Accelerated hermeticity testing of biocompatible moisture barriers used for encapsulation of implantable medical devices

Acceleration protocol plays an important role on barriers reliability evaluation for encapsulation of long-term implantable medical devices. Typically, acceleration is realized by performing tests at elevated temperature: the higher the selected temperature, the higher the acceleration factor. Nevertheless, at high temperatures, reaction mechanisms might be different, resulting in false acceleration test results. Our standard barrier performance test is based on the evaluation of corrosion of copper patterns (resistivity check, Electroscopic Impedance Spectroscopy (EIS), microscopic inspection). The temperature window for accelerated testing has been investigated for our standard barrier tests. The copper patterns, protected by a barrier layer under test, are immersed in PBS (Phosphate Buffered Saline) at temperatures up to 95°C. As barriers the following material/multilayers are selected: (1) Al2O3 ALD, (2) stacked HfO2/Al2O3/HfO2 ALD (further called ALD-3), (3) polyimide, and (4) polyimide/ALD-3/polyimide. In this presentation, the results of the test protocol evaluation will be presented. As expected, the maximum applicable test temperature is dependent on the barrier under test. Furthermore, during the fine-tuning of the accelerated test protocol, we observed for some barriers a clear influence of the shape of the Cu test patterns on the barrier performance. This can be related with processing effects when fabricating the barrier on the copper patterns. This finding stresses the determination of relevant copper patterns -or test structures in general- in order to predict the barrier performance correct for each individual application

RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease

Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted

Contemporary European practice in transcatheter aortic valve implantation: results from the 2022 European TAVI Pathway Registry

BackgroundA steep rise in the use of transcatheter aortic valve implantation (TAVI) for the management of symptomatic severe aortic stenosis occurred. Minimalist TAVI procedures and streamlined patient pathways within experienced Heart Valve Centres are designed to overcome the challenges of ever-increasing procedural volume.AimsThe 2022 European TAVI Pathway Survey aims to describe contemporary TAVI practice across Europe.Materials and methodsBetween October and December 2022, TAVI operators from 32 European countries were invited to complete an online questionnaire regarding their current practice.ResultsResponses were available from 147 TAVI centres in 26 countries. In 2021, the participating centres performed a total number of 27,223 TAVI procedures, with a mean of 185 TAVI cases per centre (median 138; IQR 77–194). Treatment strategies are usually (87%) discussed at a dedicated Heart Team meeting. Transfemoral TAVI is performed with local anaesthesia only (33%), with associated conscious sedation (60%), or under general anaesthesia (7%). Primary vascular access is percutaneous transfemoral (99%) with secondary radial access (52%). After uncomplicated TAVI, patients are transferred to a high-, medium-, or low-care unit in 28%, 52%, and 20% of cases, respectively. Time to discharge is day 1 (12%), day 2 (31%), day 3 (29%), or day 4 or more (28%).ConclusionReported adoption of minimalist TAVI techniques is common among European TAVI centres, but rates of next-day discharge remain low. This survey highlights the significant progress made in refining TAVI treatment and pathways in recent years and identifies possible areas for further improvement

managing acute coronary syndrome caused by plaque erosion without stent implantation: a word of caution

status: publishe

Cost Projection of State of the Art Lithium-Ion Batteries for Electric Vehicles Up to 2030

The negative impact of the automotive industry on climate change can be tackled by changing from fossil driven vehicles towards battery electric vehicles with no tailpipe emissions. However their adoption mainly depends on the willingness to pay for the extra cost of the traction battery. The goal of this paper is to predict the cost of a battery pack in 2030 when considering two aspects: firstly a decade of research will ensure an improvement in material sciences altering a battery’s chemical composition. Secondly by considering the price erosion due to the production cost optimization, by maturing of the market and by evolving towards to a mass-manufacturing situation. The cost of a lithium Nickel Manganese Cobalt Oxide (NMC) battery (Cathode: NMC 6:2:2 ; Anode: graphite) as well as silicon based lithium-ion battery (Cathode: NMC 6:2:2 ; Anode: silicon alloy), expected to be on the market in 10 years, will be predicted to tackle the first aspect. The second aspect will be considered by combining process-based cost calculations with learning curves, which takes the increasing battery market into account. The 100 dollar/kWh sales barrier will be reached respectively between 2020-2025 for silicon based lithium-ion batteries and 2025–2030 for NMC batteries, which will give a boost to global electric vehicle adoption

Low Cytochrome Oxidase 1 Links Mitochondrial Dysfunction to Atherosclerosis in Mice and Pigs

<div><p>Background</p><p>Cytochrome oxidase IV complex regulates energy production in mitochondria. Therefore, we determined the relation of COX genes with atherosclerosis in mice and pigs.</p><p>Methods and results</p><p>First, we compared atherosclerosis in the aortic arch of age-matched (24 weeks) C57BL/6J control (n = 10), LDL-receptor deficient (n = 8), leptin-deficient ob/ob (n = 10), and double knock-out (lacking LDL-receptor and leptin) mice (n = 12). Low aortic <i>mitochondria-encoded cytochrome oxidase 1</i> in obese diabetic double knock-out mice was associated with a larger plaque area and higher propensity of M1 macrophages and oxidized LDL. Caloric restriction increased <i>mitochondria-encoded cytochrome oxidase 1</i> and reduced plaque area and oxidized LDL. This was associated with a reduction of titer of anti-oxidized LDL antibodies, a proxy of systemic oxidative stress. Low of <i>mitochondria-encoded cytochrome oxidase 1</i> was related to low expression of peroxisome proliferative activated receptors α, δ, and γ and of peroxisome proliferative activated receptor, gamma, co-activator 1 alpha reflecting mitochondrial dysfunction. Caloric restriction increased them. To investigate if there was a diabetic/obesity requirement for <i>mitochondria-encoded cytochrome oxidase 1</i> to be down-regulated, we then studied atherosclerosis in LAD of hypercholesterolemic pigs (n = 37). Pigs at the end of the study were divided in three groups based on increasing LAD plaque complexity according to Stary (Stary I: n = 12; Stary II: n = 13; Stary III: n = 12). Low <i>mitochondria-encoded cytochrome oxidase 1</i> in isolated plaque macrophages was associated with more complex coronary plaques and oxidized LDL. Nucleus-encoded cytochrome oxidase <i>4I1</i> and cytochrome oxidase <i>10</i> did not correlate with plaque complexity and oxidative stress. In mice and pigs, <i>MT-COI</i> was inversely related to insulin resistance.</p><p>Conclusions</p><p>Low <i>MT-COI</i> is related to mitochondrial dysfunction, oxidative stress and atherosclerosis and plaque complexity.</p></div