Analyzing differences in the costs of treatment across centers within economic evaluations

Objectives: Assessments of health technologies increasingly include economic evaluations conducted alongside clinical trials. One particular concern with economic evaluations conducted alongside clinical trials is the generalizability of results from one setting to another. Much of the focus relating to this topic has been on the generalizability of results between countries, However, the characteristics of clinical trial design require further consideration of the generalizability of cost data between centers within a single country, which could be important in decisions about adoption of the new technology. Methods: We used data from a multicenter clinical trial conducted in the United Kingdom to assess the degree of variation in costs between patients and between treatment centers and the determinants of the degree of such variation. Results: The variation between patients was statistically significant for both the experimental and conventional treatments. However, the degree of variation between centers was only statistically significant for the experimental treatment. Such variation appeared to be a result of hospital practice, such as pay ment mechanisms for staff and provision of hostel accommodation, rather than variations in physical resource use or substantive differences in cost structure. Conclusions: Multicenter economic evaluations are necessary for determining the variations in hospital practice and characteristics that can in turn determine the generalizability of study results to other settings. Such analyses can identify issues that may be important in adopting a new health technology. Analysis is required of similar large multicenter trials to confirm these conclusions

Stabilization, pointing and command control of a balloon-borne 1-meter telescope

A 1-meter balloon-borne telescope has been constructed and flown to observe far-infrared radiation from celestial sources. The attitude control systems must perform to the diffraction limit of the telescope for stabilization and have positioning capability for source acquisition. These and associated systems are discussed in detail, as is the command control of the payload as a whole

Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi

Ergot alkaloids, indole-derived mycotoxins, interact with multiple monoamine neurotransmitter receptors and cause disease in exposed individuals. They have been well studied in the ergot fungus, Claviceps purpurea, and have been reported in some closely related grass endophytes, as well as the distantly related opportunistic human pathogen Aspergillus fumigatus. A. fumigatus, which sporulates prolifically, produces clavines, specifically festuclavine and fumigaclavines A, B, and C in association with asexual spores and the total mass of alkaloids constitutes over 1% of the spore mass. These alkaloids differ from those of most clavicipitaceous fungi, which consist of different clavines and often more complex lysergic acid derivatives. However, the ergot alkaloid pathways of A. fumigatus and ergot fungi are hypothesized to share early biosynthetic steps, diverging at some point after the formation of the intermediate chanoclavine. A homologue of dmaW, a gene encoding dimethylallyltryptophan synthase in Neotyphodium endophytes, was found in the A. fumigatus genome. By gene knockout analysis, dmaW was shown to be required for ergot alkaloid production in A. fumigatus. Comparison of genes clustered around A. fumigatus dmaW to those clustered with dmaW in the ergot fungi revealed potential homologues that could encode proteins controlling early, shared steps in the pathway. Functional analysis via gene knockout of three additional A. fumigatus genes (easA, easE, and easF) rendered mutants with altered alkaloid profiles, demonstrating their involvement in ergot alkaloid biosynthesis. All mutants lacked normal ergot alkaloid production from the latter part of the pathway; complementation with a functional copy of the respective gene, restored normal ergot alkaloid production in each mutant. Analyses of intermediates positioned the products of easF and easE as the second and third enzymatic steps of the pathway. Knockout of easA caused accumulation of multiple intermediates, including chanoclavine; complementation with the C. purpurea easA gene resulted in accumulation of agroclavine, setoclavine, and its isomer isosetoclavine. These data confirm easA involvement post chanoclavine synthesis and more specifically assign its role to reduction of chanoclavine aldehyde, the branch point of the two lineage-specific pathways. These mutants, due to their differing ergot alkaloid profiles, are valuable for testing the role of specific ergot alkaloids in animal pathogenesis and toxicoses. Elucidation of ergot alkaloid biosynthesis, along with the capacity to control the spectrum of alkaloids produced, may be beneficial to agriculture and medicine. Additional studies demonstrated that production of ergot alkaloids was restricted to conidiating cultures. Disruption of brlA, a regulatory gene involved in conidiation, interfered with conidiophore development, as well as ergot alkaloid production. The association of these toxins with sporulation may offer insight into their ecological significance and utility to the fungus

Deepening the Call to Ministry through Narrative Spiritual Practice

Through exploring literature on spiritual practice and narrative practice, this article lifts up the discovery that, to the contrary, telling one's story of call is challenging, difficult, and often tied to multiple stories. Through the narrative persons can explor their stories of their call and deepen their call through sharing

Introduction to the special issue on L2 writing and feedback processing and use in pen and paper and digital environments: Advancing research and practice

The present special issue (SI) is a collection of position papers and empirical studies intended to advance disciplinary conversations on the learning and teaching of second or foreign language (L2) writing in instructed second language acquisition (ISLA) contexts. It does so by analyzing critically past research, providing new empirical insights obtained in controlled and classroom-based studies conducted in various educational settings with diverse populations, suggesting worthy avenues to be pursued in future research agendas, and drawing implications for practice

EQUIPT: protocol of a comparative effectiveness research study evaluating cross-context transferability of economic evidence on tobacco control

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.This article has been made available through the Brunel Open Access Publishing Fund.Tobacco smoking claims 700 000 lives every year in Europe and the cost of tobacco smoking in the EU is estimated between €98 and €130 billion annually; direct medical care costs and indirect costs such as workday losses each represent half of this amount. Policymakers all across Europe are in need of bespoke information on the economic and wider returns of investing in evidence-based tobacco control, including smoking cessation agendas. EQUIPT is designed to test the transferability of one such economic evidence base-the English Tobacco Return on Investment (ROI) tool-to other EU member states