Publications

Comparative evaluation of memory models for chip multiprocessors

There are two competing models for the on-chip memory in Chip Multiprocessor (CMP) systems: hardware-managed coherent caches and software-managed streaming memory . This paper performs a direct comparison of the two models under the same set of assumptions about technology, area, and computational capabilities. The goal is to quantify how and when they differ in terms of performance, energy consumption, bandwidth requirements, and latency tolerance for general-purpose CMPs. We demonstrate that for data-parallel applications on systems with up to 16 cores, the cache-based and streaming models perform and scale equally well. For certain applications with little data reuse, streaming scales better due to better bandwidth use and macroscopic software prefetching. However, the introduction of techniques such as hardware prefetching and nonallocating stores to the cache-based model eliminates the streaming advantage. Overall, our results indicate that there is not sufficient advantage in building streaming memory systems where all on-chip memory structures are explicitly managed. On the other hand, we show that streaming at the programming model level is particularly beneficial, even with the cache-based model, as it enhances locality and creates opportunities for bandwidth optimizations. Moreover, we observe that stream programming is actually easier with the cache-based model because the hardware guarantees correct, best-effort execution even when the programmer cannot fully regularize an application's code.

Bipolar circuit elements providing self-completion-indication

An ordinary synchronous system uses clocks to determine data signal validity. To avoid the problems of distributing high-speed clocks and partitioning logic to fit within clock cycles, asynchronous circuit elements must provide their own completion indication using self-timing. Basic bipolar circuit elements which modify differential current-steering gate styles to achieve completion indication without increasing the number of wires between gate stages and with only about a 50% cost in transistor density per stage are proposed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Recommendations on data sharing in HIV drug resistance research

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

JAMA

Noise analysis of LSO-PSAPD PET detector front-end multiplexing circuits

We are designing a 1mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> resolution PET (Positron Emission Tomography) system with over twenty-thousand readout channels. Multiplexing of the PSAPD (position sensitive avalanche photodiode) detectors would simplify the readout electronics and reduce the density of the circuit board design. We used simulations and experiments to study the performance of three front-end circuit configurations, 1) no multiplexing, 2) multiplexing with single-ended preamplifiers, and 3) multiplexing with differential preamplifiers, by evaluating their energy resolution and crystal identification ability. With single-ended multiplexing, there is no degradation in energy resolution but there is some degradation in crystal identification. With the novel differential multiplexing scheme presented in this paper, in simulation, there is less than 0.1dB degradation in energy resolution and no significant degradation in crystal identification. We also present a pseudo-differential technique which can be used when differential preamplifiers are not available, which we found gives a slight improvement over single-ended multiplexing.

Rounding algorithms for IEEE multipliers

Several technology independent rounding algorithms for multiplying normalized numbers are presented. The first is a simple rounding algorithm suitable for software simulation or moderate performance hardware multipliers. The next two algorithms are parallel addition schemes suitable for high-performance VLSI multipliers. One of them eliminates the carry produced by the lower-order bits from the critical path. Several methods for computing the sticky bit are also presented. Included is a new fast and efficient technique for computing the sticky bit directly from the carry-save form without undergoing the expense of a carry-propagate addition.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Maternal Cell-Free Viremia in the Natural History of Perinatal HIV-1 Transmission

