mechanoluminescence of nylon under high velocity impact

The light emissions produced during deformation of solids induced by any mechanical action is called mechanoluminescence (ML). This phenomenon was reported mostly in hypervelocity impacts. Using high speed video-recording, the authors found evidence of ML for nylon at much lower impact velocity (of the order of 100 m/s). In order to understand the mechanism responsible for ML, Taylor impact experiments were planned and performed. Several impact configurations were investigated: Taylor anvil impact, Taylor impact on nylon anvil and rod-on-rod impact experiment. During the tests, the emitted light was measured using a wide-spectrum visible-to-infrared photodiode with response below 1 microsecond, and the signals were analyzed. The existence of a limiting impact velocity below which ML is no longer observed seems to be indicative of the fact that ML is controlled by the high pressure that is generated under uniaxial strain loading conditions. This result is consistent with the fact that, as soon as the compressive stress wave travels longitudinally in the Taylor sample and the pressure drops as a result of the arrival of the release waves, the ML no longer occurs. When tests were repeated in vacuum, no light emission in the visible range was observed. This finding seems to indicate that light emission occurs as a result of the oxidation of free radicals generated by the rupture of the polymer chains caused by the dynamic pressure wave

Effects of Bisphosphonate Treatment on Circulating Lipid and Glucose Levels in Patients with Metabolic Bone Disorders

Bisphosphonates are the first-choice treatment of osteoporosis and Paget’s disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget’s disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations

Radiation performance of new semiconductor power devices for the LHC experiment upgrades

11th International Conference on Large Scale Applications and Radiation Hardness of Semiconductor Detectors, RD 201

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Pathophysiological Role of Synovitis in Hemophilic Arthropathy Development: A Two-Hit Hypothesis

Despite an increasing access to prophylaxis with clotting factor concentrates, arthropathy still represents the main chronic complication of hemophilia. Whereas previous studies described hemophilic arthropathy (HA) as a degenerative arthropathy, somehow resembling osteoarthritis (OA), most recent evidence suggests that complex inflammatory and immunologic mechanisms are also involved in the pathophysiology of HA. In the present review, we described available data on major mechanisms leading to arthropathic changes in patients with hemophilia, with a specific focus on the role of synovium. The presence of hemosiderin in the joint space induces synovium proliferation, thus leading to formation of several lytic enzymes determining chondrocytes apoptosis and proteoglycans levels reduction. This leads to a direct joint “chemical” damage representing early damages in the pathogenesis of HA (first hit). In parallel, synovial membrane and synovial endothelial cells become a dynamic reservoir of inflammatory cells and mediators, and propagate the inflammatory response (second hit), switching the process from a chemical damage to an inflammatory damage. Overall, consistent data pointed out synovitis as the keystone in HA pathophysiology. This opens novel potential therapeutic targets in this clinical setting