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The Institute of Health Economics offers a suite of analyses that provide developers an understanding of the expected commercial viability of an early stage health technology. In combination, these analyses form the Value-Engineered Translation framework. These methods incorporate innovative methods to manage uncertainty in early economic evaluations, in particular, moving beyond current stochastic assessments of headroom to account for inter-market variability in value hurdles, as well as incorporating social value premia considerations. An illustration of these methods is demonstrated using the example of a non-invasive diagnostic test (called DCRSHP) at an early stage of development, compared to current practice of cystoscopy in the diagnosis of bladder cancer.
Competing technologies were identified to inform the headroom assessment based on price and effectiveness. Then, a model-based cost-effectiveness analysis was undertaken incorporating headroom analysis, stochastic one-way sensitivity analysis, and value of information analysis using data from secondary sources.
Currently there are a number of non-invasive tests available, but none have sufficient test accuracy to be suitable for bladder cancer diagnosis alone. From the headroom analysis, DCRSHP can be priced at up to CAD 790 (i.e. USD 588) and still be cost-effective compared to the current practice of cystoscopy. Interestingly this price can be increased for patient groups that have lower levels of bladder cancer prevalence.
The requirements of economic evaluations depend on the stage of technology development, and analysis approaches must reflect this. The results here indicate that DCRSHP clears the value hurdle in terms of being cost-effective, and thus provides the opportunity to make a commercial return on future investment. Future analysis of DCRSHP could consider the cost drivers for development of the technology, including the regulatory pathways, costs associated with the intellectual asset management for the technology, and alternative manufacturing costs. All of which contribute to the research-to-practice continuum.
Inspired by impossibility theorems of social choice theory, many democratic theorists have argued that aggregative forms of democracy cannot lend full democratic justification for the collective decisions reached. Hence, democratic theorists have turned their attention to deliberative democracy, according to which “outcomes are democratically legitimate if and only if they could be the object of a free and reasoned agreement among equals” (Cohen 1997a, 73). However, relatively little work has been done to offer a formal theory of democratic deliberation. This article helps fill that gap by offering a formal theory of three different modes of democratic deliberation: myopic discussion, constructive discussion, and debate. We show that myopic discussion suffers from indeterminacy of long run outcomes, while constructive discussion and debate are conclusive. Finally, unlike the other two modes of deliberation, debate is path independent and converges to a unique compromise position, irrespective of the initial status quo.
There is limited empirical information on service-level outcome domains and indicators for the large number of people with intellectual disabilities being treated in forensic psychiatric hospitals.
This study identified and developed the domains that should be used to measure treatment outcomes for this population.
A systematic review of the literature highlighted 60 studies which met eligibility criteria; they were synthesised using content analysis. The findings were refined within a consultation and consensus exercises with carers, patients and experts.
The final framework encompassed three a priori superordinate domains: (a) effectiveness, (b) patient safety and (c) patient and carer experience. Within each of these, further sub-domains emerged from our systematic review and consultation exercises. These included severity of clinical symptoms, offending behaviours, reactive and restrictive interventions, quality of life and patient satisfaction.
To index recovery, services need to measure treatment outcomes using this framework.
The hybrid procedure is one mode of initial palliation for hypoplastic left heart syndrome. Subsequently, patients proceed with either the “three-stage” pathway – comprehensive second stage followed by Fontan completion – or the “four-stage” pathway – Norwood procedure, hemi-Fontan, or Fontan completion. In this study, we describe somatic growth patterns observed in the hybrid groups and a comparison primary Norwood group.
A retrospective analysis of patients who have undergone hybrid procedure and Fontan completion was performed. Weight-for-age and height-for-age z-scores were recorded at each operation.
We identified 13 hybrid patients – eight in the three-stage pathway and five in the four-stage pathway – and 49 Norwood patients. Weight: three stage: weight decreased from hybrid procedure to comprehensive second stage (−0.4±1.3 versus −2.3±1.4, p<0.01) and then increased to Fontan completion (−0.4±1.5 versus −0.6±1.4, p<0.01); four stage: weight decreased from hybrid procedure to Norwood (−2.0±1.4 versus −3.3±0.9, p=0.06), then stabilised to hemi-Fontan. Weight increased from hemi-Fontan to Fontan completion (−2.7±0.6 versus −1.0±0.7, p=0.01); primary Norwood group: weight decreased from Norwood to hemi-Fontan (p<0.001) and then increased to Fontan completion (p<0.001). Height: height declined from hybrid procedure to Fontan completion in the three-stage group. In the four-stage group, height decreased from hybrid to hemi-Fontan, and then increased to Fontan completion. The Norwood group decreased in height from Norwood to hemi-Fontan, followed by an increase to Fontan completion.