We performed a meta-analysis of the predictive value of maternal cell-free viral load in vertical HIV-1 transmission, including 9 cohorts with 1115 mother-infant pairs (696 untreated and 419 treated women). The pooled rate of transmission in untreated women was 21.3% (95% confidence interval [CI], 18.3%-24.5%). The rates of transmission for untreated women in the <1000 copies/ml, 1000 to 9999 copies/ml, and > or = 10,000 copies/ml categories were 5% (95% CI, 2%-11%), 15% (95% CI, 11%-20%) and 37% (95% CI, 29%-46% by random effects), respectively. The area under the receiver operating characteristic (ROC) curve in individual studies ranged from 0.67 to 1.00. The predictive performance of RNA differed between cohorts in which different percentages of transmitters had RNA values >10,000 copies/ml. When 95% of transmitters have RNA values >1000 copies/ml, 77% of nontransmitters would also have values above this cutoff. Transmission rates for treated women in the 1000 to 9999 copies/ml category (7%; 95% CI, 4%-11%,) and > or = 10,000 copies/ml category (18%; 95% CI, 12%-27%) were probably lower than those for untreated women, whereas the transmission rate for treated women with <1000 copies/ml was 5% (95% CI, 2%-11 %). Thus, the risk gradient between RNA categories seems attenuated in treated women. Several aspects of the design, analysis, and reporting of research in this area may be improved in the future with attention to selection and observer biases, multivariate adjustment, and technical consistency. Maternal HIV-1 RNA is a modest predictor of transmission for individual mothers, but a strong predictor of the average risk in groups of untreated mothers. Its discriminatory power is better in untreated than in treated populations and is better in cohorts with a high prevalence of elevated viral load values than in cohorts with generally low levels of viremia.

Table of Contents

Poor performance of clinical prediction models: the harm of commonly applied methods

Evaluation of Excess Statistical Significance in Meta-analyses of 98 Biomarker Associations with Cancer Risk

Most well-documented biomarkers of cancer risk without evidence of bias pertain to infectious agents. Conversely, an excess of statistically significant findings was observed in studies of IGF/insulin and inflammation systems, suggesting reporting biases.

Metformin and health outcomes: An umbrella review of systematic reviews with meta‐analyses

Abstract Background The objective was to capture the breadth of outcomes that have been associated with metformin use and to systematically assess the quality, strength and credibility of these associations using the umbrella review methodology. Methods Four major databases were searched until 31 May 2020. Meta‐analyses of observational studies and meta‐analyses of randomized controlled trials (RCTs) (including active and placebo control arms) were included. Results From 175 eligible publications, we identified 427 different meta‐analyses, including 167 meta‐analyses of observational studies, 147 meta‐analyses of RCTs for metformin vs placebo/no treatment and 113 meta‐analyses of RCTs for metformin vs active medications. There was no association classified as convincing or highly suggestive from meta‐analyses of observational studies, but some suggestive/weak associations of metformin use with a lower mortality risk of CVD and cancer. In meta‐analyses of RCTs, metformin was associated with a lower incidence of diabetes in people with prediabetes or no diabetes at baseline; lower ovarian hyperstimulation syndrome incidence (in women in controlled ovarian stimulation); higher success for clinical pregnancy rate in poly‐cystic ovary syndrome (PCOS); and significant reduction in body mass index in people with type 1 diabetes mellitus, in women who have obesity/overweight with PCOS and in obese/overweight women. Of 175 publications, 166 scored as low or critically low quality per AMSTAR 2 criteria. Conclusions Observational evidence on metformin seems largely unreliable. Randomized evidence shows benefits for preventing diabetes and in some gynaecological and obstetrical settings. However, almost all meta‐analyses are of low or critically low quality according to AMSTAR 2 criteria.

