2,497 publications from this institution
This paper proposes a circuit optimization approach that can ease the computational burden on the simulation-based circuit optimizers by leveraging simple design equations that reflect the designer's intent. The technique is inspired by continuation methods (a.k.a. homotopy) in numerical analysis where a hard problem is solved by constructing an easier problem first and gradually refining its solution to that of the hard problem. In a circuit optimization context, the designer's simplified equations for the circuit serve as the easier problem. These simplified design equations are easy to write as they need not be completely accurate and have intuitive, well-understood solutions. Nonetheless, in several circuit examples, it was found that the designer's equations serve as better guidance than the conventional, fixed-point equations. As a result, the proposed approach demonstrates the better convergence to the desired solution with less computational efforts.
Medical and scientific advances are predicated on new knowledge that is robust and reliable and that serves as a solid foundation on which further advances can be built. In biomedical research, we are in the midst of a revolution with the generation of new data and scientific publications at a previously unprecedented rate. However, unfortunately, there is compelling evidence that the majority of these discoveries will not stand the test of time. To a large extent, this reproducibility crisis in basic and preclinical research may be as a result of failure to adhere to good scientific practice and the desperation to publish or perish. This is a multifaceted, multistakeholder problem. No single party is solely responsible, and no single solution will suffice. Here we review the reproducibility problems in basic and preclinical biomedical research, highlight some of the complexities, and discuss potential solutions that may help improve research quality and reproducibility.
Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.
ABSTRACT Different modeling approaches can be used to calculate excess deaths for the COVID-19 pandemic period. We compared 6 calculations of excess deaths (4 previously published and two new ones that we performed with and without age-adjustment) for 2020-2021. With each approach, we calculated excess deaths metrics and the ratio R of excess deaths over recorded COVID-19 deaths. The main analysis focused on 33 high-income countries with weekly deaths in the Human Mortality Database (HMD at mortality.org) and reliable death registration. Secondary analyses compared calculations for other countries, whenever available. Across the 33 high-income countries, excess deaths were 2.0-2.8 million without age-adjustment, and 1.6-2.1 million with age-adjustment with large differences across countries. In our analyses after age-adjustment, 8 of 33 countries had no overall excess deaths; there was a death deficit in children; and 0.478 million (29.7%) of the excess deaths were in people <65 years old. In countries like France, Germany, Italy, and Spain excess death estimates differed 2 to 4-fold between highest and lowest figures. The R values’ range exceeded 0.3 in all 33 countries. In 16 of 33 countries, the range of R exceeded 1. In 25 of 33 countries some calculations suggest R>1 (excess deaths exceeding COVID-19 deaths) while others suggest R<1 (excess deaths smaller than COVID-19 deaths). Inferred data from 4 evaluations for 42 countries and from 3 evaluations for another 98 countries are very tenuous Estimates of excess deaths are analysis-dependent and age-adjustment is important to consider. Excess deaths may be lower than previously calculated. SIGNIFICANCE STATEMENT Excess deaths are a key metric for assessing the impact of a pandemic. They reflect the composite impact of deaths from infection, from indirect pandemic effects, and from the measures taken. Different modeling approaches can be used to calculate excess deaths for the COVID-19 pandemic. Here, we compare four previous calculations of excess deaths and two new ones that we performed with and without adjusting for changing age structure in the estimation. Proper age-adjustment results in substantial reduction in estimates of excess deaths for 2020-2021. While results from different calculation methods are correlated, the absolute differences in estimated excess deaths are very high in most countries. Extrapolations to countries without reliable death registration is extremely tenuous.
The authors survey uncommon variants (minor allele frequency, ≤5%) that have reached genome-wide significance (P ≤ 10⁻⁷) in genome-wide association study(ies) (GWAS). They examine the typical effect sizes of these associations; whether they have arisen in multiple GWAS on the same phenotype; and whether they pertain to genetic loci that have other variants discovered through GWAS, perceived biologic plausibility from the candidate gene era, or known mutations associated with related phenotypes. Forty-three associations with minor allele frequency of 5% or less and P ≤ 10⁻⁷ were studied, 12 of which involved nonsynonymous variants. Per-allele odds ratios ranged from 1.03 to 22.11. Thirty-two associations had P ≤ 10⁻⁸. Eight uncommon variants were identified in multiple GWAS. For 14 associations, also other common polymorphisms with genome-wide significance were identified in the same loci. Thirteen associations pertained to genetic loci considered to have biologic plausibility for association in the candidate gene era, and mutations with related phenotypic effects were identified for 11 associations. Twenty-five uncommon variants are common in at least 1 of the 4 different ancestry samples of the International HapMap Project. Although the number of uncommon variants with genome-wide significance is still limited, these data suggest a possible confluence of rare/uncommon and common genetic variation on the same genetic loci.
A high speed CMOS signaling interface for application in multiprocessor interconnection networks has been developed. The interface utilizes I-V push-pull drivers, a delay line phase-locked loop (PLL), and sampling of the data on both edges of the clock. In order to increase the noise immunity of the reception, a current-integrating input pin sampler is used to receive the incoming data. Chips fabricated in a 0.8 /spl mu/m CMOS technology achieve transfer rates of 740 Mb/s/pin operating from a 3.3 V supply with a bit error rate of less than 10/sup -14/.
A 36-b (32-b words with byte parity) by 32-word triple-ported register file designed to be used as a macrocell in an emitter-coupled-logic (ECL) reduced-instruction-set-computer (RISC) microprocessor is discussed. The goal was to produce a dense, low-power design, since the floating-point coprocessor requires two register files. The chips are fabricated using a 2- mu m, triple-implanted, three-level metal bipolar process. This process yields small, low-capacitance transistors, ideal for running at low currents. The minimum-size transistor has a collector series resistance of 1500 Omega , so transistor sizing is very important in this technology. A standard ECL inverter running at an 80- mu A tail has a nominal delay of 350 ps. The metal pitches are 4 mu m on metal 1 and metal 2 and 8 mu m on metal 3.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
