Design of robust scheduling methodologies for high performance computing

Scientific applications are often large, complex, computationally-intensive, and irregular. Loops are often an abundant source of parallelism in scientific applications. Due to the ever-increasing computational needs of scientific applications, high performance computing (HPC) systems have become larger and more complex, offering increased parallelism at multiple hardware levels. Load imbalance, caused by irregular computational load per task and unpredictable computing system characteristics (system variability), often degrades the performance of applications. Besides, perturbations, such as reduced computing power, network latency availability, or failures, can severely impact the performance of the applications. System variability and perturbations are only expected to increase in future extreme-scale computing systems. Extrapolating the current failure rate to Exascale would result in a failure every 20 minutes. Such failure rate and perturbations would render the computing systems unusable. This doctoral thesis improves the performance of computationally-intensive scientific applications on HPC systems via robust load balancing. Robust scheduling ensures and maintains improved load balanced execution under unpredictable application and system characteristics. A number of dynamic loop self-scheduling (DLS) techniques have been introduced and successfully used in scientific applications between the 1980s and 2000s. These DLS techniques are not fault-tolerant as they were originally introduced. In this thesis, we identify three major research questions to achieve robust scheduling (1) How to ensure that the DLS techniques employed in scientific applications today adhere to their original design goals and specifications? (2) How to select a DLS technique that will achieve improved performance under perturbations? (3) How to tolerate perturbations during execution and maintain a load balanced execution on HPC systems? To answer the first question, we reproduced the original experiments that introduced the DLS techniques to verify their present implementation. Simulation is used to reproduce experiments on systems from the past. Realistic simulation induces a similar analysis and conclusions to the analysis of the native results. To this end, we devised an approach for bridging the native and simulative executions of parallel applications on HPC systems. This simulation approach is used to reproduce scheduling experiments on past and present systems to verify the implementation of DLS techniques. Given the multiple levels of parallelism offered by the present HPC systems, we analyzed the load imbalance in scientific applications, from computer vision, astrophysics, and mathematical kernels, at both thread and process levels. This analysis revealed a significant interplay between thread level and process level load balancing. We found that dynamic load balancing at the thread level propagates to the process level and vice versa. However, the best application performance is only achieved by two-level dynamic load balancing. Next, we examined the performance of applications under perturbations. We found that the most robust DLS technique does not deliver the best performance under various perturbations. The most efficient DLS technique changes by changing the application, the system, or perturbations during execution. This signifies the algorithm selection problem in the DLS. We leveraged realistic simulations to address the algorithm selection problem of scheduling under perturbations via a simulation assisted approach (SimAS), which answers the second question. SimAS dynamically selects DLS techniques that improve the performance depending on the application, system, and perturbations during the execution. To answer the third question, we introduced a robust dynamic load balancing (rDLB) approach for the robust self-scheduling of scientific applications under failures (question 3). rDLB proactively reschedules already allocated tasks and requires no detection of perturbations. rDLB tolerates up to P −1 processor failures (P is the number of processors allocated to the application) and boosts the flexibility of applications against nonfatal perturbations, such as reduced availability of resources. This thesis is the first to provide insights into the interplay between thread and process level dynamic load balancing in scientific applications. Verified DLS techniques, SimAS, and rDLB are integrated into an MPI-based dynamic load balancing library (DLS4LB), which supports thirteen DLS techniques, for robust dynamic load balancing of scientific applications on HPC systems. Using the methods devised in this thesis, we improved the performance of scientific applications by up to 21% via two-level dynamic load balancing. Under perturbations, we enhanced their performance by a factor of 7 and their flexibility by a factor of 30. This thesis opens up the horizons into understanding the interplay of load balancing between various levels of software parallelism and lays the ground for robust multilevel scheduling for the upcoming Exascale HPC systems and beyond

Effects of surface chemical modifications on the adhesion of metallic interfaces. An high-throughput analysis

Chemical interactions between two surfaces in contact play a crucial role in determining the mechanical and tribological behavior of solid interfaces. These interactions can be quantified via adhesion energy, that is a measure of the strength by which two surfaces bind together. Several works in literature report how the presence of chemisorbed atoms at homo- and heterogeneous solid-solid interfaces drastically change their proprieties. A precise evaluation of how different species at solid contacts modulates their adhesion would be extremely beneficial for a range of different technological fields: from metallurgy to nuclear fusion. In this work we have used and high-throughput approach to systematically explore the effects of the presence of non-metallic elements, at different concentrations, on the adsorption and adhesion energies of different homogeneous metallic interfaces. Together with the databases for the adsorption and the adhesion energies, we calculated several other properties such as the charge transferred at the interface, the d-band edge shift for the substrate the Bond order and the interfacial density redistribution for the hundreds of systems analyzed. These values were used to define different trends with respect to chemical and concentration parameters that could be useful for the development of engineered interfaces with selected properties. In particular we noticed how the substrate with low filling of d-band are the most prone to adsorb ad-atoms and how the adsorption of almost all non-metallic elements decreases the adhesion energy of solid interfaces, particularly in the case of Fluorine. Carbon and Boron were the only two ad-atoms species that showed an opposite trend increasing the adhesion energy instead

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Synthesis and activity evaluation of short antifreeze peptides of type I shorthorn sculpin antifreeze protein

Organisms living in cold environments are adapted to tolerate the freezing cold conditions and survive at subzero temperature by evolving antifreeze proteins (AFPs). AFPs bind to ice crystals and inhibit ice crystals growth and change their morphology. AFPs have function to depress the freezing point in non-colligative manner, resulting in a difference between the freezing point and the melting point of these organisms’ aqueous fluids, a property known as thermal hysteresis (TH). They are also capable of inhibiting ice recrystallization in the frozen state. This phenomenon called ice recrystallization inhibition (IRI). The main aim of this study is to synthesize short antifreeze peptides from shorthorn sculpin antifreeze protein and analyze the functional properties of these peptides. The analysis of the antifreeze activity of the short peptides was studied in order to investigate the role of each segment in the overall antifreeze activity of shorthorn sculpin AFP. The peptides were designed based on shortening the parent peptide into three fragments which represent different regions of shorthorn sculpin AFP. The synthesis of these peptides was performed following solid phase peptide synthesis method. The antifreeze activity of each peptide was determined experimentally by performing TH and IRI activity assay. The secondary structure of the short antifreeze peptides was determined by circular dichroism spectroscopy. Using solid phase peptide synthesis method yielded peptides with at least 68% purity. Antifreeze activity assay revealed that the three peptide fragments were devoid of TH activity. Peptides SC1 and SC2 demonstrated moderate IRI and ice structuring morphology activities, while SC3 showed no activity. Secondary structure analysis indicated that the helical content was reduced with increasing temperature. The results indicated that there is no correlation between the helical content and antifreeze activity of the short peptides. As a conclusion, synthesizing short peptide fragments based on shortening shorthorn sculpin antifreeze protein (SS3) would results in short peptide segments that behave as ice modifiers rather than efficient ice inhibitors or true antifreeze peptides