Adverse Events: The More You Search, the More You Find

Editorials21 February 2006Adverse Events: The More You Search, the More You FindJohn P.A. Ioannidis, MD, Cynthia D. Mulrow, MD, MSc, Deputy Editor, and Steven N. Goodman, MD, PhDJohn P.A. Ioannidis, MDFrom the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205., Cynthia D. Mulrow, MD, MSc, Deputy EditorFrom the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205., and Steven N. Goodman, MD, PhDFrom the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-4-200602210-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail People want reliable information about potential harms of medications. Concerns about possible adverse effects guide therapy selections, and unpleasant surprises about unsuspected harms cause anxiety and make headlines (1). We often rely on compendia and product inserts for information about such effects. These materials offer litanies of possible adverse events, sometimes accompanied by an estimate of how often those events might occur. From whence are these estimates derived? What do they really mean? How can we better measure and understand how many and what kinds of harms may be caused by medications?Sources of Evidence about Medication-Related HarmsWe can ...References1. Topol EJ. Failing the public health—rofecoxib, Merck, and the FDA. N Engl J Med. 2004;351:1707-9. [PMID: 15470193] CrossrefMedlineGoogle Scholar2. Kaufman DW, Shapiro S. Epidemiological assessment of drug-induced disease. Lancet. 2000;356:1339-43. [PMID: 11073036] CrossrefMedlineGoogle Scholar3. Papanikolaopu PN, Christidi G, Ioannidis JPA. Large-scale evidence on harms of medical interventions: randomized, controlled trials versus observational studies. CMAJ [In press]. Google Scholar4. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215-20. [PMID: 11980521] CrossrefMedlineGoogle Scholar5. Bent S, Padula A, Avins AL. Brief communication: better ways to question patients about adverse medical events. A randomized, controlled trial. Ann Intern Med. 2006;144:257-61. LinkGoogle Scholar6. Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337:725-33. [PMID: 9287227] CrossrefMedlineGoogle Scholar7. Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999;341:1865-73. [PMID: 10601505] CrossrefMedlineGoogle Scholar8. Götzsche PC. Non-steroidal anti-inflammatory drugs. BMJ. 2000;320:1058-61. [PMID: 10764369] CrossrefMedlineGoogle Scholar9. Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA. 2001;285:437-43. [PMID: 11242428] CrossrefMedlineGoogle Scholar10. Ioannidis JP, Evans SJ, Götzsche PC, O'Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781-8. [PMID: 15545678] LinkGoogle Scholar11. Jonville-Béra AP, Giraudeau B, Autret-Leca E. Reporting of drug tolerance in randomized clinical trials: when data conflict with authors' conclusions. Ann Intern Med. 2006;144:306-7. LinkGoogle Scholar12. Papanikolaou PN, Ioannidis JP. Availability of large-scale evidence on specific harms from systematic reviews of randomized trials. Am J Med. 2004;117:582-9. [PMID: 15465507] CrossrefMedlineGoogle Scholar13. Strand CV, Simon LS, Tugwell P, Brooks P, Boers M. OMERACT 7 International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials. Introduction. Accessed at jrheum.com/archives/oct05.html on 10 January 2006. Google Scholar14. Bonhoeffer J, Kohl K, Chen R, Duclos P, Heijbel H, Heininger U, et al. The Brighton Collaboration: addressing the need for standardized case definitions of adverse events following immunization (AEFI). Vaccine. 2002;21:298-302. [PMID: 12450705] CrossrefMedlineGoogle Scholar15. Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176-81. [PMID: 12903007] CrossrefMedlineGoogle Scholar16. Venning GR. Identification of adverse reactions to new drugs. II—How were 18 important adverse reactions discovered and with what delays? Br Med J (Clin Res Ed). 1983;286:289-92. [PMID: 6218859] CrossrefMedlineGoogle Scholar17. Centers for Education and Research on Therapeutics Risk Assessment Workshop. Risk assessment of drugs, biologics and therapeutic devices: present and future issues. Pharmacoepidemiol Drug Saf. 2003;12:653-62. [PMID: 14762981] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205.Disclosures: None disclosed.Corresponding Author: John P.A. Ioannidis, MD, Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece; e-mail, [email protected]uoi.gr.Current Author Addresses: Dr. Ioannidis: Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.Dr. Mulrow: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.Dr. Goodman: Division of Biostatistics, Johns Hopkins Sidney Kimmel Cancer Center, Suite 1103, 550 North Broadway, Baltimore, MD 21205. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBrief Communication: Better Ways To Question Patients about Adverse Medical Events Stephen Bent , Amy Padula , and Andrew L. Avins Reporting of Drug Tolerance in Randomized Clinical Trials: When Data Conflict with Authors' Conclusions Annie Pierre Jonville-Béra , Bruno Giraudeau , and Elisabeth Autret-Leca Metrics Cited byProne position for acute respiratory failure in adultsInterpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerationsCollecting dataSafety and risks of shiatsu: Protocol for a systematic reviewUnpleasant meditation-related experiences in regular meditators: Prevalence, predictors, and conceptual considerationsThe MethodsComparing Long-term Mortality After Carotid Endarterectomy vs Carotid Stenting Using a Novel Instrumental Variable Method for Risk Adjustment in Observational Time-to-Event DataThe reporting of harms in publications on randomized controlled trials funded by the "Programme Hospitalier de Recherche Clinique," a French academic funding schemeAdverse Events Following Cervical Disc Arthroplasty: A Systematic ReviewIdentifying Bias in Clinical Cancer ResearchWorking towards consensus on methods used to elicit participant-reported safety data in uncomplicated malaria clinical drug studies: a Delphi technique studyHyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviewsAdverse Event Reporting in Clinical Trials of Intravenous and Invasive Pain Treatments: An ACTTION Systematic ReviewAdverse Effects of Psychotropic MedicationsVariation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documentsReporting of adverse events and statistical details of efficacy estimates in randomized clinical trials of pain in temporomandibular disordersUnwirksamkeit, Schaden und nicht intendierte Folgen der Implementierung von InterventionenIntroductionSafety monitoringAdverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic reviewSunitinib adverse events in metastatic renal cell carcinoma: a meta-analysisHow experiences become data: the process of eliciting adverse event, medical history and concomitant medication reports in antimalarial and antiretroviral interaction trialsComparison of Pooled Risk Estimates for Adverse Effects from Different Observational Study Designs: Methodological OverviewAdverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendationsOpen Issues in Intelligent Personal Health Record – An Updated Status Report for 2012Adverse event reporting in randomised controlled trials of neuropathic pain: Considerations for future practiceThiazolidinedione use and cancer incidence in type 2 diabetes: A systematic review and meta-analysisAdherence to CONSORT harms-reporting recommendations in publications of recent analgesic clinical trials: An ACTTION systematic reviewAnalysis of the three United States Food and Drug Administration investigational device exemption cervical arthroplasty trialsSafety and Tolerability of Varenicline Tartrate (Champix ® /Chantix ® ) for Smoking Cessation in HIV-Infected Subjects: A Pilot Open-Label StudyReal-life versus package insert: A post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellersDifferent Black Box Warning Labeling for Same-Class DrugsMeta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological OverviewPublikationsbias in Studien jenseits RCTSources of information on adverse effects: a systematic reviewMonitoring self-reported adverse events: A prospective, pilot study in a UK osteopathic teaching clinicWhy Most Discovered True Associations Are InflatedEvaluation of Early and Late Toxicities in Chemoradiation TrialsTAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology GroupStopping at Nothing? Some Dilemmas of Data Monitoring in Clinical TrialsSteven N. Goodman, MD, MHS, PhDThe safety of etanercept for the treatment of plaque psoriasisAdverse-event rates: journals versus databasesAntimicrobial-Associated QT Interval Prolongation: Pointes of InterestCurrent awareness: Pharmacoepidemiology and drug safetyHypothyroidism Associated with Quetiapine Therapy; Paradoxical Bronchospasm Associated with Albuterol; Alcohol Cravings with Paroxetine Therapy?; Lamotrigine-Induced Toxic Epidermal Necrolysis – Three Cases; Acute Lung Injury with Vinorelbine; Adverse Events Related to Epinephrine Use in Asthma Patients Seen in the Emergency Department; Collecting Information from Patients Having Adverse Events; New Anticonvulsants – New Adverse EffectsRecent Publications on Medications and PharmacySystemic Therapy for Breast Cancer: Using Toxicity Data to Inform Decisions 21 February 2006Volume 144, Issue 4Page: 298-300KeywordsAdverse eventsAdverse reactionsClinical epidemiologyClinical trialsDrugsEvidence based medicineObservational studiesToxicity ePublished: 21 February 2006 Issue Published: 21 February 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. 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Management of Posterior Urethral Valves on the Basis of Urodynamic Findings

