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editorial

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be “all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty”. The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.

A DNA template containing a single ethyl phosphotriester was replicated in vitro by the bacteriophage T4 DNA polymerase and by Escherichia coli DNA polymerase I (DNA pol I). Escherichia coli DNA pol I bypassed the lesion ef®ciently, but partial inhibition was observed for T4 DNA polymerase. The replication block produced by the ethyl phosphotriester was increased at low dNTP concentrations and for a mutant T4 DNA polymerase with an antimutator phenotype, increased proofreading activity, and reduced ability to bind DNA in the polymerase active center. These observations support a model in which an ethyl phosphotriester impedes primer elongation by T4 DNA polymerase by decreasing formation of the ternary DNA polymerase±DNA± dNTP complex. When primer elongation is not possible, proofreading becomes the favored reaction. Apparent futile cycles of nucleotide incorporation and proofreading, the idling reaction, were observed at the site of the lesion. The replication block was overcome by higher dNTP concentrations. Thus, ethyl phosphotriesters may be tolerated in vivo by the up-regulation of dNTP biosynthesis that occurs during the cellular checkpoint response to blocked DNA replication forks.

During my life, I have spent a great deal of time – some would argue far too much time – watching movies. And of the countless films I have seen, few have made more of an impression on me than Steven Spielberg’s 1998 masterpiece, Saving Private Ryan, which is generally regarded as one of the greatest movies of all time. Staff no

https://viurrspace.ca/bitstream/handle/10613/17324/Nov16-1898.pdf?sequence=2

Aim Predictions of spread of non-indigenous species allow for greater efficiency in managing invasions by targeting areas for preventative measures. The invasion sequence is a useful concept in predictions of spread, as it allows us to test hypotheses about the transport and establishment of propagules in novel habitats. Our aims are twofold: (1) to develop and validate multi-stage invasion models for the introduced fishhook waterflea, Cercopagis pengoi, and (2) to assess how variability in the transport patterns of the propagules influences the accuracy and spatial extent for predictions of spread. Location New York State, USA. Methods We developed a two-stage model for the spread of C. pengoi. First, we developed a stochastic gravity model for dispersal based on surveys of recreational boat traffic in New York State as a proxy for propagule pressure. We then modelled the probability of establishment based on predicted levels of propagule pressure and measures of lakes’ physicochemistry. In addition, we used Monte Carlo simulations based on the gravity model to propagate variability in boater traffic through the establishment model to assess how uncertainty in dispersal influenced predictions of spread. Results The amount recreationalists were willing to spend, lake area and population size of the city nearest to the destination lake were significant factors affecting boater traffic. In turn, boater traffic, lake area, specific conductance and turbidity were significant predictors of establishment. The inclusion of stochastic dispersal reduced the rate of false positives (i.e. incorrect prediction of an invasion) in detecting invasions at the upper 95% prediction interval for the probability of establishment. Main conclusions Combinations of measures of propagule pressure, habitat suitability and stochastic dispersal allow for the most accurate predictions of spread. Further, multi-stage spread models may overestimate the extent of spread if stochasticity in early stages of the models is not considered.

An issue of Review Revista Rundschau Revue journal. The text is in multiple languages. https://viurrspace.ca/bitstream/handle/10613/26519/Mac-291.pdf?sequence=3&isAllowed=y

Perceived control (Rothbaum, Weisz, & Snyder, 1982) and achievement goals (Dweck & Leggett, 1988) are two widely studied motivational constructs that influence students’ emotions and achievement. The central focus of this dissertation was to explore the associations between achievement goals and perceived control in three studies. Each study used a separate cohort of first-year college students taken from the Motivation and Academic Achievement (MAACH) Project (1992-2005, N = 10,053). Study 1 (n = 752) was descriptive and tested the associations between goals, control, and attributions. The results demonstrated that primary control was very clearly defined by the controllability dimension of attributions; however, the other variables were less clear. The purpose of Study 2 (n = 360) was to test for reciprocal relationships between goals and control by using a two-wave four-variable cross-lag panel model. The best predictor of each Time 2 variable was its corresponding Time 1 counterpart. Additionally, the results showed that Time 1 mastery goals positively predicted Time 2 primary and secondary control, but no other relationships emerged. Study 3 (n = 251) extended the relationships between goals and control to predict students’ emotions and achievement. The direct and indirect effects implied by the following longitudinal model were tested: goals → control → emotions → achievement (Pekrun, 2006). Mastery goals positively predicted primary and secondary control, whereas performance goals positively predicted primary control only. Primary control was the main mediator between goals and negative emotions. Additionally, primary control had a positive direct effect on achievement, and thus mediated the effects of both mastery and performance goals on this outcome. Secondary control had a negative direct effect on achievement and consequently acted as a negative mediator between mastery goals and achievement. For mastery goals, anger, anxiety, and boredom functioned as positive mediators with achievement. These emotions also positively mediated the effects of primary control on achievement. Results of the three studies are discussed in terms of contributions to the separate literatures on achievement goals and perceived control and in terms of implications for students in new and challenging achievement settings.