The eigenspectra of Indian musical drums

In a family of drums used in the Indian subcontinent, the circular drum head is made of material of non-uniform density. Remarkably, and in contrast to a circular membrane of uniform density, the low eigenmodes of the non-uniform membrane are harmonic. In this work we model the drum head by a non-uniform membrane whose density varies smoothly between two prescribed values. Using a Fourier-Chebyshev spectral collocation method we obtain the eigenmodes and eigenvalues of the drum head. For a suitable choice of parameters, which we find by optimising a cost function, the eigenspectra obtained from our model are in excellent agreement with experimental values. Our model and the numerical method should find application in numerical sound synthesis

Synchronization of Sound Sources

Sound generation and -interaction is highly complex, nonlinear and self-organized. Already 150 years ago Lord Rayleigh raised the following problem: Two nearby organ pipes of different fundamental frequencies sound together almost inaudibly with identical pitch. This effect is now understood qualitatively by modern synchronization theory (M. Abel et al., J. Acoust. Soc. Am., 119(4), 2006). For a detailed, quantitative investigation, we substituted one pipe by an electric speaker. We observe that even minute driving signals force the pipe to synchronization, thus yielding three decades of synchronization -- the largest range ever measured to our knowledge. Furthermore, a mutual silencing of the pipe is found, which can be explained by self-organized oscillations, of use for novel methods of noise abatement. Finally, we develop a specific nonlinear reconstruction method which yields a perfect quantitative match of experiment and theory.Comment: 5 pages, 4 figure

Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria

Objective: We investigated if the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to irbesartan, and the effect of the combination. Research Design and Methods: Double-blind, randomized, cross-over trial. After a one-month washout period 26 patients with type 2 diabetes, hypertension and albuminuria (>100mg/day) were randomized to four 2-month treatment periods in random order with placebo, aliskiren 300 mg once daily, irbesartan 300 mg once daily or the combination using identical doses. Patients received furosemide in a stable dose throughout the study. Primary endpoint was change in albuminuria. Secondary measures included change in 24h blood pressure (24h BP) and glomerular filtration rate (GFR). Results: Placebo geometric mean albuminuria was 258 mg/day (range 84-2361), mean 24h BP was 140/73 (SD 15/8) mmHg, GFR was 89 (SD 27) ml/min/1.73 m(2). Aliskiren treatment reduced albuminuria by 48% (95% confidence interval 27-62) compared to placebo (p<0.001), not significantly different from irbesartan treatment (58% (42-70) (p<0.001 vs. placebo)). Combination treatment reduced albuminuria by 71% (59-79), more than either monotherapy (p<0.001 and p=0.028). Fractional clearances of albumin were significantly reduced (46, 56 and 67% reduction vs. placebo). 24h BP was reduced 3/4 mmHg by aliskiren (NS/p=0.009), 12/5 mmHg by irbesartan (p<0.001/p=0.002) and 10/6 mmHg by the combination (p=0.001/p<0.001). GFR was significantly reduced 4.6 (0.3, 8.8) ml/min/1.73m(2) by aliskiren, 8.0 (3.6, 12.3) ml/min/1.73m(2) by irbesartan and 11.7 (7.4, 15.9) ml/min/1.73m(2) by the combination. Conclusions: Combining aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria as compared to monotherapy

Advanced iontronic spiking modes with multiscale diffusive dynamics in a fluidic circuit

Fluidic iontronics is emerging as a distinctive platform for implementing neuromorphic circuits, characterised by its reliance on the same aqueous medium and ionic signal carriers as the brain. Drawing upon recent theoretical advancements in both iontronic spiking circuits and in dynamic conductance of conical ion channels, which form fluidic memristors, we expand the repertoire of proposed neuronal spiking dynamics in iontronic circuits. Through a modelled circuit containing channels that carry a bipolar surface charge, we extract phasic bursting, mixed-mode spiking, tonic bursting, and threshold variability, all with spike voltages and frequencies within the typical range for mammalian neurons. These features are possible due to the strong dependence of the typical conductance memory retention time on the channel length, enabling timescales varying from individual spikes to bursts of multiple spikes within a single circuit. These advanced forms of neuronal-like spiking support the exploration of aqueous iontronics as an interesting platform for neuromorphic circuits

Advanced iontronic spiking modes with multiscale diffusive dynamics in a fluidic circuit

Fluidic iontronics is emerging as a distinctive platform for implementing neuromorphic circuits, characterized by its reliance on the same aqueous medium and ionic signal carriers as the brain. Drawing upon recent theoretical advancements in both iontronic spiking circuits and in dynamic transport of aqueous electrolytes through conical ion channels, which form fluidic memristors, we expand the repertoire of proposed neuronal spiking dynamics in iontronic circuits. Through a modelled circuit containing channels that carry a bipolar surface charge, we extract phasic bursting, mixed-mode spiking, tonic bursting, and threshold variability, all with spike voltages and frequencies within the typical range for mammalian neurons. These features are possible due to the strong dependence of the typical conductance memory retention time on the channel length, enabling timescales varying from individual spikes to bursts of multiple spikes within a single circuit. These advanced forms of neuronal-like spiking support the exploration of aqueous iontronics as an interesting platform for neuromorphic circuits

Biharmonic pattern selection

A new model to describe fractal growth is discussed which includes effects due to long-range coupling between displacements $u$. The model is based on the biharmonic equation $\nabla^{4}u =0$ in two-dimensional isotropic defect-free media as follows from the Kuramoto-Sivashinsky equation for pattern formation -or, alternatively, from the theory of elasticity. As a difference with Laplacian and Poisson growth models, in the new model the Laplacian of $u$ is neither zero nor proportional to $u$. Its discretization allows to reproduce a transition from dense to multibranched growth at a point in which the growth velocity exhibits a minimum similarly to what occurs within Poisson growth in planar geometry. Furthermore, in circular geometry the transition point is estimated for the simplest case from the relation $r_{\ell}\approx L/e^{1/2}$ such that the trajectories become stable at the growing surfaces in a continuous limit. Hence, within the biharmonic growth model, this transition depends only on the system size $L$ and occurs approximately at a distance $60 \%$ far from a central seed particle. The influence of biharmonic patterns on the growth probability for each lattice site is also analysed.Comment: To appear in Phys. Rev. E. Copies upon request to [email protected]

Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial

Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25–75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. Findings: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0–2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52–0·79) and those without diabetes (0·50, 0·35–0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45–0·73] vs 0·51 [0·34–0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53–0·92] vs 0·79 [0·40–1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56–0·98] vs 0·52 [0·29–0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51–0·78), glomerulonephritides (n=695; 0·43, 0·26–0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44–1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29–1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. Interpretation: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease

Breast-feeding and risk of epithelial ovarian cancer.

Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype