The death of cost-minimization analysis?

Four different types of evaluation methods, cost-benefit analysis (CBA), cost-utility analysis (CUA), cost-effectiveness analysis (CEA) and cost-minimization analysis (CMA), are usually distinguished. In this note, we pronounce the (near) death of CMA by showing the rare circumstances under which CMA is an appropriate method of analysis. We argue that it is inappropriate for separate and sequential hypothesis tests on differences in effects and costs to determine whether incremental cost-effectiveness (or cost-utility) should be estimated. We further argue that the analytic focus should be on the estimation of the joint density of cost and effect differences, the quantification of uncertainty surrounding the incremental cost-effectiveness ratio and the presentation of such data as cost-effectiveness acceptability curves. Two examples from recently published CEA are employed to illustrate the issues. The first shows a situation where analysts might be tempted (inappropriately) to employ CMA rather than CEA. The second illustrates one of the rare circumstances in which CMA may be justified as a legitimate form of analysis

Fasciola hepatica:The therapeutic potential of a worm secretome

The success of helminth parasites is partly related to their ability to modulate host immune responses towards an anti-inflammatory/regulatory phenotype. This ability resides with the molecules contained in the secretome of various helminths that have been shown to interact with host immune cells and influence their function. Consequently, there exists a unique opportunity to exploit these molecules for the prophylactic and therapeutic treatment of human pro- and auto-inflammatory disorders (for example septic shock, transplant rejection and autoimmune disease). In this review, we describe the mechanisms used by the trematode parasite, Fasciola hepatica, to modulate the immune responses of its host and discuss the potent immune-modulatory effects of three individual molecules within the secretome; namely cathepsin L1, peroxiredoxin and helminth defence molecule. With a focus on the requirements from industry, we discuss the strategies by which these molecules may be clinically developed to control human immune responses in a way that is conducive to the prevention of immune-mediated diseases

Cardiorespiratory responses in an Antarctic fish suggest limited capacity for thermal acclimation

Polar fishes are at high risk from increasing seawater temperatures. Characterising the 30 physiological responses to such changes may both clarify mechanisms that permit life 31 under extreme conditions, and identify limitations in the response to continued global 32 warming. We hypothesised that Notothenia coriiceps would show physiological 33 compensation after an acute exposure to 5oC, and following 6wk warm acclimation, 34 compared to ambient temperature (0oC). However, initial tachycardia (22.4±2.8 vs. 35 12.8±1.1min-1; P<0.01) was not reversed by acclimation (21.0±1.9min-1). 36 Hyperventilation (45.5±3.1 vs. 21.4±2.4min-1; P<0.001) showed a modest reduction 37 (38.0±2.9min-1; P<0.05), while resting oxygen consumption (0.52±0.08mmol.kg–1.h– 38 1) was acutely increased at 5oC (1.07±0.10mmol.kg–1.h–1; P<0.001) but unchanged 39 with acclimation. Autonomic blockade showed initial responses were mainly of vagal 40 origin, with little subsequent withdrawal or recovery in long-term heart rate variability 41 after 6wk. Given the limited cardiorespiratory capacity to withstand sustained 42 warming, effective physiological compensation likely requires a more prolonged 43 acclimation period

Shock fronts in the symbiotic system BI Crucis

We investigate the symbiotic star BI Crucis through a comprehensive and self-consistent analysis of the spectra emitted in three different epochs: 60's, 70's, and late 80's. In particular, we would like to find out the physical conditions in the shocked nebula and in the dust shells, as well as their location within the symbiotic system, by exploiting both photometric and spectroscopic data from radio to UV. We suggest a model which, on the basis of optical imaging, emission line ratios and spectral energy distribution profile, is able to account for collision of the winds, formation of lobes and jets by accretion onto the WD, as well as for the interaction of the blast wave from a past, unrecorded outburst with the ISM. We have found that the spectra observed throughout the years show the marks of the different processes at work within BI Cru, perhaps signatures of a post-outburst evolution. We then call for new infrared and millimeter observations, potentially able to resolve the inner structure of the symbiotic nebula.Comment: 13 pages, 9 figures, 2 tables; accepted for publication in MNRA

Rapid automated measurement of body fat distribution from whole-body MRI

The accurate determination of a person’s total body fat is an important issue in medical analysis because obesity is a significant contributing factor to a variety of serious health problems. The medical literature identifies a wide range of diseases that are closely linked to obesity. Current methods of fat assessment are largely inaccurate, and most current methods of fat determination cannot show regional fat distribution, which is important in defining disease risk. We introduce a method that combines computer-aided techniques with whole-body MRI techniques and enables accurate quantification and visualization of total body fat burden and regional fat distribution. This technique may be important in identifying and treating at-risk populations

Short-term emission line and continuum variations in Mrk110

We present results of a variability campaign of Mrk110 performed with the 9.2-m Hobby-Eberly Telescope (HET) at McDonald Observatory. The high S/N spectra cover most of the optical range. They were taken from 1999 November through 2000 May. The average interval between the observations was 7.3 days and the median interval was only 3.0 days. Mrk110 is a narrow-line Seyfert 1 galaxy. During our campaign the continuum flux was in a historically low stage. Considering the delays of the emission lines with respect to the continuum variations we could verify an ionization stratification of the BLR. We derived virial masses of the central black hole from the radial distances of the different emission lines and from their widths. The calculated central masses agree within 20%. Furthermore, we identified optical HeI singlet emission lines emitted in the broad-line region. The observed line fluxes agree with theoretical predictions. We show that a broad wing on the red side of the [OIII]5007 line is caused by the HeI singlet line at 5016A.Comment: 11 pages, 16 figures, A&A Latex. Accepted for publication in A&A Main Journa

Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology

The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for cognition in mild to moderate Alzheimer's disease (A), memantine for moderate to severe Alzheimer's disease (A) and combination therapy (cholinesterase inhibitors and memantine) may be beneficial (B). Drugs should not be stopped just because dementia severity increases (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E, nutritional supplements and $\textit{Ginkgo biloba}$, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (both Parkinson's disease dementia and dementia with Lewy bodies), and memantine may be helpful (A). No drugs are clearly effective in vascular dementia, though cholinesterase inhibitors are beneficial in mixed dementia (B). Early evidence suggests multifactorial interventions may have potential to prevent or delay the onset of dementia (B). Though the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition in those with or at high risk of Alzheimer's disease are in progress. Though results of pivotal studies in early (prodromal/mild) Alzheimer's disease are awaited, results to date in more established (mild to moderate) Alzheimer's disease have been equivocal and no disease modifying agents are either licensed or can be currently recommended for clinical use

Early Jurassic North Atlantic sea-surface temperatures from TEX86 palaeothermometry

Early Jurassic marine palaeotemperatures have been typically quantified by oxygen-isotope palaeothermometry of benthic and nektonic carbonate and phosphatic macrofossils. However, records of Early Jurassic sea-surface temperatures (SSTs) that can be directly compared with General Circulation Model (GCM) simulations of past climates are currently unavailable. The TEX86 SST proxy is based upon the relative abundance of glycerol dialkyl glycerol tetraethers (GDGTs) preserved in organic-carbon-bearing sediments. This proxy has been used extensively on Cretaceous and Cenozoic materials and, in one study, Middle and Upper Jurassic sediments. Here TEX86 is applied, for the first time, to Lower Jurassic (Sinemurian–Pliensbachian) sediments cored at Deep Sea Drilling Project Site 547 in the North Atlantic. The abundance of GDGTs in these sediments is very low, despite biomarker and Rock-Eval data suggesting that thermal maturity is, generally, low. Sea-floor oxygenation and a high input of reworked terrestrially sourced organic matter may explain the low concentrations. For samples from which it was possible to quantify the relative abundance of GDGTs, TEX86 values range from 0.78 to 0.88, equating to SSTs in excess of >28˚C. These temperatures are broadly comparable with new GCM simulations of the Sinemurian and Pliensbachian stages and support the general view of a predominantly warm climate. The new proxy data suggest that, under favourable geological conditions, it is possible to extend the record of TEX86-based SSTs back into the Early Jurassic

On-demand semiconductor single-photon source with near-unity indistinguishability

Single photon sources based on semiconductor quantum dots offer distinct advantages for quantum information, including a scalable solid-state platform, ultrabrightness, and interconnectivity with matter qubits. A key prerequisite for their use in optical quantum computing and solid-state networks is a high level of efficiency and indistinguishability. Pulsed resonance fluorescence (RF) has been anticipated as the optimum condition for the deterministic generation of high-quality photons with vanishing effects of dephasing. Here, we generate pulsed RF single photons on demand from a single, microcavity-embedded quantum dot under s-shell excitation with 3-ps laser pulses. The pi-pulse excited RF photons have less than 0.3% background contributions and a vanishing two-photon emission probability. Non-postselective Hong-Ou-Mandel interference between two successively emitted photons is observed with a visibility of 0.97(2), comparable to trapped atoms and ions. Two single photons are further used to implement a high-fidelity quantum controlled-NOT gate.Comment: 11 pages, 11 figure

Development of the Malocclusion Impact Questionnaire (MIQ) to measure the oral health-related quality of life of young people with malocclusion: part 1 - qualitative inquiry

OBJECTIVES: To seek the views of adolescents with malocclusion about how the appearance and arrangement of their teeth affects their everyday life and to incorporate these views into a new Malocclusion Impact Questionnaire (MIQ). METHODS: Semi-structured interviews were undertaken with a purposive sample of 30 young people (10-16 years) referred for orthodontic treatment to two dental teaching hospitals. The interviews were recorded, transcribed and analysed using framework analysis. Several themes and sub themes were identified and these were used to identify items to include in the new measure. RESULTS: Three themes emerged which were: concerns about the appearance of their teeth, effect on social interactions and oral health/function. Participants expressed the view that their teeth did not look normal, causing them embarrassment and a lack of confidence, particularly when they were with their peers or having their photograph taken. Concerns regarding the potential effect of a malocclusion on oral health, in terms of food becoming stuck between crooked teeth, interferences when chewing and increased risk of damaging the teeth were also identified. The themes were used to generate individual items for inclusion in the questionnaire. CONCLUSIONS: Common themes relating to the impact of malocclusion on the lives of young people were identified and generated items for the new MIQ to measure the oral health-related quality of life of young people with malocclusion. Part 2 outlines the further development and testing of the MIQ