In this study, we show that patients undergoing the hybrid procedure have poor weight gain before superior cavopulmonary connection, before returning to baseline by Fontan completion. This study identifies key periods to target poor somatic growth, a risk factor of morbidity and worse neurodevelopmental outcomes.
We describe a system for rapidly screening hundreds of nanoparticle samples using transmission electron microscopy (TEM). The system uses a liquid handling robot to place up to 96 individual samples onto a single standard TEM grid at separate locations. The grid is then transferred into the TEM and automated software is used to acquire multiscale images of each sample. The images are then analyzed to extract metrics on the size, shape, and morphology of the nanoparticles. The system has been used to characterize plasmonically active nanomaterials.
This article establishes a folk theorem for a model of repeated elections with adverse selection: when citizens (voters and politicians) are sufficiently patient, arbitrary policy paths through arbitrarily large regions of the policy space can be supported by a refinement of perfect Bayesian equilibrium. Politicians are policy motivated (so office benefits cannot be used to incentivize policy choices), the policy space is one-dimensional (limiting the dimensionality of the set of utility imputations), and politicians’ preferences are private information (so punishments cannot be targeted to a specific type). The equilibrium construction relies critically on differentiability and strict concavity of citizens’ utility functions. An extension of the arguments allows policy paths to depend on the office holder's type, subject to incentive compatibility constraints.
Electoral platform convergence is perceived unfavorably by both the popular press and many academic scholars. Arguably, to paraphrase, “it does not provide enough choice” between candidates. This article provides a formal account of the perceived negative effects of platform convergence. We show that when parties do not know voters' preferences precisely, all voters ex ante prefer some platform divergence to convergence at the ex ante median. After characterizing the unique symmetric equilibrium of competition between responsible (policy-motivated) parties, we conclude that all voters ex ante prefer responsible parties to opportunistic (purely office-motivated) ones when parties are sufficiently ideologically polarized that platforms diverge, but not so polarized that they diverge excessively. However, greater polarization increases the scope for office benefits as an instrument for institutional design. We calculate the socially optimal level of platform divergence and show that office benefits can be used to achieve this first-best outcome, if parties are sufficiently ideologically polarized.
Assessing those with personality disorder for treatment in secure settings is known to be unsatisfactory.
To examine the utility of a standardised assessment of offenders with personality disorder referred for treatment in secure care in a naturalistic study.
A consecutive series of 89 men were assessed with a battery of four recommended instruments measuring personality and risk. Decisions on whether or not to admit were based on a multidisciplinary discussion informed by these assessments.
Of the 89 comprehensively assessed referrals, 60 (67%) were offered admission. High scores on the Psychopathy Checklist–Revised (especially on Factor 1) was the only measure that was associated with rejection. Of 44 patients discharged, 29 (66%) failed to complete treatment; none of the pre-admission assessments distinguished ‘completers' from ‘non-completers'. Although skills were acquired on the unit, follow-up of 24 men in the community showed that this had only a marginal effect on re-offending rate (58%).
Current recommended assessment methods appear unsatisfactory in identifying those who either (a) complete treatment or (b) benefit from treatment. Our results throw doubt on their value.
Previous studies of borderline personality disorder report neuropsychological impairments in several domains, including memory. No studies have compared memory functioning in high-risk prisoners with borderline personality disorder with similar prisoners with other personality disorders.
To explore mnemonic impairments in prisoners undergoing personality assessment as part of the dangerous and severe personality disorder initiative or detained in a medium secure facility.
We investigated memory function in 18 prisoners with borderline personality disorder and 18 prisoners with other personality disorders.
Prisoners with borderline personality disorder exhibited a pattern of multi-modal impairments in the immediate and delayed recall of verbal and visual information, with some association with affective instability. These deficits were not associated with the severity of personality disturbance.
These data suggest that memory deficits have some specificity in relation to the constituent traits of borderline personality disorder and indicate that neuropsychological assessment may be a source of useful adjunctive information for distinguishing between the cognitive and psychological difficulties of individual prisoners.
Objectives: Agraphia is the loss or impairment of the ability to produce written language as a consequence of brain damage and is a well recognised feature of dementia. However there is no generally accepted classification of agraphic disorders. Our aim was to determine the influence of writing style, lettercase and sentence polarity of the writing component of Folstein's MMSE on the overall test score.
