Delft and TU Eindhoven the following prototypes were designed and built:One for thermoplastic polymers;One for concrete elements;One for glass elements;Several for inflatable mould surfaces.Students carried out a significant part of the work. Companies were involved in the manufacturing process of the prototypes and application of the results

Modeling Patient-Specific Dose-Function Response for Enhanced Characterization of Personalized Functional Damage

PURPOSE: Functional-guided radiation therapy (RT) plans have the potential to limit damage to normal tissue and reduce toxicity. Although functional imaging modalities have continued to improve, a limited understanding of the functional response to radiation and its application to personalized therapy has hindered clinical implementation. The purpose of this study was to retrospectively model the longitudinal, patient-specific dose-function response in non-small cell lung cancer patients treated with RT to better characterize the expected functional damage in future, unknown patients. METHODS AND MATERIALS: Perfusion single-photon emission computed tomography/computed tomography scans were obtained at baseline (n = 81), midtreatment (n = 74), 3 months post-treatment (n = 51), and 1 year post-treatment (n = 26) and retrospectively analyzed. Patients were treated with conventionally fractionated RT or stereotactic body RT. Normalized perfusion single-photon emission computed tomography voxel intensity was used as a surrogate for local lung function. A patient-specific logistic model was applied to each individual patient's dose-function response to characterize functional reduction at each imaging time point. Patient-specific model parameters were averaged to create a population-level logistic dose-response model. RESULTS: A significant longitudinal decrease in lung function was observed after RT by analyzing the voxelwise change in normalized perfusion intensity. Generated dose-function response models represent the expected voxelwise reduction in function, and the associated uncertainty, for an unknown patient receiving conventionally fractionated RT or stereotactic body RT. Differential treatment responses based on the functional status of the voxel at baseline suggest that initially higher functioning voxels are damaged at a higher rate than lower functioning voxels. CONCLUSIONS: This study modeled the patient-specific dose-function response in patients with non-small cell lung cancer during and after radiation treatment. The generated population-level dose-function response models were derived from individual patient assessment and have the potential to inform functional-guided treatment plans regarding the expected functional lung damage. This type of patient-specific modeling approach can be applied broadly to other functional response analyses to better capture intrapatient dependencies and characterize personalized functional damage

Routine follow-up radiographs for distal radius fractures are seldom clinically substantiated

Introduction: The value of routine radiographs during follow-up after distal radius fractures is unclear. The aim of this study was to evaluate whether routine radiographs performed during the follow-up period in patients with a distal radius fracture influenced clinical decision making. Methods: This retrospective cohort study included patients aged ≥18 years who were treated for a distal radius fracture at four hospitals in The Netherlands in 2012. Demographic and clinical and radiographic characteristics were collected from medical records. Results: 1042 patients were included. In 121 (14%) of the 841 radiographs, a clinical indication was reported. Treatment was affected by 22 (2.6%) radiographs, including 11 (1.5%) radiographs that were categorized as routine, 9 (1.2%) of which led to prolonged cast immobilization and 2 (0.2%) to surgery for conservatively treated patients. Conclusion: Although it is common practice to take radiographs after distal radius fractures, the study results indicate that routine radiographs seldom affect treatment. This finding should be weighed against the high health care costs associated with these fractures. We hope that the results of our study will trigger the awareness among surgeons that in the current practice, many radiographs are taken on routine without influencing clinical decision making and can probably be omitted. Level of evidence: Level III

2-D Magnetohydrodynamic Simulations of Induced Plasma Dynamics in the Near-Core Region of a Galaxy Cluster

We present results from numerical simulations of the cooling-core cluster A2199 produced by the two-dimensional (2-D) resistive magnetohydrodynamics (MHD) code MACH2. In our simulations we explore the effect of anisotropic thermal conduction on the energy balance of the system. The results from idealized cases in 2-D axisymmetric geometry underscore the importance of the initial plasma density in ICM simulations, especially the near-core values since the radiation cooling rate is proportional to ${n_e}^2$. Heat conduction is found to be non-effective in preventing catastrophic cooling in this cluster. In addition we performed 2-D planar MHD simulations starting from initial conditions deliberately violating both thermal balance and hydrostatic equilibrium in the ICM, to assess contributions of the convective terms in the energy balance of the system against anisotropic thermal conduction. We find that in this case work done by the pressure on the plasma can dominate the early evolution of the internal energy over anisotropic thermal conduction in the presence of subsonic flows, thereby reducing the impact of the magnetic field. Deviations from hydrostatic equilibrium near the cluster core may be associated with transient activity of a central active galactic nucleus and/or remnant dynamical activity in the ICM and warrant further study in three dimensions.Comment: 16 pages, 13 figures, accepted for publication in MNRA

Costes de adaptación a los impactos del cambio climático en sistemas hídricos: Estimaciones existentes y retos para la investigación

[EN] Information on the cost of adaptation in freshwater systems is necessary to better design strategies to face climate change and water management. We look at the existing estimates with the aim of identifying research gaps. Our analysis shows that case study-specific literature is scarce, fragmented, and not always methodologically transparent. At the same time, most existing global assessments are likely to represent underestimates and rely heavily on each other. We conclude that a clear conceptual framework is still missing. Remaining research gaps include addressing inter-sector linkages and estimations of other than only direct costs, in addition to addressing the issues of ‘adaptation deficit’ and ‘residual damage’.[ES] Tener información sobre los costes de adaptación en sistemas hídricos es necesario para un mejor diseño de estrategias de cambio climático y gestión hídrica. En este artículo se analizan las estimaciones existentes en la literatura con el fin de identificar los retos para la investigación. Nuestro análisis pone de manifiesto que la literatura focalizada en casos de estudio específicos es escasa, es fragmentaria y no siempre es transparente en cuanto a su metodología. Asimismo, las evaluaciones globales existentes representan probablemente una subestimación de los costes y además se trata de estimaciones interdependientes. Concluimos que falta desarrollar un marco conceptual para la estimación de los costes de adaptación y que la investigación futura debe preocuparse por el análisis de costes más allá de los costes directos y por las relaciones intersectoriales; así como por el ‘déficit de adaptación’ y el ‘daño residual’.Martín-Ortega, J. (2011). Costs of adaptation to climate change impacts on fresh-water systems: existing estimates and research gaps. 5-28. https://doi.org/10.7201/earn.2011.01.01SWORD52

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis

Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targetable RP2 pathway. In a prospective clinical trial of response-adapted RT for patients (n = 39) with locally advanced non-small cell lung cancer, we analyzed patients\u27 plasma, collected pre- and during RT, for microRNAs (miRNAs) and cytokines using array and multiplex enzyme linked immunosorbent assay (ELISA), respectively. Interactions between candidate biomarkers, radiobiological, and clinical parameters were analyzed using data-driven Bayesian network (DD-BN) analysis. We identified alterations in specific miRNAs (miR-532, -99b and -495, let-7c, -451 and -139-3p) correlating with lung toxicity. High levels of soluble tumor necrosis factor alpha receptor 1 (sTNFR1) were detected in a majority of lung cancer patients. However, among RP patients, within 2 weeks of RT initiation, we noted a trend of temporary decline in sTNFR1 (a physiological scavenger of TNFα) and ADAM17 (a shedding protease that cleaves both membrane-bound TNFα and TNFR1) levels. Cytokine signature identified activation of inflammatory pathway. Using DD-BN we combined miRNA and cytokine data along with generalized equivalent uniform dose (gEUD) to identify pathways with better accuracy of predicting RP2 as compared to either miRNA or cytokines alone. This signature suggests that activation of the TNFα-NFκB inflammatory pathway plays a key role in RP which could be specifically ameliorated by etanercept rather than current therapy of non-specific leukotoxic corticosteroids

Reduction of routine use of radiography in patients with ankle fractures leads to lower costs and has no impact on clinical outcome: an economic evaluation

Background: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures.Methods: We performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping.Results: In total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was - 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (-(sic)48; 95% CI:- (sic)72 to -(sic)25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of (sic)20,000 per QALY.Conclusions: Reducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs.Trauma Surger