BioSimulators: a central registry of simulation engines and services for recommending specific tools.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.

Comparing Nasopharyngeal and Midturbinate Nasal Swab Testing for the Identification of Severe Acute Respiratory Syndrome Coronavirus 2.

Testing of paired midturbinate (MT) nasal and nasopharyngeal (NP) swabs, collected by trained personnel from 40 patients with coronavirus disease 2019 (COVID-19), showed that more NP (76/95 [80%]) than MT swabs tested positive (61/95 [64%]) (P = .02). Among samples collected a week after study enrollment, fewer MT than NP samples were positive (45% vs 76%; P = .001).

Reactive capture using metal looping: the effect of oxygen.

In the effort to create a sustainable future economy, the ability to directly convert dilute gas-phase CO2 in waste gas streams into useful products would be a valuable tool, which may be achievable using Grignard reagents as both the capture and the conversion materials. The magnesium salt by-product can be recovered, and metallic magnesium regenerated through conventional high-efficiency electrolysis. This stoichiometric approach is known as metal looping, where the magnesium acts as the energy vector for the capture and conversion, allowing both to occur at room temperature and atmospheric pressure. However, the process has only previously been demonstrated with 12% CO2 in nitrogen mixtures. If we consider this process in a real post-combustion flue gas conversion scenario, the sensitivity of Grignard reagents to other gases (and water vapour) must be considered. While some of these gases and the water vapour are relatively easily removed, in most flue gas streams the most common other gas present, oxygen, would be far more challenging to excise, and oxygen is known to react with Grignard reagents, albeit slowly. In order to determine if higher oxygen concentrations could be tolerated, allowing the possibility of a variety of relatively inexpensive and possibly profitable direct CO2 conversion pathways to be developed, a range of industrially relevant CO2/O2 mixtures were made and carefully bubbled through phenylmagnesium bromide solutions.

Early modified primary closure for treatment of cardiac implantable electronic device pocket infections.

BACKGROUND: Guidance for wound management of the vacated generator pocket in cardiac implantable electronic device (CIED) pocket infections after removal of all hardware and tissue debridement is limited. The typical surgical technique for management of a purulent wound is to allow healing by secondary intention. An alternative approach uses negative pressure wound therapy with or without delayed primary closure. While effective in managing infection, these approaches increase hospital length of stay and costs. We present our experience with a third option: modified early primary wound closure over a suction device. METHODS: All patients with CIED pocket infections who presented to our institution between September 2018 and October 2020 underwent extraction of hardware and modified primary wound closure over a negative pressure Jackson-Pratt drain. Length of hospital and postoperative stay, complications, and recurrent infections were recorded. RESULTS: During the study period, 14 patients underwent modified primary wound closure for CIED pocket infections. Mean length of hospital stay was 6.64 days ± 4.01 days (standard deviation [SD]). Mean postoperative length of stay was 3.92 ± 2.21 days (SD). Two patients (both on intravenous heparin for mechanical valve prostheses) required re-exploration for bleeding. No patients developed recurrent infection at a mean follow up of 363 ± 245 days (SD). CONCLUSION: Based on our experience, early modified primary wound closure for CIED pocket infections appears to be safe and allows for prompt discharge with no observed re-infections.

Racial and ethnic differences in left atrial appendage occlusion wait time, complications, and periprocedural management.

