Development in Aspergillus

AbstractThe genus Aspergillus represents a diverse group of fungi that are among the most abundant fungi in the world. Germination of a spore can lead to a vegetative mycelium that colonizes a substrate. The hyphae within the mycelium are highly heterogeneous with respect to gene expression, growth, and secretion. Aspergilli can reproduce both asexually and sexually. To this end, conidiophores and ascocarps are produced that form conidia and ascospores, respectively. This review describes the molecular mechanisms underlying growth and development of Aspergillus

On the (not so) constant proportional trade-off in TTO

Abstract. Purpose: The linear and power QALY models require that people in Time Trade-off (TTO) exercises sacrifice the same proportion of lifetime to obtain a health improvement, irrespective of the absolute amount. However, evidence on these constant proportional trade-offs (CPTOs) is mixed, indicating that these versions of the QALY model do not represent preferences. Still, it may be the case that a more general version of the QALY model represents preferences. This version has the property that people want to sacrifice the same proportion of utilities of lifetime for a health improvement, irrespective of the amount of this lifetime. Methods: We use a new method to correct TTO scores for utility of life duration and test whether decision makers trade off utility of duration and quality at the same rate irrespective of duration. Results: We find a robust violation of CPTO for both uncorrected and corrected TTO scores. Remarkably, we find higher values for longer durations, contrary to most previous studies. This represents the only study correcting for utility of life duration to find such a violation. Conclusions: It seems that the trade-off of life years is indeed not so constantly proportional and, therefore, that health state valuations depend on durations

Easy implementation of advanced tomography algorithms using the ASTRA toolbox with Spot operators

Mathematical scripting languages are commonly used to develop new tomographic reconstruction algorithms. For large experimental datasets, high performance parallel (GPU) implementations are essential, requiring a re-implementation of the algorithm using a language that is closer to the computing hardware. In this paper, we introduce a new Matlab interface to the ASTRA toolbox, a high performance toolbox for building tomographic reconstruction algorithms. By exposing the ASTRA linear tomography operators through a standard Matlab matrix syntax, existing and new reconstruction algorithms implemented in Matlab can now be applied directly to large experimental datasets. This is achieved by using the Spot toolbox, which wraps external code for linear operations into Matlab objects that can be used as matrices. We provide a series of examples that demonstrate how this Spot operator can be used in combination with existing algorithms implemented in Matlab and how it can be used for rapid development of new algorithms, resulting in direct applicability to large-scale experimental datasets

A Multi-Channel DART algorithm

Tomography deals with the reconstruction of objects from their projections, acquired along a range of angles. Discrete tomography is concerned with objects that consist of a small number of materials, which makes it possible to compute accurate reconstructions from highly limited projection data. For cases where the allowed intensity values in the reconstruction are known a priori, the discrete algebraic reconstruction technique (DART) has shown to yield accurate reconstructions from few projections. However, a key limitation is that the benefit of DART diminishes as the number of different materials increases. Many tomographic imaging techniques can simultaneously record tomographic data at multiple channels, each corresponding to a different weighting of the materials in the object. Whenever projection data from more than one channel is available, this additional information can potentially be exploited by the reconstruction algorithm. In this paper we present Multi-Channel DART (MC-DART), which deals effectively with multi-channel data. This class of algorithms is a generalization of DART to multiple channels and combines the information for each separate channel-reconstruction in a multi-channel segmentation step. We demonstrate that in a range of simulation experiments, MC-DART is capable of producing more accurate reconstructions compared to single-channel DART

Measuring loss aversion under ambiguity: a method to make prospect theory completely observable

We propose a simple, parameter-free method that, for the first time, makes it possible to completely observe Tversky and Kahneman’s (1992) prospect theory. While methods exist to measure event weighting and the utility for gains and losses separately, there was no method to measure loss aversion under ambiguity. Our method allows this and thereby it can measure prospect theory’s entire utility function. Consequently, we can properly identify properties of utility and perform new tests of prospect theory. We implemented our method in an experiment and obtained support for prospect theory. Utility was concave for gains and convex for losses and there was substantial loss aversion. Both utility and loss aversion were the same for risk and ambiguity, as assumed by prospect theory, and sign-comonotonic trade-off consistency, the central condition of prospect theory, held

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS: Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS: (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION: This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors

Australian utility weights for the EORTC QLU-C10D, a multi-attribute utility instrument derived from the cancer-specific quality of life questionnaire, EORTC QLQ-C30

Background: The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely-used cancer-specific quality of life questionnaire, EORTC QLQ-C30. The QLU-C10D contains ten dimensions (Physical, Role, Social and Emotional Functioning; Pain, Fatigue, Sleep, Appetite, Nausea, Bowel Problems), each with 4 levels. To be used in cost-utility analysis, country-specific valuation sets are required. Objective: To provide Australian utility weights for the QLU-C10D. Methods: An Australian online panel was quota sampled to ensure population representativeness by sex and age (≥18y). Participants completed a discrete choice experiment (DCE) consisting of 16 choice-pairs. Each pair comprised two QLU-C10D health states plus life expectancy. Data were analysed using conditional logistic regression, parameterised to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each QOL dimension-level coefficient to the coefficient on life expectancy. Results: 1979 panel members opted-in, 1904 (96%) completed at least one choice-pair, and 1846 (93%) completed all 16 choice-pairs. Dimension weights were generally monotonic: poorer levels within each dimension were generally associated with greater utility decrements. The dimensions that impacted most on choice were, in order, Physical Functioning, Pain, Role Functioning and Emotional Functioning. Oncology-relevant dimensions with moderate impact were Nausea and Bowel Problems. Fatigue, Trouble Sleeping and Appetite had relatively small impact. The value of the worst health state was -0.096, somewhat worse than death. Conclusions: This study provides the first country-specific value set for the QLU-C10D, which can facilitate cost-utility analyses when applied to data collected with the EORTC QLQ-C30, prospectively and retrospectively