Abnormal urodynamic findings are common in boys with a history of posterior urethral valves. However, to our knowledge there are few reports on the results of treating these abnormal findings. We analyzed the treatment of abnormal urodynamic parameters and its outcome in 21 boys who underwent valve ablation.After valve ablation multichannel urodynamic studies were performed in 31 boys, including 21 in whom studies were done before and after therapy was started for abnormal parameters. Detrusor instability and impaired bladder compliance were treated with anticholinergics or augmentation cystoplasty, and impaired detrusor contractility was managed with clean intermittent catheterization.Before therapy 17 of 21 boys had impaired compliance and detrusor instability, 2 had impaired compliance without instability and 2 had instability alone. After treatment 8 boys had impaired compliance and 4 had detrusor instability. After anticholinergics were initiated new onset myogenic failure in 2 boys necessitated clean intermittent catheterization. Of the 13 patients who presented with urinary incontinence 10 became dry and 3 had improvement with therapy. Vesicoureteral reflux in 10 boys at the time of the initial urodynamic study resolved in 7 with anticholinergic medication and in 1 after clean intermittent catheterization was begun for severely impaired compliance. All 21 boys were treated with anticholinergics and 2 were ultimately treated with augmentation cystoplasty. Clean intermittent catheterization was also instituted in 5 patients, including the 2 who required clean intermittent catheterization after myogenic failure developed. Five boys with high voiding pressures were found to have outlet obstruction due to residual valve tissue in 2, bladder neck obstruction in 2 and urethral stricture in 1 despite normal flow rates in 2.Urodynamic studies are helpful in guiding therapy in boys after valve ablation. Anticholinergic therapy can improve compliance, decrease detrusor instability, improve continence and eliminate vesicoureteral reflux in the majority of boys, although there is an associated risk of myogenic failure. Flow rates and fluoroscopic voiding studies are often unable to detect outlet obstruction and must be obtained in conjunction with voiding pressure measurements to make this diagnosis.

