First-Order Decoupling Transition in the Vortex Lattice of Bi2Sr2CaCu2O8 from Local Mutual Inductance Measurements

We have used a miniature mutual inductance technique to measure the ac transmittivity of Bi2Sr2CaCu2O8 crystals in small applied dc fields. A sharp change in the inductive voltage in the vicinity of the irreversibility line at fields below 60 mT and temperatures above about 40 K is observed. The effects of ac frequency, dc field, and the orientation of the applied dc field with respect to the c axis are investigated. This sharp feature appears to be similar to the melting transition recently observed in local magnetic measurements. We find it is associated with changes in the c-axis resistivity and is consistent with a first-order decoupling transition

An analysis of the spanish ceramic tile industry research contracts and patents

In this work, we apply a systemic approach to the analysis of a particular geographic territory, the industrial district. We are particularly interested in analysing the interaction between the productive-technological environment and the scientific environment by an examination of research contracts and patents. Our analysis shows that R&D activity in the Spanish ceramic tile District Innovation System was mainly conducted by suppliers. Final producers’ innovation efforts were related to non-technological aspects and differentiatio

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

Towards real-time 4D radiation dosimetry on an MRI-Linac

4D radiation dosimetry using a highly radiation-sensitive polymer gel dosimeter with real-time quantitative magnetic resonance imaging (MRI) readout is presented as a technique to acquire the accumulated radiation dose distribution during image-guided radiotherapy on an MRI-Linac. Optimized T 2-weighted Turbo-Spin-Echo (TSE) scans are converted into quantitative ΔR 2 maps and subsequently to radiation dose maps. The concept of temporal uncertainty is introduced as a metric of effective temporal resolution. A mathematical framework is presented to optimize the echo time of the TSE sequence in terms of dose resolution, and the trade-off between temporal resolution and dose resolution is discussed. The current temporal uncertainty achieved with the MAGAT gel dosimeter on a 1 T MRI-Linac is 3.8 s which is an order of magnitude better than what has been achieved until now. The potential of real-time 4D radiation dosimetry in a theragnostic MRI-Linac is demonstrated for two scenarios: an irradiation with three coplanar beams on a head phantom and a dynamic arc treatment on a cylindrical gel phantom using a rotating couch. The dose maps acquired on the MRI-Linac are compared with a treatment plan and with dose maps acquired on a clinical 3 T MRI scanner. 3D gamma map evaluations for the different modalities are provided. While the presented method demonstrates the potential of gel dosimetry for tracking the dose delivery during radiotherapy in 4D, a shortcoming of the MAGAT gel dosimeter is a retarded dose response. The effect of non-ideal radiofrequency pulses resulting from limitations in the specific absorption rate or B1-field inhomogeneity on the TSE acquired ΔR 2 values is analysed experimentally and by use of computational modelling with a Bloch simulator

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy.

A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T1-weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water:fat peak area ratios and water T2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water:fat ratios and water T2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water:fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment

Selection of diagnostic features on breast MRI to differentiate between malignant and benign lesions using computer-aided diagnosis: differences in lesions presenting as mass and non-mass-like enhancement

Purpose: To investigate methods developed for the characterisation of the morphology and enhancement kinetic features of both mass and non-mass lesions, and to determine their diagnostic performance to differentiate between malignant and benign lesions that present as mass versus non-mass types. Methods: Quantitative analysis of morphological features and enhancement kinetic parameters of breast lesions were used to differentiate among four groups of lesions: 88 malignant (43 mass, 45 non-mass) and 28 benign (19 mass, 9 non-mass). The enhancement kinetics was measured and analysed to obtain transfer constant (Ktrans) and rate constant (kep). For each mass eight shape/margin parameters and 10 enhancement texture features were obtained. For the lesions presenting as nonmass-like enhancement, only the texture parameters were obtained. An artificial neural network (ANN) was used to build the diagnostic model. Results: For lesions presenting as mass, the four selected morphological features could reach an area under the ROC curve (AUC) of 0.87 in differentiating between malignant and benign lesions. The kinetic parameter (kep) analysed from the hot spot of the tumour reached a comparable AUC of 0.88. The combined morphological and kinetic features improved the AUC to 0.93, with a sensitivity of 0.97 and a specificity of 0.80. For lesions presenting as non-mass-like enhancement, four texture features were selected by the ANN and achieved an AUC of 0.76. The kinetic parameter kepfrom the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. Conclusion: The results suggest that the quantitative diagnostic features can be used for developing automated breast CAD (computer-aided diagnosis) for mass lesions to achieve a high diagnostic performance, but more advanced algorithms are needed for diagnosis of lesions presenting as non-mass-like enhancement. © The Author(s) 2009

Ageing, adipose tissue, fatty acids and inflammation

A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults