The use of magnetic material can improve the performance of a single-flux-quantum device by inducing high self-or mutual inductance, which can reduce the size or increase the sensitivity of the device. We used magnetic nanoparticles as the magnetic material and adopted photoresist patterns with Fe 3 O 4 nanoparticles as a means of inserting nanoparticles into a device. The effect of the nanoparticles was investigated for SQUIDs with photoresist patterns. Analytical estimation of the effect indicated a variation in SQUID inductance of less than 1%, which is in agreement with the experimental results in the absence of external magnetic fields. On the other hand, when external DC magnetic fields were applied, a slight increase in inductance was observed for several SQUIDs.

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We evaluated the effects of Fe3O4 magnetic nanoparticle (NP) films on the electrical characteristics of superconducting quantum interference devices (SQUIDs) at 4.2 K to enhance the performance of superconducting circuits. The NP films were formed directly on the SQUIDs. For SQUIDs with 5-nm-NP films, the SQUID inductance increased almost linearly with the NP film thickness, reaching 19.7% at an NP film thickness of 990 nm. An increase in NP size from 5 to 20 nm reduced that in the SQUID inductance. On the other hand, no clear effects on the current–voltage characteristics of SQUIDs were observed for 5- and 10-nm-NP films, while the critical currents of some SQUIDs with 20-nm-NP films were reduced.

Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a rapidly progressive, multisystem disease. Orthostatic hypotension, due to autonomic neuropathy, is a common yet hard-to-treat disease manifestation in patients with hATTR amyloidosis. Fatigue, muscle weakness, and deterioration in cardiac function further exacerbate orthostatic symptoms. Efficacy of RNAi therapeutics patisiran and vutrisiran was assessed in patients with hATTR amyloidosis with polyneuropathy across the APOLLO (NCT01960348), Global Open-Label Extension (OLE) (NCT02510261), and HELIOS-A (NCT03759379) studies, respectively. Purpose Evaluate the quantitative effect of patisiran and vutrisiran on orthostatic hypotension in patients with hATTR amyloidosis with polyneuropathy. Methods In APOLLO, patients were randomised 2:1 to patisiran 0.3 mg/kg or placebo, IV q3w. Patients who completed APOLLO (APOLLO-placebo, APOLLO-patisiran) were eligible to enrol into the ongoing Global OLE (patisiran 0.3 mg/kg IV q3w). In HELIOS-A, patients were randomised 3:1 to vutrisiran (25 mg SC q3m) or patisiran (0.3 mg/kg IV q3w; reference group). Primary endpoint for APOLLO and HELIOS-A was change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7) vs APOLLO placebo at M18 (APOLLO) and M9 (HELIOS-A). Orthostatic hypotension was evaluated using the postural blood pressure (PBP) component of mNIS+7, calculated as the mean of 2 supine readings of systolic BP [SBP, mmHg] taken 15 min apart minus the lowest SBP upon standing at 1, 3, and 5 min. A smaller reduction in observed SBP between supine and upright readings indicated an improved PBP. Results APOLLO enrolled 225 patients (placebo, n=77; patisiran, n=148), Global OLE 211 and HELIOS-A 164 (vutrisiran, n=122; patisiran, n=42). At baseline, the severity of orthostatic hypotension was similar between within-study treatment arms in APOLLO and HELIOS-A. In APOLLO, patisiran-treated patients showed PBP improvement or stabilization from baseline to M18 (mean [SD] change in SBP: baseline, −17.6 [19.4]; M18, −13.5 [16.8]) and was maintained at Global OLE 36m (−13.4 [15.6]). In contrast, placebo-treated patients in APOLLO had an increased change in PBP over 18m (baseline, −17.5 [16.5]; M18, −20.4 [16.9]); their PBP improved after patisiran initiation (Global OLE 36m, −16.6 [18.1]). In HELIOS-A, stabilization in PBP was observed in the vutrisiran arm (baseline, −11.2 [14.0], M18, −11.7 [14.6]). In the smaller patisiran arm, while the change in PBP increased, the value remained in the normal range (baseline, −11.6 [17.2]; M18, −14.2 [15.5]). Patisiran and vutrisiran have acceptable safety profiles. Conclusions PBP analyses quantify the benefits of RNAi therapeutics patisiran and vutrisiran on autonomic function in patients with hATTR amyloidosis with polyneuropathy. The increase in change in PBP to a symptomatic range without treatment indicates the importance of early intervention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Alnylam Pharmaceuticals

Background In heart failure with reduced ejection fraction (HFrEF), drugs including angiotensin-converting enzyme inhibitors (ACEi)/ angiotensin receptor blockers (ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA) have been shown to have robust survival benefits. However, these guideline-recommended therapies remain underutilized in clinical practice. Frailty is common in HFrEF and may lead to underprescription of life-saving therapy. Purpose We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for HFrEF, and the impact of this on prognosis Methods The FLAGSHIP study included patients hospitalized for acute HF and data on physical frailty were collected prospectively. Of the total 3,272 patients registered in the FLAGSHIP study, 1,041 HFrEF patients (70 years; 73% male) with left ventricular ejection fraction ≤40% were analyzed and were divided into 4 groups by severity of frailty: category I (n=371) [least frail], II (n=275), III (n=224), and IV (n=171) [most frail]. Results An ACEi/ARB was prescribed in 76% of category I and 53% of category IV patients; for a beta-blocker these proportions were 94% and 76%, respectively; for an MRA they were 55% and 46%, respectively. The proportion of patients using receiving all 3 drugs decreased as frailty increased, with approximately twice the rate of use of triple therapy in category I patients (40.2%) compared to category IV patients (23.4%) [p<0.001] (Figure 1). In adjusted analyses, the severity of frailty was an independent predictor for non-use of an ACEi/ARB (Odds ratio (OR): 1.23, 95% CI: 1.05–1.43, per 1 category increase) and a beta-blocker (OR: 1.32, 95% CI: 1.06–1.64), but not an MRA (OR: 0.97, 95% CI: 0.84–1.12). Risk of the composite outcome of all-cause death or HF rehospitalization increased with decreasing use of treatment across frailty categories: category I-II (Hazard ratio (HR): 1.80, 95% CI: 1.08–2.98, in 0–1 drug with 3 drugs as reference) and III–IV (HR: 1.53, 95% CI: 1.01–2.32). The relationship between the number of HF drugs prescribed and the composite outcome did not differ across frailty categories (p-interaction=0.86). The HRs for all 12 groups, reflecting frailty categories and a number of HF drugs is depicted in Figure 2. The HRs for composite outcome increased with increasing frailty category and with decreasing number of drugs, with an almost 4-fold difference in risk between the least frail patients receiving all three evidence-based therapies and the most frail receiving only 0–1 drug. Conclusions Prescription of guideline-recommended therapy decreased as the severity of frailty increased in patients with HFrEF. Sub-optimal medical therapy was associated with a worse outcome and underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with frailty. An effective strategy is needed to improve the medical treatment of frail patients with HFrEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study issupported by a Grant-in-Aid for Scientifi c Research (A) from the Japan Society for the Promotion of Science (16H01862). ToruKondo receives grants from the Uehara Memorial Foundation and the Japanese Heart Failure Society Tsuchiya Foundation forthe research activities at the University of Glasgow.