PURPOSE: Non-white patients are underrepresented in left atrial appendage occlusion (LAAO) trials, and racial disparities in LAAO periprocedural management are unknown. METHODS: We assessed sociodemographics and comorbidities of consecutive patients at our institution undergoing LAAO between 2015 and 2020, then in adjusted analyses, compared procedural wait time, procedural complications, and post-procedure oral anticoagulation (OAC) use in whites versus non-whites. RESULTS: Among 109 patients undergoing LAAO (45% white), whites had lower CHA2 DS2 VASc scores, on average, than non-whites (4.0 vs. 4.8, p = .006). There was no difference in median time from index event (IE) or initial outpatient cardiology encounter to LAAO procedure (whites 10.5 vs. non-whites 13.7 months, p = .9; 1.9 vs. 1.8 months, p = .6, respectively), and there was no difference in procedural complications (whites 4% vs. non-whites 5%, p = .33). After adjusting for CHA2 DS2 VASc score, OAC use at discharge tended to be higher in whites (OR 2.4, 95% CI [0.9-6.0], p = .07). When restricting the analysis to those with prior gastrointestinal (GI) bleed, adjusting for CHA2 DS2 VASc score and GI bleed severity, whites had a nearly five-fold odds of being discharged on OAC (OR 4.6, 95% CI [1-21.8], p = 0.05). The association between race and discharge OAC was not mediated through income category (total mediation effect 19% 95% CI [-.04-0.11], p = .38). CONCLUSION: Despite an increased prevalence of comorbidities amongst non-whites, wait time for LAAO and procedural complications were similar in whites versus non-whites. Among those with prior GI bleed, whites were nearly five-fold more likely to be discharged on OAC than non-whites, independent of income.

Effect of Chronic Domperidone Use on QT Interval: A Large Single Center Study.

GOALS: The goal of this study was to determine the effect and safety of domperidone on QTc interval at the commonly prescribed doses of 30 to 80 mg daily. BACKGROUND: Domperidone is a dopamine receptor antagonist used for the treatment of gastroparesis. However, it has been associated with QT prolongation, ventricular arrhythmias, and sudden cardiac death. STUDY: This study analyzed patients prescribed domperidone for treatment of gastroparesis between January 2012 and September 2017 at a single center. This study reviewed EKGs, primarily the QTc interval, taken at baseline, 2 to 6 months after initiation of domperidone, 6 to 12 months after initiation, and ≥12 months after initiation. Concurrent QTc prolonging medications were recorded for each patient. The primary endpoint was QTc prolongation >500 ms. Secondary endpoints were QTc >450 ms for males, a QTc>470 ms for females, QTc prolongation ≥20 ms above baseline, and QTc prolongation >60 ms above baseline. RESULTS: In total, 246 patients were included for analysis (age, 46.3±17.4 y; F 209). EKGs were available for all 246 patients before treatment, 170 patients at 2 to 6 months, 135 at 6 to 12 months, and 152 patients at least 1 year after domperidone initiation.Of 246 subjects, 15 patients (6.1%, 9 female) had clinically important QTc prolongation; 11 had QTc >450 ms for males or >470 ms for females; none had QTc prolongation >500 ms; 5 (2.0%) had >60 ms over baseline and 61 (24.7%) patients had QTc increase of ≥20 ms but <60 ms from baseline. CONCLUSIONS: Domperidone at the conventionally used doses to treat gastroparesis (30 to 80 mg/d) was associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant. These data suggest that domperidone can be safely prescribed at doses of 30 to 80 mg daily for the treatment of gastroparesis.

Temporal and spatial variability of instream indicator bacteria (Escherichia coli) and implications for water quality monitoring.

Many water quality monitoring programs quantify Escherichia coli, an indicator of fecal contamination and potential sewage pollution. However, interpretation of E. coli data can be complex due to abiotic factors that influence its growth and mortality. The goal of this study was to quantify the variability of E. coli in a river and assess the impact of that variability on water quality monitoring study design and sewage pollution source identification. Over 1900 samples were collected and analyzed from 2007 to 2017 in the Norwalk River in Connecticut. Sixty-six percent of the samples collected during weekly to monthly monitoring had E. coli concentrations below 200 CFU/100 mL, indicating that elevated bacteria concentrations were captured infrequently. Patterns observed during daily sampling indicated that the randomization of sampling days within a week may support the identification of pollution sources driven by human behavioral patterns. Spatial autocorrelation in bacteria concentrations was not observed between sites, indicating that the sample locations were not spaced sufficiently close together to be redundant for monitoring. On finer spatial scales however, detection of a known pollution source was found to be challenging at even short distances downstream, with less than 25% of the original source concentration detected at 10 m downstream and less than 10% by 1000 m downstream, suggesting that a high density of study sites may be needed to detect potential sources. These findings can be used to better understand the natural variability of this important indicator organism in freshwater systems, and inform more efficient and effective monitoring.

Association of Antitachycardia Pacing or Shocks With Survival in 69,000 Patients With an Implantable Defibrillator.

AIMS: Antitachycardia pacing (ATP) is an effective treatment for ventricular tachycardia (VT) and can reduce the frequency of shocks in patients with an implantable cardioverter defibrillator (ICD). The association between survival and ATP, as compared to a shock, has not been confirmed in a large patient population. This study aims to determine if patients with an ICD receiving ATP have lower mortality, as compared to those receiving shock. METHODS: Sixty-nine thousand three hundred and sixty-eight patients underwent ICD implantation between October 2008 and May 2013 and were enrolled in the remote monitoring network Merlin.net™ (St. Jude Medical, St. Paul, MN, USA). Patients were categorized into three groups based on the type of ICD therapy received during follow-up: no therapy (N = 47,927), ATP (N = 8,049), and shock (N = 13,392) groups. Survival was determined by linking implant records to the Social Security Death Index. RESULTS: The no therapy (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.56-0.64, P < 0.001) and ATP (HR 0.70, 95% CI 0.64-0.77, P < 0.001) groups were associated with a lower mortality risk than the shock group. These results were unaffected by age, gender, device type, atrial fibrillation (AF) burden, or ventricular rate. ATP was effective in 85% of episodes and ATP effectiveness was dependent on the ventricular rate. CONCLUSIONS: Mortality rates were higher in ICD patients who received only ATP compared to no therapy, but ICD patients who received a shock had higher mortality compared to both groups. Furthermore, the data suggest that age, gender, device type, AF burden, and rate of arrhythmia do not change the trend of higher mortality in patients receiving ICD shock compared to ATP alone.

Long-term arrhythmia follow-up of patients with myotonic dystrophy.

BACKGROUND: Myotonic dystrophy (MD) is the most common muscular dystrophy in adults and is associated with sudden death. Reported predictors of sudden death in this population include atrial tachyarrhythmias, a PR interval greater than 240 milliseconds, aberrant QRS conduction, and any degree of AV block. OBJECTIVE: We sought to report on the arrhythmic outcome of a cohort of patients with a new diagnosis of genetically proven MD. METHODS: We performed a retrospective review of 37 patients with genetically confirmed MD referred to our electrophysiology clinic for primary cardiac screening. RESULTS: There were 25 patients with MD type 1 (MD1) and 12 patients with MD type 2 (MD2). Eight patients with MD1 (32%) had atrial fibrillation, compared to only one patient with MD2 (8.3%). Patients with MD1 were more likely to have evidence of conduction disease abnormalities (40% vs. 8.3%, P = ns) and had a higher all-cause mortality (16% vs. 0%) than those with MD2. Criteria for recommending ICD implantation were based on sudden death risk factors suggested by published literature. Eleven patients were offered an ICD, 2 refused and died within the next year. Of the 9 patients who received an ICD, 8 had MD1. Three patients received appropriate shocks, 2 for monomorphic VT, and one for polymorphic VT. CONCLUSION: The presence of AV conduction disturbance in MD patients is associated with a greater risk for ventricular arrhythmias. MD1 was more likely to be associated with cardiac arrhythmias than MD2. The incidence of ventricular arrhythmias among those who received a primary prevention ICD was 33% over 22 months, with 2 patients experiencing monomorphic VT and one experiencing polymorphic VT.

Glove and gown effects on intraoperative bacterial contamination.

