Experimental investigation of inter-element isolation in a medical array transducer at various manufacturing stages

This work presents the experimental investigation of vibration maps of a linear array transducer with 192 piezoelements by means of a laser Doppler vibrometer at various manufacturing finishing steps in air and in water. Over the years, many researchers have investigated cross-coupling in fabricated prototypes but not in arrays at various manufacturing stages. Only the central element of the array was driven at its working frequency of 5 MHz. The experimental results showed that the contributions of cross-coupling depend on the elements of the acoustic stack: Lead Zirconate Titanate (PZT), kerf, filler, matching layer, and lens. The oscillation amplitudes spanned from (6 ± 38%) nm to (110 ± 40%) nm when the energized element was tested in air and from (6 ± 57%) nm to (80 ± 67%) nm when measurements were obtained under water. The best inter-element isolation of -22 dB was measured in air after cutting the kerfs, whereas the poorest isolation was -2 dB under water with an acoustic lens (complete acoustic stack). The vibration pattern in water showed a higher standard deviation on the displacement measurements than the one obtained in air, due to the influence of acousto-optic interactions. The amount increased to 30% in water, as estimated by a comparison with the measurements in air. This work describes a valuable method for manufacturers to investigate the correspondence between the manufacturing process and the quantitative evaluations of the resulting effects

Water uptake and swelling in single trabeculæ from human femur head.

The swelling of air-dried single trabeculae from human femur heads was obtained by complete immersion in water and the dimensional changes of the samples were measured over time. The experimental results were analyzed under the viewpoint of the diffusion through a porous material. The dimensional changes of the single trabeculae were 0.26 ± 0.15 percent (length), 0.45 ± 0.25 percent (width) and 1.86 ± 0.97 percent (thickness). The diffusion coefficients were then calculated from the swelling recorded over time and a value of (4.12 ± 0.8) x 10(-10)(m (2)s(-1)) (mean ± standard deviation) was found.   Since the dimensional variations of the specimens is due to the swelling of the collagen bone matrix, this technique could offer new insights for (1) a selective characterization of bone microstructure at the collagen matrix level and (2) the dynamics of diffusion through bone tissue

Analysis of tissue surrounding thyroid nodules by ultrasound digital images

Since US is not easily reproducible, the digital image analysis (IA) has been proposed so that the image evaluation is not subjective. In fact, IA meets the criteria of objectivity, accurateness, and reproducibility by a matrix of pixels whose value is displayed in a gray level. This study aims at evaluating via IA the tissue surrounding a thyroid nodule (backyard tissue, BT) from goitres with benign (b-BT) and malignant (m-BT) lesions. Sixty-nine US images of thyroid nodules surrounded by adequate thyroid tissue was classified as normoechoic and homogeneous were enrolled as study group. Forty-three US images from normal thyroid (NT) glands were included as controls. Digital images of 800 × 652 pixels were acquired at a resolution of eight bits with a 256 gray levels depth. By one-way ANOVA, the 43 NT glands were not statistically different (P = 0.91). Mean gray level of normal glands was significantly higher than b-BT (P = 0.026), and m-BT (P = 0.0001), while no difference was found between b-BT and m-BT (P = 0.321). NT tissue boundary external to the nodule was found at 6.0 ± 0.5 mm in cancers and 4.0 ± 0.5 mm in benignancies (P = 0.001). These data should indicate that the tissue surrounding a thyroid nodule may be damaged even when assessed as normal by US. This is of interest to investigate the extranodular effects of thyroid tumors

Binding properties of different categories of IDO1 inhibitors: a microscale thermophoresis study

Aim: Inhibition of IDO1 is a strategy pursued in the immune-oncology pipeline for the development of novel anticancer therapies. At odds with an ever-increasing number of inhibitors being disclosed in the literature and patent applications, only very few compounds have hitherto advanced in clinical settings. Materials & methods: We have used MicroScale Thermophoresis analysis and docking calculations to assess on a quantitative basis the binding properties of distinct categories of inhibitors to IDO1. Results: Results shed further light on hidden molecular aspects governing the recognition by the enzyme of compounds with different mechanism of inhibition. Conclusion: Results pinpoint specific binding features of distinct inhibitors to IDO1 that offer clues for the design of next-generation inhibitors of the enzyme

