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Patients with hematological malignancies are at high risk of infections due to both the disease and the associated treatments. The use of immunoglobulin (Ig) to prevent infections is increasing in this population, but its cost effectiveness is unknown. This trial-based economic evaluation aimed to compare the cost effectiveness of prophylactic Ig with prophylactic antibiotics in patients with hematological malignancies.
Methods
The economic evaluation used individual patient data from the RATIONAL feasibility trial, which randomly assigned 63 adults with chronic lymphocytic leukemia, multiple myeloma, or lymphoma to prophylactic Ig or prophylactic antibiotics. The following two analyses were conducted to estimate the cost effectiveness of the two treatments over the 12-month trial period from the perspective of the Australian health system:
(i) a cost-utility analysis (CUA) to assess the incremental cost per quality-adjusted life-year (QALY) gained using data collected with the EuroQol 5D-5L questionnaire; and
(ii) a cost-effectiveness analysis (CEA) to assess the incremental cost per serious infection prevented (grade ≥3) and per infection prevented (any grade).
Results
The total cost per patient was significantly higher in the Ig arm than in the antibiotic arm (difference AUD29,140 [USD19,000]). There were non-significant differences in health outcomes between the treatment arms: patients treated with Ig had fewer QALYs (difference −0.072) and serious infections (difference −0.26) than those given antibiotics, but more overall infections (difference 0.76). The incremental cost-effectiveness from the CUA indicated that Ig was more costly than antibiotics and associated with fewer QALYs. In the CEA, Ig costed an additional AUD111,262 (USD73,000) per serious infection prevented, but it was more costly than antibiotics and associated with more infections when all infections were included.
Conclusions
These results indicate that, on average, Ig prophylactic treatment may not be cost effective compared with prophylactic antibiotics for the group of patients with hematological malignancies recruited to the RATIONAL feasibility trial. Further research is needed to confirm these findings in a larger population and over the longer term.
The rotorcraft is a complex dynamical system that demands specialist modelling skills, and a high level of understanding of the aeromechanics arising from the main rotor wake and aerodynamic couplings. One such example is the difficulty predicting off-axis responses, particularly in hover and low-speed flight, associated with induced velocity variation through the rotor disk resulting from the rotor wake distortions. Various approaches have been developed to deal with this phenomenon but usually demand prerequisites of high levels of expertise and profound aerodynamic knowledge. This paper presents a new and practical approach to capturing this wake distortion through an augmented rotor inflow model. The proposed model is coupled with a nonlinear simulation using the FLIGHTLAB environment, and comparisons are made between the simulation results and flight test data from the National Research Council of Canada’s Advanced System Research Aircraft in hover and low speed. Results show good predictability of the proposed nonlinear model structure, demonstrated by its capability to closely match the time responses to multi-step control inputs from flight test. The results reported are part of ongoing research at Liverpool and Cranfield University into rotorcraft simulation fidelity.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The challenges to global order posed by rapid environmental change are increasingly recognized as defining features of our time. In this groundbreaking work, the concept of innovation is deployed to explore normative and institutional responses in international law to such environmental change by addressing two fundamental themes: first, whether law can foresee, prevent, and adapt to environmental transformations; and second, whether international legal responses to social, economic, and technological innovation can appropriately reflect the evolving needs of contemporary societies at national and international scales. Using a range of case studies, the contributions to this collection track innovation - descriptively, normatively, and as a process in and of itself - to explain international environmental law's functionality in the Anthropocene. This book should be read by anyone interested in the critical intersection of environmental and international law.
Modelling the hydrology of the Greenland ice sheet, including the filling and drainage of supraglacial lakes, requires melt inputs generated at high spatial and temporal resolution. Here we apply a high spatial (100 m) and temporal (1 hour) mass-balance model to a 450 km2 subset of the Paakitsoq region, West Greenland. The model is calibrated by adjusting the values for parameters of fresh snow density, threshold temperature for solid/liquid precipitation and elevation-dependent precipitation gradient to minimize the error between modelled output and surface height and albedo measurements from three Greenland Climate Network stations for the mass-balance years 2000/01 and 2004/05. Bestfit parameter values are consistent between the two years at 400 kg m-3, 2°C and +14% (100 m)-1, respectively. Model performance is evaluated, first, by comparing modelled snow and ice distribution with that derived from Landsat-7 ETM+ satellite imagery using normalized-difference snow index classification and supervised image thresholding; and second, by comparing modelled albedo with that retrieved from the MODIS sensor M0D10A1 product. Calculation of mass-balance components indicates that 6% of surface meltwater and rainwater refreezes in the snowpack and does not become runoff, such that refreezing accounts for 31% of the net accumulation.
Our principal focus in this paper is on ways that a Fast Close process (or indeed any reserving process) can be structured to maximise the value added within the process given the time and resource available. This builds on the use of actual vs. expected techniques investigated in our previous paper, and also looks at forces external to the reserving function that may derail smooth progress. We highlight a number of practical ways that the balance can be restored in favour of adding value rather than crunching numbers. This paper forms the second in the TORP series.