OBJECTIVE: Experiments were performed to determine the risk of bacterial contamination associated with changing outer gloves and using disposable spunlace paper versus reusable cloth gowns. BACKGROUND: Despite decades of research, there remains a lack of consensus regarding certain aspects of optimal aseptic technique including outer glove exchange while double-gloving and surgical gown type selection. METHODS: In an initial glove study, 102 surgical team members were randomized to exchange or retain outer gloves 1 hour into clean orthopedic procedures; cultures were obtained 15 minutes later from the palm of the surgeon's dominant gloved hand and from the surgical gown sleeve. Surgical gown type selection was recorded. A laboratory strike-through study investigating bacterial transmission through cloth and paper gowns was performed with coagulase-negative staphylococci. In a follow-up glove study, 251 surgical team members, all wearing paper gowns, were randomized as in the first glove study. RESULTS: Glove study 1 revealed 4-fold higher levels of baseline bacterial contamination (31% vs 7%) on the sleeve of surgical team members wearing cloth gowns than those using paper gowns [odds ratio (95% confidence interval): 4.64 (1.72-12.53); P = 0.0016]. The bacterial strike-through study revealed that 26 of 27 cloth gowns allowed bacterial transmission through the material compared with 0 of 27 paper gowns (P < 0.001). In glove study 2, surgeons retaining outer gloves 1 hour into the case had a subsequent positive glove contamination rate of 23% compared with 13% among surgeons exchanging their original outer glove [odds ratio (95% confidence interval): 1.97 (1.02-3.80); P = 0.0419]. CONCLUSIONS: Paper gowns demonstrated less bacterial transmission in the laboratory and lower rates of contamination in the operating room. Disposable paper gowns are recommended for all surgical cases, especially those involving implants, because of the heightened risk of infection. Outer glove exchange just before handling implant materials is also recommended to minimize intraoperative contamination.

Urea uptake and carbon fixation by marine pelagic bacteria and archaea during the Arctic summer and winter seasons.

How Arctic climate change might translate into alterations of biogeochemical cycles of carbon (C) and nitrogen (N) with respect to inorganic and organic N utilization is not well understood. This study combined 15N uptake rate measurements for ammonium, nitrate, and urea with 15N- and 13C-based DNA stable-isotope probing (SIP). The objective was to identify active bacterial and archeal plankton and their role in N and C uptake during the Arctic summer and winter seasons. We hypothesized that bacteria and archaea would successfully compete for nitrate and urea during the Arctic winter but not during the summer, when phytoplankton dominate the uptake of these nitrogen sources. Samples were collected at a coastal station near Barrow, AK, during August and January. During both seasons, ammonium uptake rates were greater than those for nitrate or urea, and nitrate uptake rates remained lower than those for ammonium or urea. SIP experiments indicated a strong seasonal shift of bacterial and archaeal N utilization from ammonium during the summer to urea during the winter but did not support a similar seasonal pattern of nitrate utilization. Analysis of 16S rRNA gene sequences obtained from each SIP fraction implicated marine group I Crenarchaeota (MGIC) as well as Betaproteobacteria, Firmicutes, SAR11, and SAR324 in N uptake from urea during the winter. Similarly, 13C SIP data suggested dark carbon fixation for MGIC, as well as for several proteobacterial lineages and the Firmicutes. These data are consistent with urea-fueled nitrification by polar archaea and bacteria, which may be advantageous under dark conditions.

Risk of stroke or transient ischemic attack after atrial fibrillation ablation with oral anticoagulant use guided by ECG monitoring and pulse assessment.