Hyperthermic superparamagnetic nanoparticles modulate adipocyte metabolism

Adipocytes are the principal cellular component in adipose tissue and their excessive hyperplasia or hypertrophy is actively involved in regulating physiologic and pathologic processes such as inflammation, cardiovascular disease, obesity and tumour. The main depot of energy in adipocytes is represented by lipid droplets, intracellular organelles that play fundamental roles in regulation of metabolic processes. An accumulation of such droplets could be a potential biomarker of disease caused by metabolic dysregulation. Recent studies have demonstrated that heat shock is associated with alteration in energy metabolism: the aim of this study is to modulate the energy metabolism of the adipocytes via controlled administration of thermal energy to reduce the number of lipid droplets. We have investigated the effect of controlled heating of adipocytes using an alternating magnetic field (AMF) on samples loaded with superparamagnetic nanoparticles (MNP) as heating agent

Good practices for the development of budget impact models at regional level

Introduction: The present work aims to discuss the current scenario of procedures and regulations regarding budget impact analysis/models (BIA/BIM) at regional level in Italy and to provide a standardized approach and detailed recommendations for developing these analyses. Method: A systematic review of the literature was conducted in order to collect existing guidelines or specific regional procedures for budget impact analysis in Italy. All the records were analysed in qualitative terms according to a pre-specified analytical framework, based on the ISPOR BIA guidelines. At the end of the analysis, a consensus questionnaire was developed to establish agreed approaches and to provide possible solutions to any critical issues. A list of 39 statements was developed. The survey was distributed to 69 experts who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement. Results: Sisty-nine experts answered the questionnaire; a total of 30/39 statements achieved consensus. There was agreement on most of the statements. Time horizon to consider and costs were the issues on which no agreement was found. The results allowed the working group to define a list of good practices. Conclusion: While the structure and development of BIM are now well-known and well-applied at national level, there remains a great diversity of management of BIM tools at regional level. Consensus was reached among participating experts, as to the main characteristics, determinants and features of regional BIA/BIM in the perspective of the Italian payer

Harnessing the reverse cholesterol transport pathway to favor differentiation of monocyte-derived APCs and antitumor responses

Lipid and cholesterol metabolism play a crucial role in tumor cell behavior and in shaping the tumor microenvironment. In particular, enzymatic and non-enzymatic cholesterol metabolism, and derived metabolites control dendritic cell (DC) functions, ultimately impacting tumor antigen presentation within and outside the tumor mass, dampening tumor immunity and immunotherapeutic attempts. The mechanisms accounting for such events remain largely to be defined. Here we perturbed (oxy)sterol metabolism genetically and pharmacologically and analyzed the tumor lipidome landscape in relation to the tumor-infiltrating immune cells. We report that perturbing the lipidome of tumor microenvironment by the expression of sulfotransferase 2B1b crucial in cholesterol and oxysterol sulfate synthesis, favored intratumoral representation of monocyte-derived antigen-presenting cells, including monocyte-DCs. We also found that treating mice with a newly developed antagonist of the oxysterol receptors Liver X Receptors (LXRs), promoted intratumoral monocyte-DC differentiation, delayed tumor growth and synergized with anti-PD-1 immunotherapy and adoptive T cell therapy. Of note, looking at LXR/cholesterol gene signature in melanoma patients treated with anti-PD-1-based immunotherapy predicted diverse clinical outcomes. Indeed, patients whose tumors were poorly infiltrated by monocytes/macrophages expressing LXR target genes showed improved survival over the course of therapy. Thus, our data support a role for (oxy)sterol metabolism in shaping monocyte-to-DC differentiation, and in tumor antigen presentation critical for responsiveness to immunotherapy. The identification of a new LXR antagonist opens new treatment avenues for cancer patients

U-CHANGE Project: a multidimensional consensus on how clinicians, patients and caregivers may approach together the new urothelial cancer scenario

IntroductionAdvanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations (“as is” scenario) and recommend future actions (“to be” scenario).MethodsTwenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts.ResultsRecommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies.DiscussionWhile the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease

Evidence of entropic elasticity of human bone trabeculae at low strains

We performed 60 microtensile tests on 6 single trabeculae excised from a human femur head at various maximum tensile loads. The obtained results show a clear dependence of the calculated stress-strain behaviour from the applied load and thus from the mean stress over the cross section of the trabecula. The pooled data were found in good agreement with a combination of both the model of the nonlinear stress-strain behaviour of collagen fibrils and that for the modulus of elasticity of staggered mineralized collagen. This circumstance could also suggest a realistic explanation of the extreme variability found in literature for the elastic modulus of the trabecular material. In particular, when the trabeculae are solicited with relatively low stresses, their mechanical properties are mainly affected by the entropic elasticity of collagen molecules. This work offers both experimental data and a reasonable interpretation of the behaviour of fully mineralized tissue at low strains, that is up to about 0.1%. (C) 2010 Elsevier Ltd. All rights reserved