Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Complex biological pathways including angiogenesis, invasion, osteoclastic activation and bone matrix degradation are involved in the formation of bone metastasis (BM). The aim of our study was to investigate the cross-sectional and longitudinal associations of a panel of 12 serum biochemical markers reflecting biological pathways underlying BM development. In a cross-sectional study, we investigated 29 patients with primary breast carcinoma without BM (BC/BM−), 28 patients with breast carcinoma and BM (BC/BM+) and 15 healthy women. In longitudinal analyses, we investigated 34 patients for whom serum was obtained a two different time points: at the time of primary BC diagnosis and after a median time of 3 years. During this follow-up, 15 patients developed BM, whereas the other 19 remained free of BM. In patients who developed BM, the second samples were obtained before BM was documented by bone scan. The cross-sectional analyses have shown all biochemical markers to be significantly elevated in patients with BM, when compared to the patients without BM and healthy controls, except TGFβ1 that was significantly decreased. Multivariable analyses showed that only the bone resorption markers TRACP 5b, CTX and ICTP, and the marker of angiogenesis VEGF were independently associated with BM. Those markers correctly distinguished 85% of BC patients with or without BM from normal individuals. Longitudinal analyses showed that patients with primary BC who developed BM during follow-up had higher levels of TRACP5b (+95%, P=0.08) at the time of primary diagnosis, those patients had also a higher increases of ICTP (P=0.006), MMP-7 (P=0.004) and TIMP-1 (P=0.017) during follow-up than patients who did not progress toward bone metastasis. This study provides evidence of increase and interrelationship of circulating markers of angiogenesis, invasion and bone resorption in patients with BC with and without BM. Markers of bone resorption have the highest independent diagnostic value for detecting and potentially predicting BM in breast carcinoma patients

The research gap in chronic paediatric pain: A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases

Dielectric and Thermal Properties of Parylene D at High Temperature: Thermal Instability

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Morphology-induced percolation in crosslinked AMPS/Fluorolink for fuel cell membrane application

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Impact of the SG phase morphology on the performances and durability of hybrid polymer membranes for fuel cell applications

International audienceProton-Exchange Membrane Fuel Cells (PEMFC) has emerged as a promising emission-free energy conversion device. However, the ionomer membrane at the heart of the device fails to deliver durable performance (to be achieved: 8000h for transportation, 50000h for stationary) at high temperature (100-150°C vs 80°C for std. Nafion) and low relative humidity (30%RH). The aim of our work is to improve existing membranes (better chemical and thermomechanical stabilities, better conductivities) by Sol-Gel (SG) hybridization. SG precursors are selected to diffuse through commercial membranes and introduce stabilizing organo-functional groups offering either a sacrificial stabilization (consumed over time) or a redox stabilization (regenerable) by degrading oxidizing agents produced during Fuel Cell operation. As the morphology (size, interaction/dispersion, connectivity) and localization (polar/apolar regions) of the SG phase inside the host matrix are parameters expected to be crucial for properties (H+ conductivity, water uptake), durability (H2O2-accelerated aging tests to assess the effectiveness of the reactive SG phase) and performances (FC operation) of the hybrid membranes, we explored their morphology at all relevant length scales. In this purpose, we use a combination of direct space (AFM/SEM/TEM) and reciprocal space (contrast variation SANS/SAXS) techniques (dimensional scale covered: from a hundred to a few nanometers) with regard to the chemistry of the SG Precursors (SGPs) (stabilization group, number of hydrolysable functions), yielding a variety of morphology (mass fractal structure vs. dispersed spherical aggregates vs. interconnected ones). H2O2-accelerated aging tests and preliminary fuel cell tests show promising operability of the hybrid membranes and the potential of the SG phase to inhibit the chemical ageing of sPEEK. With this work, we are confident to reach a predictive approach of the key parameters governing the final properties