Publications

Aims This study aimed to use an umbrella review methodology to capture the range of outcomes that were associated with low‐dose aspirin and to systematically assess the credibility of this evidence. Methods Aspirin is associated with several health outcomes, but the overall benefit/risk balance related to aspirin use is unclear. We searched three major databases up to 15 August 2019 for meta‐analyses of observational studies and randomized controlled trials (RCTs) including low‐dose aspirin compared to placebo or other treatments. Based on random‐effects summary effect sizes, 95% prediction intervals, heterogeneity, small‐study effects and excess significance, significant meta‐analyses of observational studies were classified from convincing (class I) to weak (class IV). For meta‐analyses of RCTs, outcomes with random effects P ‐value < .005 and a moderate/high GRADE assessment, were classified as strong evidence. From 6802 hits, 67 meta‐analyses (156 outcomes) were eligible. Results Observational data showed highly suggestive evidence for aspirin use and increased risk of upper gastrointestinal bleeding (RR = 2.28, 95% CI: 1.97–2.64). In RCTs of low‐dose aspirin, we observed strong evidence for lower risk of CVD in people without CVD (RR = 0.83; 95% CI: 0.79–0.87) and in general population (RR = 0.83; 95% CI: 0.79–0.89), higher risk of major gastrointestinal (RR = 1.47; 95% CI: 1.26–1.72) and intracranial bleeding (RR = 1.34; 95% CI: 1.18–1.53), and of major bleedings in people without CVD (RR = 1.62; 95% CI: 1.26–2.08). Conclusion Compared to other active medications, low‐dose aspirin had strong evidence for lower risk of bleeding, but also lower comparative efficacy. Low‐dose aspirin significantly lowers CVD risk and increases risk of bleeding. Evidence for multiple other health outcomes is limited.

A folded multitap transmitter equalizer and multitap receiver equalizer counteract the losses and reflections present in the backplane environment. A flexible 2-PAM/4-PAM clock data recovery circuit uses select transitions for receive clock recovery. Bit-error rate less than 10/sup -15/ and power equal to 40 mW/Gb/s has been measured when operating over a 20-in backplane with two connectors at 10 Gb/s.

Genome-wide association studies (GWAS) have led to a rapid increase in available data on common genetic variants and phenotypes and numerous discoveries of new loci associated with susceptibility to common complex diseases. Integrating the evidence from GWAS and candidate gene studies depends on concerted efforts in data production, online publication, database development, and continuously updated data synthesis. Here the authors summarize current experience and challenges on these fronts, which were discussed at a 2008 multidisciplinary workshop sponsored by the Human Genome Epidemiology Network. Comprehensive field synopses that integrate many reported gene-disease associations have been systematically developed for several fields, including Alzheimer's disease, schizophrenia, bladder cancer, coronary heart disease, preterm birth, and DNA repair genes in various cancers. The authors summarize insights from these field synopses and discuss remaining unresolved issues -- especially in the light of evidence from GWAS, for which they summarize empirical P-value and effect-size data on 223 discovered associations for binary outcomes (142 with P < 10(-7)). They also present a vision of collaboration that builds reliable cumulative evidence for genetic associations with common complex diseases and a transparent, distributed, authoritative knowledge base on genetic variation and human health. As a next step in the evolution of Human Genome Epidemiology reviews, the authors invite investigators to submit field synopses for possible publication in the American Journal of Epidemiology.

This paper presents new image sensors with multi- bucket pixels that enable time-multiplexed exposure, an alter- native imaging approach. This approach deals nicely with scene motion, and greatly improves high dynamic range imaging, structured light illumination, motion corrected photography, etc. To implement an in-pixel memory or a bucket, the new image sensors incorporate the virtual phase CCD concept into a standard 4-transistor CMOS imager pixel. This design allows us to create a multi-bucket pixel which is compact, scalable, and supports true correlated double sampling to cancel kTC noise. Two image sensors with dual and quad-bucket pixels have been designed and fabricated. The dual-bucket sensor consists of a 640 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</sub> × 576 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</sub> array of 5.0 μm pixel in 0.11 μm CMOS technology while the quad-bucket sensor comprises 640 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</sub> × 512 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</sub> array of 5.6 μm pixel in 0.13 μm CMOS technology. Some computational photography applications were implemented using the two sensors to demonstrate their values in eliminating artifacts that currently plague computational photography.

