Lessons learned in a decade of research software engineering gpu applications

After years of using Graphics Processing Units (GPUs) to accelerate scientific applications in fields as varied as tomography, computer vision, climate modeling, digital forensics, geospatial databases, particle physics, radio astronomy, and localization microscopy, we noticed a number of technical, socio-technical, and non-technical challenges that Research Software Engineers (RSEs) may run into. While some of these challenges, such as managing different programming languages within a project, or having to deal with different memory spaces, are common to all software projects involving GPUs, others are more typical of scientific software projects. Among these challenges we include changing resolutions or scales, maintaining an application over time and making it sustainable, and evaluating both the obtained results and the achieved performance

The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function

Objectives: We evaluated the effect of renal function on clinical failure rates of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in primary care. Methods: Data were retrospectively obtained from 78 Dutch general practitioner (GP) practices between 2013 and 2019. Eligible episodes in patients (>11 years) were those requiring 5 days of nitrofurantoin (NF5), single-dose fosfomycin–trometamol (FT1), 3 days of trimethoprim (TMP3) for uncomplicated cystitis, or 7 days of nitrofurantoin (NF7) or trimethoprim (TMP7) for complicated cystitis. Clinical failure was defined as second antibiotic prescription for cystitis or pyelonephritis within 28 days post-prescription. Mixed effects regression analysis was used, with patient and GP practice as random effects and demography, comorbidity, and cystitis history as fixed effects. Results: Adjusted odds ratios (aORs) for clinical failure per 10mL/min decrease in estimated glomerular filtration rate (eGFR) were 1.05 (95% CI: 1.01–1.09) for NF5 (n = 24,591), 0.96 (95% CI: 0.92–1.01) for FT1 (n = 5359), 0.98 (95% CI: 0.89–1.08) for TMP3 (n = 1064), 1.05 (95% CI: 1.02–1.09) for NF7 (n = 10,628) and 1.02 (95% CI: 0.93–1.14) for TMP7 (n = 831). In uncomplicated cystitis and eGFR ≥60 mL/min, clinical failures occurred in 14.6% (1895/12 980) of NF5-treated, 20.7% (266/1283) of FT1-treated (aOR versus NF5 1.37, 95% CI 1.18–1.59) and 20.8% (66/318) of TMP3-treated patients (aOR 1.42, 95% CI 1.07–1.87 versus NF5). In uncomplicated cystitis and eGFR <60 mL/min, FT1 resulted in 16.0% (39/244) and NF5 in 23.3% clinical failures (110/472), aOR: 0.61, 95% CI: 0.39–0.95). Conclusions: In eGFR ≥60 mL/min treatment with fosfomycin or trimethoprim for uncomplicated cystitis was associated with more clinical failure than treatment with nitrofurantoin, while in eGFR <60 mL/min nitrofurantoin was associated with more clinical failure than fosfomycin–trometamol. Renal function, if known, should be considered in the clinical decision-making for cystitis treatment

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not nor malized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk

Square root singularity in the viscosity of neutral colloidal suspensions at large frequencies

The asymptotic frequency $\omega$, dependence of the dynamic viscosity of neutral hard sphere colloidal suspensions is shown to be of the form $\eta_0 A(\phi) (\omega \tau_P)^{-1/2}$, where $A(\phi)$ has been determined as a function of the volume fraction $\phi$, for all concentrations in the fluid range, $\eta_0$ is the solvent viscosity and $\tau_P$ the P\'{e}clet time. For a soft potential it is shown that, to leading order steepness, the asymptotic behavior is the same as that for the hard sphere potential and a condition for the cross-over behavior to $1/\omega \tau_P$ is given. Our result for the hard sphere potential generalizes a result of Cichocki and Felderhof obtained at low concentrations and agrees well with the experiments of van der Werff et al, if the usual Stokes-Einstein diffusion coefficient $D_0$ in the Smoluchowski operator is consistently replaced by the short-time self diffusion coefficient $D_s(\phi)$ for non-dilute colloidal suspensions.Comment: 18 pages LaTeX, 1 postscript figur

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales

[Background] The possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections.[Methods] In 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points.[Results] 4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non–3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75–.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient.[Conclusions] A prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.J. R.-B. receives funds for research from Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund “A Way to Achieve Europe,” Operative Program Intelligent Growth 2014-2020.Peer reviewe

Novel clinical applications of state-of-the-art multi-slice computed tomography

Recent years have witnessed a rapid development of multi-slice computed tomography (MSCT) technology. The number of detector rows has increased from 4-slices to the current availability of 64-slice and even 320-slice systems. In addition, images are acquired with thinner slices and faster rotation times resulting in substantially improved image quality and diagnostic accuracy. Simultaneously, effective dose reduction acquisition techniques have been developed allowing considerable reduction of the radiation dose. Conceivably, these advancements may allow further expansion of the use of MSCT beyond the visual assessment of the presence or absence of significant coronary artery disease. Indeed, a particular advantage of the technique is that in addition to evaluation of the coronary arteries it also allows assessment of cardiac structures and function. The purpose of the current review is to discuss several novel applications of cardiac MSCT, including stenosis quantification, atherosclerotic plaque imaging and prognostification as well as imaging of left ventricular function, aortic and mitral valve anatomy using state-of-the-art technology

Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial):design and rationale of a nationwide stepped-wedge cluster-randomized trial

Background: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. Methods: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90 days after pancreatic resection. Discussion: It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice. Trial registration: Netherlands Trial Register: NL 6671. Registered on 16 December 2017

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study

Publisher Copyright: © 2022 The Author(s)Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.Peer reviewe