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Stereoelectroencephalography in Pediatric Epilepsy Surgery
Tomlinson, Samuel B.,Buch, Vivek P.,Armstrong, Dallas,Kennedy, Benjamin C. The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.3
Stereoelectroencephalography (SEEG) is an invasive technique used during the surgical management of medically refractory epilepsy. The utility of SEEG rests in its ability to survey the three-dimensional organization of the epileptogenic zone as well as nearby eloquent cortices. Once concentrated to specialized centers in Europe and Canada, the SEEG methodology has gained worldwide popularity due to its favorable morbidity profile, superior coverage of deep structures, and ability to perform multi-lobar explorations without the need for craniotomy. This rapid shift in practice represents both a challenge and an opportunity for pediatric neurosurgeons familiar with the subdural grid approach. The purpose of this review is to discuss the indications, technique, and safety of long-term SEEG monitoring in children. In addition to reviewing the conceptual and technical points of the diagnostic evaluation, attention will also be given to SEEG-based interventions (e.g., radiofrequency thermo-coagulation).
Ethical Challenges for Stem Cell Research : From the Embryo to the Bedside
Tomlinson, Tom Ewha Institute for Biomedical Law & Ethics 2011 BIOMEDICAL LAW & ETHICS Vol.5 No.1
In this paper I discuss some key ethical challenges raised by stem cell-based research. After explaining the potential of stem cell research for developing effective new treatments for a variety of diseases, I explore whether the moral status of the human embryo should limit or prohibit research using embryonic stem cells. I turn next to further ethical challenges that will arise with the first human trials of stem cell-based treatments, even if the source of the stem cells poses no problem. Finally, I discuss the question of whether the use of induced pluripotent stem cells can successfully side-step questions about when a human life begins.
Hamish Tomlinson,Geoffrey W. Rodgers,Chao Xu,Virginie Avot,Cong Zhou,J. Geoffrey Chase 국제구조공학회 2023 Smart Structures and Systems, An International Jou Vol.31 No.2
Structural health monitoring (SHM) covers a range of damage detection strategies for buildings. In real-time, SHM provides a basis for rapid decision making to optimise the speed and economic efficiency of post-event response. Previous work introduced an SHM method based on identifying structural nonlinear hysteretic parameters and their evolution from structural force-deformation hysteresis loops in real-time. This research extends and generalises this method to investigate the impact of a wide range of flag-shaped or pinching shape nonlinear hysteretic response and its impact on the SHM accuracy. A particular focus is plastic stiffness (<i>k<sub>p</sup></>), where accurate identification of this parameter enables accurate identification of net and total plastic deformation and plastic energy dissipated, all of which are directly related to damage and infrequently assessed in SHM. A sensitivity study using a realistic seismic case study with known ground truth values investigates the impact of hysteresis loop shape, as well as added noise, on SHM accuracy using a suite of 20 ground motions from the PEER database. Monte Carlo analysis over 22,000 simulations with different hysteresis loops and added noise resulted in absolute percentage identification error (median, (IQR)) in <i>k<sub>p</sup></> of 1.88% (0.79, 4.94)%. Errors were larger where five events (Earthquakes #1, 6, 9, 14) have very large errors over 100% for resulted <i>k<sub>p</sup></> as an almost entirely linear response yielded only negligible plastic response, increasing identification error. The sensitivity analysis shows accuracy is reduces to within 3% when plastic drift is induced. This method shows clear potential to provide accurate, real-time metrics of non-linear stiffness and deformation to assist rapid damage assessment and decision making, utilising algorithms significantly simpler than previous non-linear structural model-based parameter identification SHM methods.
Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors
Brian Tomlinson,Qian-yan Wu,Yi-ming Zhong,Yan-hong Li 한국지질동맥경화학회 2024 지질·동맥경화학회지 Vol.13 No.1
Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins. Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs. However, it was found ANGPTL3 inhibitors were also effective in reducing low-density lipoprotein cholesterol (LDL-C) and they were studied in patients with homozygous familial hypercholesterolaemia (FH). Evinacumab targets ANGPTL3 and reduced LDL-C by about 50% in patients with homozygous FH and it has been approved for that indication. The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies. ApoC3 can be inhibited by the ASO volanesorsen, which reduced triglycerides by >70% in patients with FCS and it was approved for FCS in Europe but not in the United States because of concerns about thrombocytopaenia. Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. ARO-APOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies.
Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia
Brian Tomlinson,Nivritti Gajanan Patil,Manson Fok,Christopher Wai Kei Lam 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.2
Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygousFH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those withhomozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given bysubcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many ofthem to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-actingsmall interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C bymore than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonalantibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for themajority of patients with FH.