A timeshared, runtime reconfigurable hardware co-processing architecture

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.Includes bibliographical references (leaves 73-74).The constant desire for increased performance in microprocessor systems has led to the need for specialized hardware cores to accelerate specific computational tasks. In this thesis, we explore the potential of using FPGA partial reconfiguration to create a platform for customized hardware cores that may be loaded on demand, at runtime, and replaced when not in use. We implement two new software tools, bitparse and bitrender, to demonstrate the bitstream relocation technique. Further, we present a functional microprocessor system coupled with a runtime reprogramable peripheral synthesized on a Xilinx Virtex-5 FPGA and discuss its performance implications.by Benjamin S. Gelb.M.Eng

Secondary magnetic inclusions in detrital zircons from the Jack Hills, Western Australia, and implications for the origin of the geodynamo

The time of origin of Earth’s dynamo is unknown. Detrital zircon crystals containing ferromagnetic inclusions from the Jack Hills of Western Australia have the potential to contain the oldest records of the geodynamo. It has recently been argued that magnetization in these zircons indicates that an active dynamo existed as far back as 4.2 Ga. However, the ages of ferromagnetic inclusions in the zircons are unknown. Here we present the first detailed characterization of the mineralogy and spatial distribution of ferromagnetic minerals in Jack Hills detrital zircons. We demonstrate that ferromagnetic minerals in most Jack Hills zircons are commonly located in cracks and on the zircons’ exteriors. Hematite is observed to dominate the magnetization of many zircons, while other zircons also contain significant quantities of magnetite and goethite. This indicates that the magnetization of most zircons is likely to be dominantly carried by secondary minerals that could be hundreds of millions to billions of years younger than the zircons’ crystallization ages. We conclude that the existence of the geodynamo prior to 3.5 Ga has yet to be established

Secondary magnetic inclusions in detrital zircons from the Jack Hills, Western Australia, and implications for the origin of the geodynamo

The time of origin of Earth’s dynamo is unknown. Detrital zircon crystals containing ferromagnetic inclusions from the Jack Hills of Western Australia have the potential to contain the oldest records of the geodynamo. It has recently been argued that magnetization in these zircons indicates that an active dynamo existed as far back as 4.2 Ga. However, the ages of ferromagnetic inclusions in the zircons are unknown. Here we present the first detailed characterization of the mineralogy and spatial distribution of ferromagnetic minerals in Jack Hills detrital zircons. We demonstrate that ferromagnetic minerals in most Jack Hills zircons are commonly located in cracks and on the zircons’ exteriors. Hematite is observed to dominate the magnetization of many zircons, while other zircons also contain significant quantities of magnetite and goethite. This indicates that the magnetization of most zircons is likely to be dominantly carried by secondary minerals that could be hundreds of millions to billions of years younger than the zircons’ crystallization ages. We conclude that the existence of the geodynamo prior to 3.5 Ga has yet to be establishe

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Cardiac Surgery Outcomes: A Case for Increased Screening and Treatment of Obstructive Sleep Apnea

BACKGROUND: Because of the limited published information on complications that obstructive sleep apnea (OSA) patients experience during and after cardiac surgery, we investigated OSA as a risk factor for postoperative outcomes. METHODS: This project used the Northern New England Cardiovascular Disease Study Group\u27s data collected between 2011 and 2017 based on The Society of Thoracic Surgeons Adult Cardiac Surgery Database Data Collections form. A retrospective analysis of 1555 patients with OSA and 10,450 patients without OSA across 5 medical centers undergoing isolated coronary artery bypass grafting, isolated valve surgery, and combined coronary artery bypass grafting valve surgery was conducted. We used 1:1 nearest-neighbor propensity score matching with no replacement to balance characteristics among patients with and without OSA. RESULTS: There was a statistically significant increased risk of postoperative pneumonia, increased length of total and postoperative stay, and time to initial extubation. Two outcomes trended toward significance: intra- and postoperative intraaortic balloon pump use. Outcomes that failed to show statistical significance were surgical site infection, atrial fibrillation, cerebrovascular accident, permanent pacemaker placement, and blood products given. A chart review conducted on a subset of the study cohort revealed that more than 40% of OSA patients did not receive continuous positive airway pressure or bilevel positive airway pressure therapy postoperatively during their hospitalization. CONCLUSIONS: Our study aligns with the literature in concluding that OSA has deleterious effects on postoperative outcomes of cardiac surgery patients. Further research to better stratify OSA patients by severity are still needed. Additionally heightened awareness of the need to screen, diagnose, and properly treat patients for OSA is needed