JAMA

Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19

Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

Robust Energy-Efficient Adder Topologies

In this paper we explore the relationship between adder topology and energy efficiency. We compare the energy-delay tradeoff curves of selected 32- bit adder topologies, to determine how architectural features and design techniques affect energy efficiency. Optimizing different adders for the supply and threshold voltages, and transistor sizing, we show that topologies with the least number of logic stages having an average fanin of two per stage, and fewest wires are most energy efficient. While a design with fully custom sizes can be extremely tedious to layout, we show that custom sizing can be used as a guide to group different gates in the design, resulting in a manageable layout overhead without significant loss of energy efficiency.

Diet, body size, physical activity and risk of prostate cancer: An umbrella review of the evidence

Identification and evaluation of risk of generalizability biases in pilot versus efficacy/effectiveness trials: a systematic review and meta-analysis

Managing wire scaling: a circuit perspective

We update prior wire scaling studies with data from the 2001 and 2002 ITRS roadmaps, extending out to the 13 nm node. Combining this data with more sophisticated wire models, over nine generations we see both local and global wires degrading relative to gates, by one and three orders of magnitude respectively. However, using repeaters for global wires as well as for the relatively few long local wires improves them significantly and makes local wires track gate delays. Inductive effects for delay are negligible, and inductive noise, given relatively lowcost design heuristics, is insignificant compared to capacitive noise. Wire aspect ratio sets capacitive coupling, and is limited to 2.2 in the ITRS roadmap to limit this noise. However, at this ratio designers already need to employ a number of noise countermeasures, whose effectiveness imply that noise need no longer be a principal reason to limit wire aspect ratios.