Publications

AHA: An Agile Approach to the Design of Coarse-Grained Reconfigurable Accelerators and Compilers

With the slowing of Moore’s law, computer architects have turned to domain-specific hardware specialization to continue improving the performance and efficiency of computing systems. However, specialization typically entails significant modifications to the software stack to properly leverage the updated hardware. The lack of a structured approach for updating the compiler and the accelerator in tandem has impeded many attempts to systematize this procedure. We propose a new approach to enable flexible and evolvable domain-specific hardware specialization based on coarse-grained reconfigurable arrays (CGRAs). Our agile methodology employs a combination of new programming languages and formal methods to automatically generate the accelerator hardware and its compiler from a single source of truth. This enables the creation of design-space exploration frameworks that automatically generate accelerator architectures that approach the efficiencies of hand-designed accelerators, with a significantly lower design effort for both hardware and compiler generation. Our current system accelerates dense linear algebra applications but is modular and can be extended to support other domains. Our methodology has the potential to significantly improve the productivity of hardware-software engineering teams and enable quicker customization and deployment of complex accelerator-rich computing systems.

CONSORT 2025 statement: updated guideline for reporting randomised trials

Abstract Background Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. Methods We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. Results We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Conclusion Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

Guidance to best tools and practices for systematic reviews

Data continue to accumulate indicating that many systematic reviews are methodologically flawed, biased, redundant, or uninformative. Some improvements have occurred in recent years based on empirical methods research and standardization of appraisal tools; however, many authors do not routinely or consistently apply these updated methods. In addition, guideline developers, peer reviewers, and journal editors often disregard current methodological standards. Although extensively acknowledged and explored in the methodological literature, most clinicians seem unaware of these issues and may automatically accept evidence syntheses (and clinical practice guidelines based on their conclusions) as trustworthy. A plethora of methods and tools are recommended for the development and evaluation of evidence syntheses. It is important to understand what these are intended to do (and cannot do) and how they can be utilized. Our objective is to distill this sprawling information into a format that is understandable and readily accessible to authors, peer reviewers, and editors. In doing so, we aim to promote appreciation and understanding of the demanding science of evidence synthesis among stakeholders. We focus on well-documented deficiencies in key components of evidence syntheses to elucidate the rationale for current standards. The constructs underlying the tools developed to assess reporting, risk of bias, and methodological quality of evidence syntheses are distinguished from those involved in determining overall certainty of a body of evidence. Another important distinction is made between those tools used by authors to develop their syntheses as opposed to those used to ultimately judge their work. Exemplar methods and research practices are described, complemented by novel pragmatic strategies to improve evidence syntheses. The latter include preferred terminology and a scheme to characterize types of research evidence. We organize best practice resources in a Concise Guide that can be widely adopted and adapted for routine implementation by authors and journals. Appropriate, informed use of these is encouraged, but we caution against their superficial application and emphasize their endorsement does not substitute for in-depth methodological training. By highlighting best practices with their rationale, we hope this guidance will inspire further evolution of methods and tools that can advance the field.

Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study

Abstract Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.

Cytotoxic T-Lymphocyte Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Disease: A Meta-Analysis

The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.

Supply and threshold voltage scaling for low power CMOS

This paper investigates the effect of lowering the supply and threshold voltages on the energy efficiency of CMOS circuits. Using a first-order model of the energy and delay of a CMOS circuit, we show that lowering the supply and threshold voltage is generally advantageous, especially when the transistors are velocity saturated and the nodes have a high activity factor, In fact, for modern submicron technologies, this simple analysis suggests optimal energy efficiency at supply voltages under 0.5 V. Other process and circuit parameters have almost no effect on this optimal operating point. If there is some uncertainty in the value of the threshold or supply voltage, however, the power advantage of this very low voltage operation diminishes. Therefore, unless active feedback is used to control the uncertainty, in the future the supply and threshold voltage will not decrease drastically, but rather will continue to scale down to maintain constant electric fields.