Comparative effectiveness of revascularization strategies for early coronary artery disease: A multicenter analysis

OBJECTIVES: The goal of this analysis was to examine the comparative effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention among patients aged less than 60 years. METHODS: We performed a multicenter, retrospective analysis of all cardiac revascularization procedures from 2005 to 2015 among 7 medical centers. Inclusion criteria were age less than 60 years and 70% stenosis or greater in 1 or more major coronary artery distribution. Exclusion criteria were left main 50% or greater, ST-elevation myocardial infarction, emergency status, and prior revascularization procedure. After applying inclusion and exclusion criteria, the final study cohort included 1945 patients who underwent cardiac surgery and 2938 patients who underwent percutaneous coronary intervention. The primary end point was all-cause mortality stratified by revascularization strategy. Secondary end points included stroke, repeat revascularization, and 30-day mortality. We used inverse probability weighting to balance differences among the groups. RESULTS: After adjustment, there was no significant difference in 30-day mortality (surgery: 0.8%; percutaneous coronary intervention: 0.7%, P = .86) for patients with multivessel disease. Patients undergoing surgery had a higher risk of stroke (1.3% [n = 25] vs 0.07% [n = 2], P \u3c .001). Overall, surgery was associated with superior 10-year survival compared with percutaneous coronary intervention (hazard ratio, 0.71; 95% confidence interval, 0.57-0.88; P = .002). Repeat procedures occurred in 13.4% (n = 270) of the surgery group and 36.4% (n = 1068) of the percutaneous coronary intervention group, with both groups mostly undergoing percutaneous coronary intervention as their second operation. Accounting for death as a competing risk, at 10 years, surgery resulted in a lower cumulative incidence of repeat revascularization compared with percutaneous coronary intervention (subdistribution hazard ratio, 0.34; 95% confidence interval, 0.28-0.40; P \u3c .001). CONCLUSIONS: Among patients aged less than 60 years with 2-vessel disease that includes the left anterior descending or 3-vessel coronary artery disease, surgery was associated with greater long-term survival and decreased risk of repeat revascularization

Comparative effectiveness of revascularization strategies for early coronary artery disease: A multicenter analysis

OBJECTIVES: The goal of this analysis was to examine the comparative effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention among patients aged less than 60 years. METHODS: We performed a multicenter, retrospective analysis of all cardiac revascularization procedures from 2005 to 2015 among 7 medical centers. Inclusion criteria were age less than 60 years and 70% stenosis or greater in 1 or more major coronary artery distribution. Exclusion criteria were left main 50% or greater, ST-elevation myocardial infarction, emergency status, and prior revascularization procedure. After applying inclusion and exclusion criteria, the final study cohort included 1945 patients who underwent cardiac surgery and 2938 patients who underwent percutaneous coronary intervention. The primary end point was all-cause mortality stratified by revascularization strategy. Secondary end points included stroke, repeat revascularization, and 30-day mortality. We used inverse probability weighting to balance differences among the groups. RESULTS: After adjustment, there was no significant difference in 30-day mortality (surgery: 0.8%; percutaneous coronary intervention: 0.7%, P = .86) for patients with multivessel disease. Patients undergoing surgery had a higher risk of stroke (1.3% [n = 25] vs 0.07% [n = 2], P \u3c .001). Overall, surgery was associated with superior 10-year survival compared with percutaneous coronary intervention (hazard ratio, 0.71; 95% confidence interval, 0.57-0.88; P = .002). Repeat procedures occurred in 13.4% (n = 270) of the surgery group and 36.4% (n = 1068) of the percutaneous coronary intervention group, with both groups mostly undergoing percutaneous coronary intervention as their second operation. Accounting for death as a competing risk, at 10 years, surgery resulted in a lower cumulative incidence of repeat revascularization compared with percutaneous coronary intervention (subdistribution hazard ratio, 0.34; 95% confidence interval, 0.28-0.40; P \u3c .001). CONCLUSIONS: Among patients aged less than 60 years with 2-vessel disease that includes the left anterior descending or 3-vessel coronary artery disease, surgery was associated with greater long-term survival and decreased risk of repeat revascularization