INTRODUCTION: We sought to gain insight into stroke risk after atrial fibrillation (AF) ablation. METHODS AND RESULTS: We followed 1,990 patients for >1 year (49 ± 29 months) who underwent AF ablation. Prior to stopping oral anticoagulants (OAC), we performed 3-week transtelephonic ECG monitoring (TTM) and taught patients heart rate and pulse assessment. Documented AF or inability to do monitoring or assess pulse precluded stopping OAC in CHADS2 ≥1 patients. OAC was stopped in 546/840 (65%) with CHADS2  = 0; 384/796 (48%) with CHADS2  = 1 and 101/354 (40%) with CHADS2 ≥ 2. Sixteen strokes or TIAs occurred (0.2%/patient-year); 5 in CHADS2  = 0 patients (all off OAC); 5 in CHADS2  = 1 (1 off and 4 on OAC); and 6 in CHADS2 ≥2 (2 off and 4 on OAC). Twelve of 16 patients (75%) with stroke or TIA had documented AF. In patients "off " OAC, stroke rate/year stratified by the CHADS2 score was similar (CHADS2  = 0: 0.28%; CHADS2  = 1: 0.07%; CHADS2 ≥2: 0.50%; P = NS). There was no difference in stroke risk "on" versus "off " OAC in CHADS2  = 1 (0.48% vs. 0.07%) or CHADS2 ≥2 (0.39% vs. 0.50%). Risk of major bleeding per patient year "on" OAC was > "off " OAC (13/1,138 (1.14%) versus 1/832 (0.1%); P<0.016). CONCLUSIONS: Post-AF ablation with OAC guided by TTM and pulse assessment: (1) Overall stroke or TIA rate risk is low and risk is due to recurrent AF and (2) OAC can be stopped in 40% of CHADS2 ≥2 patients with low stroke and hemorrhagic risk.

Unipolar voltage abnormality is associated with greater left ventricular dysfunction in ischemic cardiomyopathy.

INTRODUCTION: Following myocardial infarction (MI), left ventricular function is determined by cardiac remodeling occurring in both infarcted and noninfarcted myocardium (NIM). Unipolar voltage mapping may detect remodeling changes in NIM that are associated with the left ventricular ejection fraction (LVEF). We aimed to identify (1) unipolar voltage characteristics in patients with chronic MI, and (2) association of voltage abnormalities with degree of left ventricular dysfunction (LVD). METHODS AND RESULTS: Two groups of patients with ischemic cardiomyopathy (ICM) who underwent LV endocardial mapping during catheter ablation for ventricular tachycardia (VT) between January 2010 and December 2012 were studied. The first group (19 males) had mild to moderate LVD (M-LVD, LVEF >35%) and was matched for age, sex, infarction size, and infarction location with 10 males who had severe LVD (S-LVD, LVEF <35%). Both bipolar and unipolar endocardial abnormal voltage areas were measured and compared between groups. Abnormal bipolar area was comparable in both groups (30 ± 8% in the S-LVD group vs 28 ± 8% in the M-LVD group; P = 0.5). Total abnormal unipolar voltage area was significantly larger in the S-LVD group (57 ± 14% vs 43 ± 13%; P = 0.02). The abnormal unipolar voltage area within the normal bipolar voltage area was greater in the S-LVD group (26 ± 11% vs 15 ± 16%; P = 0.03). In receiver operating characteristic curve analysis, an 18.0% cut-off value for abnormal unipolar area within NIM identified severe LVD, with 90% sensitivity and 79% specificity (area under the curve 0.821). CONCLUSIONS: Patients with ICM and severe LVD have larger areas of unipolar voltage abnormality in the noninfarcted tissue than patients with M-LVD.

Same-day contralateral implantation of a permanent device after lead extraction for isolated pocket infection.

AIMS: The purpose of this study is to examine the safety and outcomes of same-day reimplantation at the contralateral pectoral site in patients with device extraction for pocket infection but with negative blood cultures and no signs of systemic infection. METHODS AND RESULTS: Clinical and procedure-related data were retrospectively collected on 15 (11 male, mean age 77) device-dependent patients who underwent device and complete lead extraction (mean 2.5 leads per patient, mean implant duration 6.2 years) for local pocket infection, and who had a new contralateral device implanted on the same day. Temporary pacing via the femoral vein was used during extraction. The infected pocket was managed with an elliptical skin incision, debridement, full capsule resection, and primary wound closure with the end of the wound left open for a Penrose drain. Intravenous antibiotics were used prior to and through the procedure, and continued for a mean of 2 days post-procedure, with oral antibiotics used thereafter for a mean course of 2 weeks. No infections of the new device system occurred, with a mean follow-up of 39.6 months (range 12-74 months). CONCLUSION: In the setting of device erosion and isolated pocket infection without systemic or bloodstream involvement, a new contralateral device may be implanted on the same day as pocket debridement and system extraction without developing infection of the new permanent hardware. This strategy can be useful in patients with pacemaker-dependence, as an alternative to using a temporary pacing system.