High-impact trials with genetic and -omics information focus on cancer mutations, are industry-funded, and less transparent

Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a meta-analysis

Strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS): explanation and elaboration

A low power switching power supply for self-clocked systems

This paper presents a digital power supply controller for variable frequency and voltage circuits. By using a ring oscillator as a method of predicting circuit performance, the regulated voltage is set to the minimum required to operate at a reference frequency which maximizes energy efficiency. Our initial test silicon, implemented with a fixed frequency controller is analyzed and reveals that the controller's power consumption is a major limitation for such a design. To make the controller power dissipation scale with the CV/sup 2/f power of the load, we introduce a new architecture with variable frequency control, which allows the controller's supply and frequency to scale along with the load device.

Synopsis of Preterm Birth Genetic Association Studies: The Preterm Birth Genetics Knowledge Base (PTBGene)

<i>Aim:</i> Our goal wasto produce a field synopsis of genetic associations with preterm birth and to set up a publicly available online database summarizing the data. <i>Methods:</i> We performed a systematic review and meta-analyses to identify genetic associations with preterm birth. We have set up a publicly available online database of genetic association data on preterm birth called PTBGene (http://ric.einstein.yu.edu/ptbgene/index.html) and report on a structured synopsis thereof as of December 1, 2008. <i>Results:</i> Data on 189 polymorphisms in 84 genes have been included and 36 meta-analyses have been performed. Five gene variants (4 in maternal DNA, one in newborn DNA) have shown nominally significant associations, but all have weak epidemiological credibility. <i>Conclusion:</i> After publishing this field synopsis, the PTBGene database will be regularly updated to keep track of the evolving evidence base of genetic factors in preterm birth with the goal of promoting knowledge sharing and multicenter collaboration among preterm birth research groups.

Light field microscopy

By inserting a microlens array into the optical train of a conventional microscope, one can capture light fields of biological specimens in a single photograph. Although diffraction places a limit on the product of spatial and angular resolution in these light fields, we can nevertheless produce useful perspective views and focal stacks from them. Since microscopes are inherently orthographic devices, perspective views represent a new way to look at microscopic specimens. The ability to create focal stacks from a single photograph allows moving or light-sensitive specimens to be recorded. Applying 3D deconvolution to these focal stacks, we can produce a set of cross sections, which can be visualized using volume rendering. In this paper, we demonstrate a prototype light field microscope (LFM), analyze its optical performance, and show perspective views, focal stacks, and reconstructed volumes for a variety of biological specimens. We also show that synthetic focusing followed by 3D deconvolution is equivalent to applying limited-angle tomography directly to the 4D light field.

The rapid, massive growth of COVID-19 authors in the scientific literature

ABSTRACT We examined the extent to which the scientific workforce in different fields was engaged in publishing COVID-19-related papers. According to Scopus (data cut, August 1, 2021), 210,183 COVID-19-related publications included 720,801 unique authors, of which 360,005 authors had published at least 5 full papers in their career and 23,520 authors were at the top 2% of their scientific subfield based on a career-long composite citation indicator. The growth of COVID-19 authors was far more rapid and massive compared with cohorts of authors historically publishing on H1N1, Zika, Ebola, HIV/AIDS and tuberculosis. All 174 scientific subfields had some specialists who had published on COVID-19. In 109 of the 174 subfields of science, at least one in ten active, influential (top-2% composite citation indicator) authors in the subfield had authored something on COVID-19. 52 hyper-prolific authors had already at least 60 (and up to 227) COVID-19 publications each. Among the 300 authors with the highest composite citation indicator for their COVID-19 publications, most common countries were USA (n=67), China (n=52), UK (n=32), and Italy (n=18). The rapid and massive involvement of the scientific workforce in COVID-19-related work is unprecedented and creates opportunities and challenges. There is evidence for hyper-prolific productivity.