Methods: We retrospectively reviewed the ‘write a sentence’ request of Folstein's MMSE of 280 randomly selected patients attending a geriatric day hospital. We analysed four sentence characteristics: 1 Number of words, 2 Writing legibility, 3 Sentence polarity, 4 Letter case.
Results: 280 MMSE forms were examined, 165 were from female patients. Mean age was 81.7(± 6.6) years. Mean MMSE score was 21.6 (males: 21.9, females: 21.4). Significant correlation was detected between the overall MMSE score and both legibility and number of words. Legibility scores were significantly higher for females than for males (7.2 vs. 6.6, p < 0.03). The mean MMSE of females writing in lowercase was significantly higher than for those writing in uppercase (21.5 vs. 18.6, p < 0.05). The mean MMSE score of subjects writing sentences with a positive tone was significantly higher than that of those writing a neutral or negative sentence (22.6 vs. 21.0 p < 0.03).
Conclusions: We have demonstrated a relationship between the content and structure of the writing assessment aspect of the MMSE and the overall test score.
The polymerase chain reaction (PCR) technique was used to investigate the fate of a transgene in the rumen of sheep fed silage and maize grains from an insect-resistant maize line. A 1914-bp DNA fragment containing the entire coding region of the synthetic cryIA(b) gene was still amplifiable from rumen fluid sampled 5 h after feeding maize grains. The same target sequence, however, could not be amplified from rumen fluid sampled from sheep fed silage prepared from the genetically modified maize line. PCR amplification of a shorter (211-bp), yet still highly specific, target sequence was possible with rumen fluid sampled up to 3 and 24 h after feeding silage and maize grains, respectively. These findings indicate that intact transgenes from silage are unlikely to survive significantly in the rumen since a DNA sequence 211-bp long is very unlikely to transmit genetic information. By contrast, DNA in maize grains persists for a significant time and may, therefore, provide a source of transforming DNA in the rumen. In addition, we have examined the biological activity of plasmid DNA that had previously been exposed to the ovine oral cavity. Plasmid extracted from saliva sampled after incubation for 8 min was still capable of transforming competent Escherichia coli to kanamycin resistance, implying that DNA released from the diet within the mouth may retain sufficient biological activity for the transformation of competent oral bacteria.
Type classes are a novel combination of parametric polymorphism and constrained types.
Although most implementations restrict type classes to be single-parameter, the generalization
to multi-parameter type classes has gained increasing attention. A problem with multi-parameter
type classes is the increased possibilities they introduce for ambiguity in inferred
types, impacting their usefulness in many practical situations. A new type-checking strategy,
domain-driven unifying resolution, is identified as an approach to solve these problems. Domain-driven
unifying resolution is simple, efficient, and practically useful. However, even with severe
restrictions on instance definitions, it is not possible to guarantee that type-checking with
unifying resolution terminates. This is in contrast with the naive generalization of single
parameter resolution strategies. Domain-driven unifying resolution is guaranteed to terminate
if the type class constraints are satisfiable; however satisfiability is undecidable even with severe
restrictions on instance definitions. These results shed some light on ambiguity problems with
multi-parameter type classes.
We provide a general theory of collective decision making, one that relates social choices to the strategic incentives of individuals, by generalizing the Baron-Ferejohn (1989) model of bargaining to the multidimensional spatial model. We prove existence of stationary equilibria, upper hemicontinuity of equilibrium outcomes in structural and preference parameters, and equivalence of equilibrium outcomes and the core in certain environments, including the one-dimensional case. The model generates equilibrium predictions even when the core is empty, and it yields a “continuous” generalization of the core in some familiar environments in which the core is nonempty. As the description of institutional detail in the model is sparse, it applies to collective choice in relatively unstructured settings and provides a benchmark for the general analysis of legislative and parliamentary politics.
A large number of proteid substances, when in solution, are coagulable by heat. As the temperature of such a fluid is raised, faint opalescence at first appears, and then, at a higher temperature, masses (flocculi) of albumen separate out, in most cases, suddenly, from the fluid. It is generally held that each coagulable albumen is so affected at a definite temperature peculiar to itself; thus, egg albumen is said to become opalescent at 60° C, and to separate out in flocculi at 63° C. Unfortunately, hardly two observers agree as to the exact temperature at which opalescence and coagulation occur; thus, keeping to the example, egg albumen, Wurtz puts the coagulation point at 73° C, and Henrijean at 60° to 61° C.
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