MILEPOST GCC: machine learning based research compiler

International audienceTuning hardwired compiler optimizations for rapidly evolving hardware makes porting an optimizing compiler for each new platform extremely challenging. Our radical approach is to develop a modular, extensible, self-optimizing compiler that automatically learns the best optimization heuristics based on the behavior of the platform. In this paper we describe MILEPOST GCC, a machine-learning-based compiler that automatically adjusts its optimization heuristics to improve the execution time, code size, or compilation time of specific programs on different architectures. Our preliminary experimental results show that it is possible to considerably reduce execution time of the MiBench benchmark suite on a range of platforms entirely automatically

The long-time dynamics of two hydrodynamically-coupled swimming cells

Swimming micro-organisms such as bacteria or spermatozoa are typically found in dense suspensions, and exhibit collective modes of locomotion qualitatively different from that displayed by isolated cells. In the dilute limit where fluid-mediated interactions can be treated rigorously, the long-time hydrodynamics of a collection of cells result from interactions with many other cells, and as such typically eludes an analytical approach. Here we consider the only case where such problem can be treated rigorously analytically, namely when the cells have spatially confined trajectories, such as the spermatozoa of some marine invertebrates. We consider two spherical cells swimming, when isolated, with arbitrary circular trajectories, and derive the long-time kinematics of their relative locomotion. We show that in the dilute limit where the cells are much further away than their size, and the size of their circular motion, a separation of time scale occurs between a fast (intrinsic) swimming time, and a slow time where hydrodynamic interactions lead to change in the relative position and orientation of the swimmers. We perform a multiple-scale analysis and derive the effective dynamical system - of dimension two - describing the long-time behavior of the pair of cells. We show that the system displays one type of equilibrium, and two types of rotational equilibrium, all of which are found to be unstable. A detailed mathematical analysis of the dynamical systems further allows us to show that only two cell-cell behaviors are possible in the limit of $t\to\infty$, either the cells are attracted to each other (possibly monotonically), or they are repelled (possibly monotonically as well), which we confirm with numerical computations

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

Differential diagnosis of illness in travelers arriving from sierra Leone, Liberia, or guinea: A cross-sectional study from the Geosentinel surveillance network

Background: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. Objective: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. Design: Descriptive, using GeoSentinel records. Setting: 57 travel or tropical medicine clinics in 25 countries. Patients: 805 ill returned travelers and new mmigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. Measurements: Frequencies of demographic and travelrelated characteristics and illnesses reported. Results: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non–P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n= 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. Limitation: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. Conclusion: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality

Mepivacaine versus Bupivacaine Spinal Anesthesia for Early Postoperative Ambulation.

BACKGROUND: Early ambulation after total hip arthroplasty predicts early discharge. Spinal anesthesia is preferred by many practices but can delay ambulation, especially with bupivacaine. Mepivacaine, an intermediate-acting local anesthetic, could enable earlier ambulation than bupivacaine. This study was designed to test the hypothesis that patients who received mepivacaine would ambulate earlier than those who received hyperbaric or isobaric bupivacaine for primary total hip arthroplasty. METHODS: This randomized controlled trial included American Society of Anesthesiologists Physical Status I to III patients undergoing primary total hip arthroplasty. The patients were randomized 1:1:1 to 52.5 mg of mepivacaine, 11.25 mg of hyperbaric bupivacaine, or 12.5 mg of isobaric bupivacaine for spinal anesthesia. The primary outcome was ambulation between 3 and 3.5 h. Secondary outcomes included return of motor and sensory function, postoperative pain, opioid consumption, transient neurologic symptoms, urinary retention, intraoperative hypotension, intraoperative muscle tension, same-day discharge, length of stay, and 30-day readmissions. RESULTS: Of 154 patients, 50 received mepivacaine, 53 received hyperbaric bupivacaine, and 51 received isobaric bupivacaine. Patient characteristics were similar among groups. For ambulation at 3 to 3.5 h, 35 of 50 (70.0%) of patients met this endpoint in the mepivacaine group, followed by 20 of 53 (37.7%) in the hyperbaric bupivacaine group, and 9 of 51 (17.6%) in the isobaric bupivacaine group (P \u3c 0.001). Return of motor function occurred earlier with mepivacaine. Pain and opioid consumption were higher for mepivacaine patients in the early postoperative period only. For ambulatory status, 23 of 50 (46.0%) of mepivacaine, 13 of 53 (24.5%) of hyperbaric bupivacaine, and 11 of 51 (21.5%) of isobaric bupivacaine patients had same-day discharge (P = 0.014). Length of stay was shortest in mepivacaine patients. There were no differences in transient neurologic symptoms, urinary retention, hypotension, muscle tension, or dizziness. CONCLUSIONS: Mepivacaine patients ambulated earlier and were more likely to be discharged the same day than both hyperbaric bupivacaine and isobaric bupivacaine patients. Mepivacaine could be beneficial for outpatient total hip arthroplasty candidates if spinal is the preferred anesthesia type

The Customary International Law Game

Structural realists in political science and some rationalist legal scholars argue that customary international law cannot affect state behavior: that it is “epiphenomenal.” This article develops a game theoretic model of a multilateral prisoner’s dilemma in the customary international law context that shows that it is plausible that states would comply with customary international law under certain circumstances. Our model shows that these circumstances relate to: (i) the relative value of cooperation versus defection, (ii) the number of states effectively involved, (iii) the extent to which increasing the number of states involved increases the value of cooperation or the detriments of defection, including whether the particular issue has characteristics of a commons problem, a public good, or a network good, (iv) the information available to the states involved regarding compliance and defection, (v) the relative patience of states in valuing the benefits of long-term cooperation compared to short-term defection, (vi) the expected duration of interaction, (vii) the frequency of interaction, and (viii) whether there are also bilateral relationships or other multilateral relationships between the involved states. This model shows that customary international law is plausible in the sense that it may well affect state behavior where certain conditions are met. It shows what types of contexts, including malleable institutional features, may affect the ability of states to produce and comply with customary international law. This article identifies a number of empirical strategies that may be used to test the model

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases

Blood Leukocyte Dna Methylation Predicts Risk of Future Myocardial infarction and Coronary Heart Disease

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD