Thermodynamic Computing

The hardware and software foundations laid in the first half of the 20th Century enabled the computing technologies that have transformed the world, but these foundations are now under siege. The current computing paradigm, which is the foundation of much of the current standards of living that we now enjoy, faces fundamental limitations that are evident from several perspectives. In terms of hardware, devices have become so small that we are struggling to eliminate the effects of thermodynamic fluctuations, which are unavoidable at the nanometer scale. In terms of software, our ability to imagine and program effective computational abstractions and implementations are clearly challenged in complex domains. In terms of systems, currently five percent of the power generated in the US is used to run computing systems - this astonishing figure is neither ecologically sustainable nor economically scalable. Economically, the cost of building next-generation semiconductor fabrication plants has soared past $10 billion. All of these difficulties - device scaling, software complexity, adaptability, energy consumption, and fabrication economics - indicate that the current computing paradigm has matured and that continued improvements along this path will be limited. If technological progress is to continue and corresponding social and economic benefits are to continue to accrue, computing must become much more capable, energy efficient, and affordable. We propose that progress in computing can continue under a united, physically grounded, computational paradigm centered on thermodynamics. Herein we propose a research agenda to extend these thermodynamic foundations into complex, non-equilibrium, self-organizing systems and apply them holistically to future computing systems that will harness nature's innate computational capacity. We call this type of computing "Thermodynamic Computing" or TC.Comment: A Computing Community Consortium (CCC) workshop report, 36 page

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

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