Aims: This study aimed to compare outcomes in unselected patients undergoing cardiac catheterisation via transradial versus transfemoral access and standard versus ultrasound-guided arterial access.Methods and results: This was a prospective, randomised (radial vs femoral and standard vs ultrasound), 2x2 factorial trial of 1,388 patients undergoing coronary angiography and percutaneous coronary intervention. The primary outcome was a composite of ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) major bleeding, MACE (death, stroke, myocardial infarction or urgent target lesion revascularisation) and vascular complications at 30 days. Transradial access reduced the primary outcome (RR 0.37, 95% CI: 0.17-0.81; p=0.013), mostly driven by ACUITY major bleeding (RR 0.343, 95% CI: 0.123-0.959; p=0.041) when compared with the transfemoral approach. There was no difference in the primary outcome between standard and ultrasound guidance (p=0.76). Ultrasound guidance, however, reduced mean access time (93 sec vs 111 sec; p=0.009), attempts (1.47 vs 1.9; p<0.0001), difficult accesses (4.5% vs 9.2%; p=0.0007), venepuncture (4.1% vs 9.2%; p<0.0001) and improved first-pass success (73% vs 59.7%; p<0.0001).Conclusions: Transradial access significantly reduced the composite outcome compared to transfemoral access. Ultrasound guidance did not reduce the primary outcome compared to the standard technique, but significantly improved the efficiency and overall success rate of arterial access.
Nutrient-deprived conditions in the tumor microenvironment (TME) restrain cancer cell viability due to increased free radicals and reduced energy production. In pancreatic cancer cells a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables adaptation to these conditions. Under nutrient starvation, wtIDH1 oxidizes isocitrate to generate α-ketoglutarate (αKG) for anaplerosis and NADPH to support antioxidant defense. In this study, we show that allosteric inhibitors of mutant IDH1 (mIDH1) are potent wtIDH1 inhibitors under conditions present in the TME. We demonstrate that low magnesium levels facilitate allosteric inhibition of wtIDH1, which is lethal to cancer cells when nutrients are limited. Furthermore, the Food & Drug Administration (FDA)-approved mIDH1 inhibitor ivosidenib (AG-120) dramatically inhibited tumor growth in preclinical models of pancreatic cancer, highlighting this approach as a potential therapeutic strategy against wild-type IDH1 cancers.
A continuous bubble-column scrubber that absorbs carbon dioxide (CO2) gas using an alkaline solution under a pH-stat condition was used to explore the effects of the pH of the solution, gas concentration, gas-superficial velocity, and liquid-flow rate on the absorption rate and volumetric mass-transfer coefficient of CO2. When the scrubbing factor was evaluated, this scrubber outperformed other scrubbers. Correlations of local volumetric mass-transfer coefficients with process variables are presented here and the gas−liquid interfacial area and individual mass-transfer coefficient are discussed to provide insight into the mass-transfer mechanism. Investigation of the liquid-side mass transfer coefficient revealed that the k L/[OH−]0.5 value was a constant, thus demonstrating that the system obeyed second-order kinetics. Evidence also shows that liquid-side resistances are within the range of 27%−99%, indicating that gas-side mass-transfer resistance cannot be neglected in some cases. This implies that the absorption mechanism is flexible and can be shifted by adjusting the process parameters.
Cancer cells in culture rely on glutamine as an anaplerotic substrate to replenish tricarboxylic acid (TCA) cycle intermediates that have been consumed. but it is uncertain whether cancers in vivo depend on glutamine for anaplerosis. Here, following in vivo infusions of [13C5]-glutamine in mice bearing subcutaneous colon cancer xenografts, we showed substantial amounts of infused [13C5]-glutamine enters the TCA cycle in the tumors. Consistent with our prior observation that colorectal cancers (CRCs) with oncogenic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic (PIK3CA) subunit are more dependent on glutamine than CRCs with wild type PIK3CA, labeling from glutamine to most TCA cycle intermediates was higher in PIK3CA-mutant subcutaneous xenograft tumors than in wild type PIK3CA tumors. Moreover, using orthotopic mouse colon tumors estalished from human CRC cells or patient-derived xenografts, we demonstrated substantial amounts of infused [13C5]-glutamine enters the TCA cycle in the tumors and tumors utilize anaplerotic glutamine to a greater extent than adjacent normal colon tissues. Similar results were seen in spontaneous colon tumors arising in genetically engineered mice. Our studies provide compelling evidence CRCs utilizes glutamine to replenish the TCA cycle in vivo, suggesting that targeting glutamine metabolism could be a therapeutic approach for CRCs, especially for PIK3CA-mutant CRCs.
The edge devices in an emerging Internet-of-Things (IoT) environment require comprehensive security measures that are within the power budget for ubiquitous computing. In this paper, a transmitter identification scheme consisting of a lightweight Bayesian neural network (BNN)based classifier using raw time-domain data is presented. Evaluation is performed with data obtained in schematic-level simulation of high-efficiency CMOS power amplifier designs using a 65 nm process design kit (PDK). The Bayesian neural networks achieve 89.5% accuracy on the task of classifying six transmitters. Moreover, the BNN classifier is implemented on field-programmable gate array (FPGA) with parallel pseudo-Gaussian random number generators to achieve a throughput of more than 340,000 classifications per second, with average energy consumption for each classification task of 0.548 μJ. This low-power system enables comprehensive security for energy-constrained IoT devices and sensors.INDEX TERMS Hardware security, Bayesian neural networks, radio frequency and wireless circuits, power amplifier, Gaussian random number generator, radio frequency fingerprint, Internet of Things.
<b><i>Introduction:</i></b> Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. <b><i>Methods:</i></b> We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0–3 at 90 days. Secondary outcomes were mRS 0–3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). <b><i>Results:</i></b> Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; <i>p</i> = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; <i>p</i> = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; <i>p</i> = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59–2.43; <i>p</i> = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69–2.78; <i>p</i> = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55–2.43; <i>p</i> = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08–2.66; <i>p</i> = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03–3.09; <i>p</i> = 0.303) comparably low in both groups. <b><i>Conclusion:</i></b> Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.
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