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Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
Methods:
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Results:
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Conclusions:
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (${\sim}60\%$), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
In this discussion I shall argue that some fairly widely held views about human habits are mistaken. These misconceptions are important because of the pervasiveness of the habitual in human behavior and because it is the concept of habit that has served as the prototype of various conceptions of conditioned response which are used in psychological explanation. One major task of this analysis is to show that accounts in which actions are explained by reference to rules are not incompatible with accounts in which the same behavior is seen as the product of habit.
In an examination of Ryle's distinction between knowing how and knowing that D. G. Brown is led to the conclusion that “All knowing how is knowing that.” The distinction (in the form that Ryle drew it) is improper, and these tags should be dropped. All knowledge is propositional, after all, though there is a legitimate way of retaining the essentials of Ryle's account. Knowledge for which the primary evidence is a person's performance replaces the category of knowing how in this reformulated version of the distinction. But to have this type of knowledge is to know the answers to questions concerning the way in which it can be done. And this is knowing that.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
Objectives:
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
Methods:
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Results:
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Conclusions:
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Reduction of the pulse width has been reported to improve ECT outcomes with unilateral ECT (similar efficacy, fewer cognitive side effects), but has been minimally studied for bitemporal ECT. The only study comparing brief and ultrabrief pulse bitemporal ECT found reduced efficacy for bitemporal ultrabrief compared to bitemporal brief pulse stimulation. This randomised controlled trial (RCT) aimed to test if ultrabrief pulse bitemporal ECT results in fewer cognitive side effects than brief pulse bitemporal ECT, when given at doses adjusted with the aim of achieving comparable efficacy.
Methods
Thirty-six participants were randomly assigned to receive ultrabrief (at 3 times seizure threshold) or brief (at 1.5 times seizure threshold) pulse bitemporal ECT given 3 times a week in a double-blind, controlled proof-of-concept trial. Blinded raters assessed mood and cognitive functioning over the ECT course.
Results
Efficacy and cognitive outcomes did not differ significantly between the two treatment groups over the ECT course. The ultrabrief pulse group performed better on a test of visual memory assessed acutely after an ECT treatment.
Conclusions
This study suggests there may be a small cognitive advantage in giving bitemporal ECT with an ultrabrief pulse when dosage is increased to match the efficacy of brief pulse bitemporal ECT, but the study was underpowered to fully examine this issue.
Determining the best strategy for allocating weed management resources across and between landscapes is challenging because of the uncertainties and large temporal and spatial scales involved. Ecological models of invasive plant spread and control provide a practical tool with which to evaluate alternative management strategies at landscape scales. We developed a spatially explicit model for the spread and control of spotted knapweed and leafy spurge across three Montana landscapes. The objective of the model was to determine the ecological and economic costs and benefits of alternative strategies across landscapes of varying size and stages of infestation. Our results indicate that (1) in the absence of management the area infested will continue to increase exponentially leading to a substantial cost in foregone grazing revenues; (2) even though the costs of management actions are substantial, there is a net economic benefit associated with a broad range of management strategies; (3) strategies a that prioritize targeting small new infestations consistently outperform strategies that target large established patches; and (4) inconsistent treatment and short-term delays can greatly reduce the economic and ecological benefits of management.
In this paper I address a question that has not been a prominent feature of cases or articles which have concerned the issue of consent in relation to sexual offenses. Much work has been done by judges and legal theorists regarding the defendant’s beliefs about the consent of the complainant and the mental element or mens rea of this offense. But, any answers to these questions presuppose some answer to a prior question: What is consent? What must be true of a person who does consent? What must be missing, on the other hand, in a situation where sexual activity takes place without consent?
Common sense provides a relatively simple answer to these questions: To consent is to give permission; a person acts without consent where no such permission has been obtained. It is this answer that I want to defend in this paper. This view assumes that talk of consent only makes sense in relation to some autonomy right. Giving consent involves autonomously making changes in a prevailing pattern of rights and obligations. It is a limited withdrawal of a right not to be interfered with; and it will make legally permissible actions that would otherwise be subject to criminal and civil penalties. To me it seems obvious that such a change in the prevailing pattern of rights and obligations can only take place where there is communication between the parties. This means that the question of consent is not just a question about the state of mind or attitude of the complainant. Rather, the matter which should be central to a court’s consideration of consent is the question of what was said or done that could be construed as granting permission to do the acts in question.
Are justice and mercy incompatible with each other, so that it is unjust for a judge to be merciful? In a recent article Jeffrie Murphy generates and explores some interesting paradoxes concerning the virtue (or supposed virtue) of mercy. Murphy argues for a skeptical position concerning mercy in relation to criminal justice: mercy has no place in the sentencing decisions of judges
This paper focuses on Quebec language legislation which has the effect of prohibiting the use of the use of English on signs. The controversial “Frenchonly” sign law is considered in spelling out an argument for collective rights and assessing some of the obstacles which a collective rights thesis must overcome. No attempt is made in this discussion to resolve the question of the relative weight of the collective and individual rights which come into conflict in this situation. No doubt this latter is itself a difficult task. If the argument of this paper is sound, however, a solution phrased wholly in terms of individual rights and the public good is simpler only because it omits important dimensions of the problem.
We examined caregiver report of externalizing behavior from 12 to 54 months of age in 102 children randomized to care as usual in institutions or to newly created high-quality foster care. At baseline no differences by group or genotype in externalizing were found. However, changes in externalizing from baseline to 42 months of age were moderated by the serotonin transporter linked polymorphic region genotype and intervention group, where the slope for short–short (S/S) individuals differed as a function of intervention group. The slope for individuals carrying the long allele did not significantly differ between groups. At 54 months of age, S/S children in the foster care group had the lowest levels of externalizing behavior, while children with the S/S genotype in the care as usual group demonstrated the highest rates of externalizing behavior. No intervention group differences were found in externalizing behavior among children who carried the long allele. These findings, within a randomized controlled trial of foster care compared to continued care as usual, indicate that the serotonin transporter linked polymorphic region genotype moderates the relation between early caregiving environments to predict externalizing behavior in children exposed to early institutional care in a manner most consistent with differential susceptibility.
In this paper I shall consider Hume's claim that it is in vain to ask “Whether there be body or not ?’ I have often been puzzled by this interesting remark; puzzled as to just what he meant by it, why he said it, and whether he was right. I don't expect to do any more than explore some of the possibilities and suggest some tentative answers in this discussion. Hume seems to have argued that we can't take this question seriously because we could never sincerely believe what we said if we denied that “body” exists; and that we can't have any genuine doubt on this head because “certain trivial qualities of the fancy” (p. 217) lead us inevitably into a “gross illusion” (ibid). We are thus stuck having to believe what we can prove to be false. Reason mocks us like a palsied hand, knocking away precisely what it tries hardest to grasp. This, I say, is what Hume seems to have argued. But let's see what else we can do with his words. I shall begin by giving a brief account of this belief in “body”. I shall then explore some senses in which the question of the existence of body might turn out to be vain.
In the Principles of Philosophy the first positive claim that Descartes makes after he has established his skeptical starting point is not the claim of the cogito. It is, rather, the claim that “we possess a free will.”