457 research outputs found

    Cost-effective intervention thresholds against osteoporotic fractures based on FRAX® in Switzerland

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    Summary: FRAX-based cost-effective intervention thresholds in the Swiss setting were determined. Assuming a willingness to pay at 2× Gross Domestic Product per capita, an intervention aimed at reducing fracture risk in women and men with a 10-year probability for a major osteoporotic fracture at or above 15% is cost-effective. Introduction: The fracture risk assessment algorithm FRAX® has been recently calibrated for Switzerland. The aim of the present analysis was to determine FRAX-based fracture probabilities at which intervention becomes cost-effective. Methods: A previously developed and validated state transition Markov cohort model was populated with Swiss epidemiological and cost input parameters. Cost-effective FRAX-based intervention thresholds (cost-effectiveness approach) and the cost-effectiveness of intervention with alendronate (original molecule) in subjects with a FRAX-based fracture risk equivalent to that of a woman with a prior fragility fracture and no other risk factor (translational approach) were calculated based on the Swiss FRAX model and assuming a willingness to pay of 2 times Gross Domestic Product per capita for one Quality-adjusted Life-Year. Results: In Swiss women and men aged 50years and older, drug intervention aimed at decreasing fracture risk was cost-effective with a 10-year probability for a major osteoporotic fracture at or above 13.8% (range 10.8% to 15.0%) and 15.1% (range 9.9% to 19.9%), respectively. Age-dependent variations around these mean values were modest. Using the translational approach, treatment was cost-effective or cost-saving after the age 60years in women and 55 in men who had previously sustained a fragility fracture. Using the latter approach leads to considerable underuse of the current potential for cost-effective interventions against fractures. Conclusions: Using a FRAX-based intervention threshold of 15% for both women and men should permit cost-effective access to therapy to patients at high fracture probability based on clinical risk factors and thereby contribute to further reduce the growing burden of osteoporotic fractures in Switzerlan

    Tunable few electron quantum dots in InAs nanowires

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    Quantum dots realized in InAs are versatile systems to study the effect of spin-orbit interaction on the spin coherence, as well as the possibility to manipulate single spins using an electric field. We present transport measurements on quantum dots realized in InAs nanowires. Lithographically defined top-gates are used to locally deplete the nanowire and to form tunneling barriers. By using three gates, we can form either single quantum dots, or two quantum dots in series along the nanowire. Measurements of the stability diagrams for both cases show that this method is suitable for producing high quality quantum dots in InAs.Comment: 8 pages, 4 figure

    Potential of a cyclone prototype spacer to improve in vitro dry powder delivery

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    Copyright The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedPurpose: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrierbased DPIs was investigated. Methods: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30-60 Lmin-1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Results: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51 % at 30 Lmin-1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. Conclusion: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.Peer reviewe

    Twinning superlattices in indium phosphide nanowires

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    Here, we show that we control the crystal structure of indium phosphide (InP) nanowires by impurity dopants. We have found that zinc decreases the activation barrier for 2D nucleation growth of zinc-blende InP and therefore promotes the InP nanowires to crystallise in the zinc blende, instead of the commonly found wurtzite crystal structure. More importantly, we demonstrate that we can, by controlling the crystal structure, induce twinning superlattices with long-range order in InP nanowires. We can tune the spacing of the superlattices by the wire diameter and the zinc concentration and present a model based on the cross-sectional shape of the zinc-blende InP nanowires to quantitatively explain the formation of the periodic twinning.Comment: 18 pages, 4 figure

    High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age of patients with "classic" high hyperdiploidy was lower than that of patients with translocation-positive high hyperdiploidy (P53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by a particularly favorable outcome.Swedish Childhood Cancer Foundation Swedish Cancer Society Swedish Research Counci

    Harm–benefit analysis – what is the added value?:A review of alternative strategies for weighing harms and benefits as part of the assessment of animal research

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    Animal experiments are widely required to comply with the 3Rs, to minimise harm to the animals and to serve certain purposes in order to be ethically acceptable. Recently, however, there has been a drift towards adding a so-called harm-benefit analysis as an additional requirement in assessing experiments. According to this, an experiment should only be allowed if there is a positive balance when the expected harm is weighed against the expected benefits. This paper aims to assess the added value of this requirement. Two models, the discourse model and the metric model, are presented. According to the former, the weighing of harms and benefits must be conducted by a committee in which different stakeholders engage in a dialogue. Research into how this works in practice, however, shows that in the absence of an explicit and clearly defined methodology, there are issues about transparency, consistency and fairness. According to the metric model, on the other hand, several dimensions of harms and benefits are defined beforehand and integrated in an explicit weighing scheme. This model, however, has the problem that it makes no real room for ethical deliberation of the sort committees undertake, and it has therefore been criticised for being too technocratic. Also, it is unclear who is to be held accountable for built-in ethical assumptions. Ultimately, we argue that the two models are not mutually exclusive and may be combined to make the most of their advantages while reducing the disadvantages of how harm-benefit analysis in typically undertaken

    Seeing as sensing : the structuring of bodily experience in modern pictorial art

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    Two main arguments are developed in this thesis: first is the claim that our ability to make and understand representational pictures has a natural basis in our capacity to see. In this respect, I have drawn on the ideas of the visual scientist, David Marr and on the theory of representation expounded by John Willats. Second, I argue that the view articulated by these theorists forms a theoretical backdrop for, but does not satisfactorily explain, how pictures may heighten our sense of bodily presence. A central aim of this thesis is therefore to show how this mode of expression is also non-arbitrarily linked to the process of seeing by virtue of its relationship with our visuomotor capacities. In order to give substance to these ideas, I have attempted to weave together knowledge of art history with neuropsychological evidence and phenomenological philosophy. In applying this view to the work of particular artists, I have largely focussed on the oeuvre of Cézanne and the Cubists. However, the general form of this argument is intended to have wider implications, indicating the development of a stylistic tendency in modern art and showing how it differs from that of the Renaissance tradition. In conclusion, my thesis expresses the view that vision – and hence representation – can be divided along two separate lines: one related to a conceptual form of seeing and the other related to a bodily form of perception. The "crisis of representation" in the late nineteenth century is therefore considered indicative of a rejection of the former mode of visuality. Instead, modern artists are said to re-structure the viewing experience so that it shows the reliance of sight on the body, thus permitting the beholder a more active and constitutive role in the perception of art.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Fragility fractures in Europe : burden, management and opportunities

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    Summary This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years. Introduction Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6). Methods A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric. Results Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 individuals age 50 years or more were estimated at 21 years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible individuals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men; an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided. Conclusions Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are appropriately assessed and treated
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