Denial of Service — Panel Discussion

The Decameron of poor research

<i>Most gracious readers, two boring researchers present a series of pitiful tales—covert and overt fraud, petty misdeeds, and misconceptions by honest and not so honest researchers, professors, industry sponsors, bureaucrats, and other legendary adventurers of modern science</i>

Error in Figure

Otavio Berwanger, MD, PhD; Eliana Vieira Santucci, RT; Pedro Gabriel Melo de Barros e Silva, MD, MHS, PhD; Isabella de Andrade Jesuíno, Pharm; Lucas Petri Damiani, MSc; Lilian Mazza Barbosa, RT; Renato Hideo Nakagawa Santos, Stat; Ligia Nasi Laranjeira, RT; Flávia de Mattos Egydio, BiolSc, MSc; Juliana Aparecida Borges de Oliveira, CN; Frederico Toledo Campo Dall Orto, MD; Pedro Beraldo de Andrade, MD, PhD; Igor Ribeiro de Castro Bienert, MD, PhD; Carlos Eduardo Bosso, MD; José Armando Mangione, MD, PhD; Carisi Anne Polanczyk, MD, PhD; Amanda Guerra de Moraes Rego Sousa, MD, PhD; Renato Abdala Karam Kalil, MD, PhD; Luciano de Moura Santos, MD; Andrei Carvalho Sposito, MD, PhD; Rafael Luiz Rech, MD, PhD; Antônio Carlos Sobral Sousa, MD, PhD; Felipe Baldissera, MD; Bruno Ramos Nascimento, MD, PhD; Roberto Rocha Corrêa Veiga Giraldez, MD, PhD; Alexandre Biasi Cavalcanti, MD, PhD; Sabrina Bernardez Pereira, MD, PhD; Luiz Alberto Mattos, MD, PhD; Luciana Vidal Armaganijan, MD, PhD; Hélio Penna Guimarães, MD, PhD; José Eduardo Moraes Rego Sousa, MD, PhD; John Hunter Alexander, MD, MHS; Christopher Bull Granger, MD; Renato Delascio Lopes, MD, MHS, PhD; for the SECURE-PCI Investigators

SRD5A2 gene polymorphisms and the risk of prostate cancer: a meta-analysis.

Several polymorphisms in the 5alpha-reductase type 2 (SRD5A2) gene have been implicated as risk factors for prostate cancer. We performed a meta-analysis of 9 studies (12 comparisons) with V89L genotyping (2558 prostate cancer cases and 3349 controls), 7 studies (8 comparisons) with A49T genotyping (1594 cases and 2137 controls), and 4 studies with TA repeat genotyping (1109 cases and 1378 controls). The random effects odds ratio (OR) for the L versus V allele was 1.02 [95% confidence interval (CI), 0.94-1.11]. There was no suggestion of an overall effect either in recessive or dominant modeling, and comparison of L/L versus V/V also showed no differential prostate cancer susceptibility (OR, 1.03; 95% CI, 0.83-1.28). The random effects OR for the T versus A allele was 1.56 (95% CI, 0.93-2.62). However, excluding the first published study there was no evidence for any effect (OR, 1.08; 95% CI, 0.72-1.61). Moreover, the T allele had a low prevalence (0%, 1%, and 2% in Asian, African and European controls, respectively). The random effects OR for longer versus short TA alleles was 0.88 (95% CI, 0.74-1.05). Longer TA allele homozygotes were nonsignificantly under-represented among prostate cancer cases (OR, 0.53; 95% CI, 0.26-1.06). We exclude a role for the V89L polymorphism in conferring susceptibility to prostate cancer. The A49T and TA repeat polymorphisms may have a modest effect on prostate cancer susceptibility, but bias and chance findings cannot be excluded; any genuine genetic effects would account only for a small proportion of prostate cancer in the population.

Reply to letter by Ferrante di Ruffano et al.: Patient outcomes in randomized comparisons of diagnostic tests are still the ultimate judge