RV-only pacing can produce a Q wave in lead 1 and an R wave in V1: implications for biventricular pacing.

BACKGROUND: Biventricular (bi-v) pacing improves congestive heart failure and mortality in patients with left ventricular (LV) dysfunction and electrical dyssynchrony. Effective resynchronization must include an LV pacing contribution to the QRS. Leads 1 and V1 are often exclusively used to verify proper biventricular pacing. METHODS: In 40 patients referred to our cardiac resynchronization therapy (CRT) optimization clinic, 12-lead electrocardiograms (ECGs) were obtained during bi-v pacing, right ventricular (RV)-only pacing, LV-only pacing, and a range of atrio-ventricular and ventriculo-ventricular intervals. The presenting bi-v QRS morphology was compared to RV and LV pacing, and RV-only pacing was evaluated for the presence of a Q wave in lead 1 and an R wave in V1. RESULTS: In 22 patients (55%), RV pacing produced an initial Q wave in lead 1 and/or R wave in V1, mimicking bi-v pacing. In three patients, the presenting bi-v paced ECG looked identical to RV-only pacing. In 28 patients (70%), LV pacing was advanced by a mean of 30 ms after CRT optimization. Using all 12 ECG leads, especially the precordial leads, was necessary to appreciate the QRS changes that occurred when LV pacing meaningfully contributed to electrical activation. CONCLUSIONS: Because of LV pacing latency, some patients require an earlier LV offset to achieve proper resynchronization pacing. Commonly used ECG criteria cannot verify meaningful LV pacing contribution during biventricular pacing because RV-only pacing often creates a Q wave in lead 1 and/or R wave in V1. The full 12-lead ECG during biventricular pacing should be compared with isolated RV and LV pacing to verify that LV pacing is properly contributing to the QRS.

Inducibility of atrial fibrillation and flutter following pulmonary vein ablation.

INTRODUCTION: Prior reports demonstrate prognostic value in noninducibility of atrial arrhythmias after atrial fibrillation (AF) ablation and suggest their utility in guiding additional ablation lesion sets. The type and mechanism of induced atrial arrhythmias, their relationship to the underlying atrial substrate, and prognostic significance of induced organized atrial arrhythmias are unknown. METHODS AND RESULTS: One hundred forty-four patients (30 women; median age 60 years; 54% with paroxysmal AF) undergoing AF ablation (circumferential pulmonary vein isolation and focal ablation of nonvein triggers on isoproterenol) were evaluated prospectively. All underwent a standardized postablation induction protocol from the coronary sinus and right atrium: 15 beat burst pacing at 250 milliseconds and decrementing to 180 milliseconds. Sustained rhythms were defined as greater than 2 minutes Of 144 patients, 55 patients (38.2%) did not have sustained inducible arrhythmias. Fifty-two (36.1%) had inducible AF and 37 (25.7%) had inducible organized arrhythmias. A logistic regression analysis showed that age (OR 2.10 per decade; P = 0.003) and hypertension (OR 4.15; P = 0.009) were predictive of inducibility. However, inducibility of either AF or organized arrhythmias was not prognostic of clinical recurrence at 1 year postablation (P = 0.65). Furthermore, inducibility of organized arrhythmias did not predict clinical recurrence of an organized arrhythmia. Only LA size (OR 2.18; 95% CI 1.02-4.67; P = 0.04) and persistent AF (OR 2.43; 95% CI 1.09-5.40; P = 0.03) predicted atrial arrhythmia recurrence. CONCLUSIONS: Multisite atrial burst pacing post-AF ablation induced organized rhythms in 25.7% and AF in 36.1% of patients after AF ablation. Hypertension and age predict inducibility of arrhythmias, but inducibility did not predict clinical recurrence in follow-up. Distinguishing organized atrial arrhythmias from AF did not yield any further prognostic information. The utility of aggressive stimulation protocols after AF ablation for prognosis and to guide therapy appears limited.