Eur J Clin Invest 2010; 40 (2): 172–182 Abstract Background Most clinical trials on medical interventions are sponsored by the industry. The choice of comparators shapes the accumulated evidence. We aimed to assess how often major companies sponsor trials that involve only their own products. Methods Studies were identified by searching ClinicalTrials.gov for trials registered in 2006. We focused on randomized trials involving the 15 companies that had sponsored the largest number of registered trials in ClinicalTrials.gov in that period. Results Overall, 577 randomized trials were eligible for analysis and 82% had a single industry sponsor [89% (166/187) of the placebo‐control trials, 87% (91/105) of trials comparing different doses or ways of administration of the same intervention, and 78% (221/285) of other active control trials]. The compared intervention(s) belonged to a single company in 67% of the trials (89%, 81% and 47% in the three categories respectively). All 15 companies strongly preferred to run trials where they were the only industry sponsor or even the only owner of the assessed interventions. Co‐sponsorship typically reflected co‐ownership of the same intervention by both companies. Head‐to‐head comparison of different active interventions developed by different companies occurred in only 18 trials with two or more industry sponsors. Conclusions Each company generates a clinical research agenda that is strongly focused on its own products, while comparisons involving different interventions from different companies are uncommon. This diminishes the ability to understand the relative merits of different interventions for the same condition.

This paper presents methods for efficient energy-performance optimization at the circuit and micro-architectural levels. The optimal balance between energy and performance is achieved when the sensitivity of energy to a change in performance is equal for all the design variables. The sensitivity-based optimizations minimize energy subject to a delay constraint. Energy savings of about 65% can be achieved without delay penalty with equalization of sensitivities to sizing, supply, and threshold voltage in a 64-bit adder, compared to the reference design sized for minimum delay. Circuit optimization is effective only in the region of about /spl plusmn/30% around the reference delay; outside of this region the optimization becomes too costly either in terms of energy or delay. Using optimal energy-delay tradeoffs from the circuit level and introducing more degrees of freedom, the optimization is hierarchically extended to higher abstraction layers. We focus on the micro-architectural optimization and demonstrate that the scope of energy-efficient optimization can be extended by the choice of circuit topology or the level of parallelism. In a 64-bit ALU example, parallelism of five provides a three-fold performance increase, while requiring the same energy as the reference design. Parallel or time-multiplexed solutions significantly affect the area of their respective designs, so the overall design cost is minimized when optimal energy-area tradeoff is achieved.

Abstract Background: We evaluated whether articles on molecular diagnostic tests interpret appropriately the clinical applicability of their results. Methods: We selected original-research articles published in 2006 that addressed the diagnostic value of a molecular test. We defined overinterpretation of clinical applicability by means of prespecified rules that evaluated study design, conclusions regarding applicability, presence of statements suggesting the need for further clinical evaluation of the test, and diagnostic accuracy. Two reviewers independently evaluated the articles; consensus was reached after discussion and arbitration by a third reviewer. Results: Of 108 articles included in the study, 82 (76%) used a design that used healthy controls or alternative-diagnosis controls, only 15 (11%) addressed a clinically relevant population similar to that in which the test might be applied in practice, 104 articles (96%) made definitely favorable or promising statements regarding clinical applicability, and 61 (56%) of the articles apparently overinterpreted the clinical applicability of their findings. Articles published in journals with higher impact factors were more likely to overinterpret their results than those with lower impact factors (adjusted odds ratio, 1.71 per impact factor quartile; 95% CI, 1.09–2.69; P = 0.020). Overinterpretation was more common when authors were based in laboratories than in clinical settings (adjusted odds ratio, 18.7; 95% CI, 1.41–249; P = 0.036). Conclusions: Although expectations are high for new diagnostic tests based on molecular techniques, the majority of published research has involved preclinical phases of research. Overinterpretation of the clinical applicability of findings for new molecular diagnostic tests is common.

Due to their high volume, general-purpose processors, and now chip multiprocessors (CMPs), are much more cost effective than ASICs, but lag significantly in terms of performance and energy efficiency. This paper explores the sources of these performance and energy overheads in general-purpose processing systems by quantifying the overheads of a 720p HD H.264 encoder running on a general-purpose CMP system. It then explores methods to eliminate these overheads by transforming the CPU into a specialized system for H.264 encoding. We evaluate the gains from customizations useful to broad classes of algorithms, such as SIMD units, as well as those specific to particular computation, such as customized storage and functional units.

Simulation is the primary method for evaluating computer systems during all phases of the design process. One significant problem with simulation is that it rarely models the system exactly, and quantifying the resulting simulator error can be difficult. More importantly, architects often assume without proof that although their simulator may make inaccurate absolute performance predictions, it will still accurately predict architectural trends.This paper studies the source and magnitude of error in a range of architectural simulators by comparing the simulated execution time of several applications and microbenchmarks to their execution time on the actual hardware being modeled. The existence of a hardware gold standard allows us to find, quantify, and fix simulator inaccuracies. We then use the simulators to predict architectural trends and analyze the sensitivity of the results to the simulator configuration. We find that most of our simulators predict trends accurately, as long as they model all of the important performance effects for the application in question. Unfortunately, it is difficult to know what these effects are without having a hardware reference, as they can be quite subtle. This calls into question the value, for architectural studies, of highly detailed simulators whose characteristics are not carefully validated against s real hardware design.