An Aliasing-Free Hybrid Digital-Analog Polyphonic Synthesizer

Analog subtractive synthesizers are generally considered to provide superior sound quality compared to digital emulations. However, analog circuitry requires calibration and suffers from aging, temperature instability, and limited flexibility in generating a wide variety of waveforms. Digital synthesis can mitigate many of these drawbacks, but generating arbitrary aliasing-free waveforms remains challenging. In this paper, we present the +-synth, a hybrid digital-analog eight-voice polyphonic synthesizer prototype that combines the best of both worlds. At the heart of the synthesizer is the big Fourier oscillator (BFO), a novel digital very-large scale integration (VLSI) design that utilizes additive synthesis to generate a wide variety of aliasing-free waveforms. Each BFO produces two voices, using four oscillators per voice. A single oscillator can generate up to 1024 freely configurable partials (harmonic or inharmonic), which are calculated using coordinate rotation digital computers (CORDICs). The BFOs were fabricated as 65nm CMOS custom application-specific integrated circuits (ASICs), which are integrated in the +-synth to simultaneously generate up to 32768 partials. Four 24-bit 96kHz stereo DACs then convert the eight voices into the analog domain, followed by digitally controlled analog low-pass filtering and amplification. Measurement results of the +-synth prototype demonstrate high fidelity and low latency.Comment: Presented at DAFx2

Drug dosing consideration in patients with acute and chronic kidney disease—a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO)

Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patient’s kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease