•Model-free control, staging and sequencing of VRF with multiple outdoor units.•ESC integrated staging and sequencing logic of outdoor-unit compressors and coils.•Stage off least-efficient compressor ...found by extremum seeking under reducing load.•Mode switching of least-efficient outdoor-unit coil found by extremum seeking.•Simulation validation with Modelica model of a VRF with multiple outdoor units.
This paper presents a model-free control and automatic staging strategy for the operation of a variable refrigerant flow system with multiple outdoor units, which maximizes energy efficiency in real time and handles the outdoor-unit operation during load changes. An extremum seeking controller is used to minimize the total power consumption in real time while the thermal load is regulated with inner loop controllers. Minimization of power with extremum seeking control leads naturally to manipulated input behavior that can be utilized to develop control logic for two aspects of multi-outdoor-unit operation in model-free manner: (1) automatically stage off the outdoor unit with least efficient compressor, and (2) automatically switch the operation of outdoor-unit heat exchanger between the evaporating and condensing mode for simultaneous heating and cooling. As the extremum seeking controller can drive the least-efficient compressor to a lower capacity, the outdoor unit with the least efficient compressor can thus be identified and turned off in a model-free manner under a decreasing load. Under simultaneous heating and cooling operation, the fan speed of the least efficient outdoor-unit heat exchanger will be lower than all other outdoor units, which indicates that the heat exchanger can be switched between operation as a condenser and evaporator to achieve thermal balance for higher efficiency. The proposed strategy is evaluated using a Modelica model of a variable-refrigerant-flow system that consists of three outdoor units and 12 indoor units. The effectiveness of the proposed framework is validated with the simulation study.
Background
Formulating sophisticated fluid therapy plans can be complicated and time consuming. Consequently, veterinarians in the field who lack experience, time, or confidence may formulate ...suboptimal fluid therapy plans.
Objectives
Compare conventional and app‐guided fluid therapy plans for simulated cases of neonatal calf diarrhea.
Participants
Third and fourth year veterinary students (n = 55) from The University of Sydney.
Methods
We developed a web app to assist fluid therapy formulation (http://calfaid.com) that was evaluated in a randomized case simulation trial. Participants were instructed to perform fluid therapy calculations and formulate an integrated fluid therapy plan for case scenarios using conventional methods and using the fluid therapy app. Responses were scored by a blinded study investigator using an a priori scoring guide and groups (conventional vs. app‐guided) were compared using linear mixed models.
Results
On average, total scores for app‐guided fluid therapy calculations were 20.6% points higher (95% confidence interval CI, 14.1‐27.1) than calculations completed using the conventional method (88.2% vs. 67.5%, respectively). On average, total scores for app‐guided integrated fluid therapy plans were 14.2% points higher (95% CI, 6.3‐22.2; 65.8% vs. 51.2%). Eighty percent of respondents indicated they would prefer to use the app‐guided method over the conventional method.
Conclusion and Clinical Importance
Our findings suggest that fluid therapy plans can be improved using apps.
Environmental exposures may have greater predictive power for type 2 diabetes than polygenic scores (PGS). Studies examining environmental risk factors, however, have included only individuals with ...European ancestry, limiting the applicability of results. We conducted an exposome-wide association study in the multiancestry Personalized Environment and Genes Study to assess the effects of environmental factors on type 2 diabetes.
Using logistic regression for single-exposure analysis, we identified exposures associated with type 2 diabetes, adjusting for age, BMI, household income, and self-reported sex and race. To compare cumulative genetic and environmental effects, we computed an overall clinical score (OCS) as a weighted sum of BMI and prediabetes, hypertension, and high cholesterol status and a polyexposure score (PXS) as a weighted sum of 13 environmental variables. Using UK Biobank data, we developed a multiancestry PGS and calculated it for participants.
We found 76 significant associations with type 2 diabetes, including novel associations of asbestos and coal dust exposure. OCS, PXS, and PGS were significantly associated with type 2 diabetes. PXS had moderate power to determine associations, with larger effect size and greater power and reclassification improvement than PGS. For all scores, the results differed by race.
Our findings in a multiancestry cohort elucidate how type 2 diabetes odds can be attributed to clinical, genetic, and environmental factors and emphasize the need for exposome data in disease-risk association studies. Race-based differences in predictive scores highlight the need for genetic and exposome-wide studies in diverse populations.
Image omitted - see PDF Methods The current PVI model integrates multiple data streams into an overall score derived from 12 key indicators—including well-established, general vulnerability factors ...for public health, plus emerging factors relevant to the pandemic—distributed across four domains: current infection rates, baseline population concentration, current interventions, and health and environmental vulnerabilities. Data sources in the current model (version 11.2.1) include the Social Vulnerability Index (SVI) of the Centers for Disease Control and Prevention (CDC) for emergency response and hazard mitigation planning (Horney et al. 2017), testing rates from the COVID Tracking Project (Atlantic Monthly Group 2020), social distancing metrics from mobile device data ( https://www.unacast.com/covid19/social-distancing-scoreboard), and dynamic measures of disease spread and case numbers ( https://usafacts.org/issues/coronavirus/). Acknowledgments We thank the information technology and web services staff at the National Institute of Environmental Health Sciences (NIEHS)/National Institutes of Health (NIH) for their help and support, as well as J.K. Cetina and D.J. Reif for their useful technical input and advice.
To support antimicrobial stewardship in livestock production, there is a growing array of point of care diagnostics to guide antimicrobial treatment. The primary objective of this observational study ...was to evaluate the diagnostic performance of 5 point of care tests currently available in Australia for guiding lactational treatment of non-severe clinical mastitis. A secondary objective was to describe the pathogen profiles of mastitis-causing organisms in cows managed in barns (“intensive”) and on pasture (“non-intensive”). Foremilk samples (n = 641) were collected by farm staff in dairy herds in Australia (n = 30) and tested at a university laboratory using a reference test and 5 index tests. The reference test was aerobic culture on Trypticase Soy Agar with 5% sheep blood followed by MALDI-TOF for identification of isolates. The following point of care tests were evaluated as index tests: Accumast®, biplate, Check-Up, Mastatest®, and 3M Petrifilm. We found that 23% of samples were contaminated, with the median herd contamination prevalence being 22%. After excluding contaminated samples, the most common diagnoses (according to the reference test) in intensive herds were no growth (31.7%), Klebsiella spp. (28.1%), E. coli (15.0%), and Strep. uberis (8.4%). The most common diagnoses in non-contaminated samples from cows in non-intensive herds were Strep. uberis (35.0%), no growth (26.9%), and E. coli (13.3%). After 24 h of incubation, all index tests demonstrated limited diagnostic sensitivity for identification of pathogens of interest (range: 0.06 to 0.63). Diagnostic performance was better at the group-level, with sensitivity and specificity for identification of non-contaminated gram-positive growths (i.e., cases that are widely considered to be candidates for antimicrobial treatment) being 0.84 and 0.75 (biplate), 0.76 and 0.90 (Accumast), 0.89 and 0.79 (Check-Up), 0.67 and 0.83 (Petrifilm), and 0.55 and 0.81 (Mastatest). In intensive herds, 22.7 to 40% of cases were classified as antimicrobial treatment candidates by index tests, which was less than for cows in non-intensive herds (41.3 to 61.0%). Despite limited diagnostic reliability at genus and species level, and the need to ensure samples are collected aseptically, our findings indicate that implementation of selective treatment protocols using the tests evaluated in this study would likely reduce antimicrobial usage in Australian herds.
Contrast-induced acute kidney injury (AKI) is a common and severe complication of percutaneous coronary intervention (PCI). Despite its substantial burden, contemporary data on the incremental costs ...of AKI are lacking. We designed this large, nationally representative study to examine: (1) the independent, incremental costs associated with AKI after PCI and (2) to identify the departmental components of cost contributing to the incremental costs associated with AKI. In this observational cross-sectional study from the Premier database, we analyzed 1,443,297 PCI patients at 518 US hospitals from 1/2006 to 12/2015. Incremental cost of AKI from a hospital perspective obtained by a microcosting approach, was estimated using mixed-effects, multivariable linear regression with hospitals as random effects. Costs were inflation-corrected to 2016 US$. AKI occurred in 82,683 (5.73%) of the PCI patients. Those with AKI had higher hospitalization cost than those without ($38,869, SD 42,583 vs $17,167 SD 13,994, p <0.001). After adjustment, the incremental cost associated with an AKI was $9,448 (95% confidence interval $9,338 to $9,558, p <0.001). AKI was also independently associated with an incremental length of stay of 3.6 days (p <0.001). Room and board costs were the largest driver of AKI costs ($4,841). Extrapolated to the United States, our findings imply an annual AKI cost burden of 411.3 million US$. In conclusion, in this national study of PCI patients, AKI was common and independently associated with ∼$10,000 incremental costs, implying a substantial burden of AKI costs in US hospitals. Successful efforts to prevent AKI in patients who underwent PCI could result in meaningful cost savings.
Coronary chronic total occlusions (CTOs) are commonly encountered complex lesions identified in 15% of all patients referred for coronary angiography. Chronic total occlusion remains the most ...powerful predictor of referral for coronary bypass surgery. The benefits of CTO percutaneous coronary intervention (PCI) include symptom relief, improved left ventricular function, and potentially a survival advantage associated with success when compared with failed CTO-PCI. Data from the NCDR (National Cardiovascular Data Registry) suggest that CTO-PCI attempt rates in the U.S. have not changed over the past 5 years despite significant advances in techniques and technology, some of which we review here. Additionally, these data highlight a major disparity in attempt rates based on operator PCI volume. Remaining barriers to attempting CTO-PCI in the U.S. include operator inexperience, the perception of increased risk of CTO-PCI, and financial disincentives to operators and hospitals. To overcome operator inexperience, participation in CTO clubs, the invitation of guest operators, and a dedicated CTO day can be implemented at institutions committed to learning advanced CTO-PCI techniques so that operators can overcome the barriers and offer patients access to percutaneous therapy when it is clinically indicated.
The aim of this study was to examine the independent impact of various care pathways, including those involving transradial intervention (TRI) and same-day discharge (SDD) after elective percutaneous ...coronary intervention (PCI), on hospital costs.
PCI is associated with costs of $10 billion annually. Alternative payment models for PCI are being implemented, but few data exist on strategies to reduce costs. Various PCI care pathways, including TRI and SDD, exist, but their association with costs and outcomes is unknown.
In total, 279,987 PCI patients eligible for SDD in the National Cardiovascular Data Registry CathPCI Registry linked to Medicare claims files were analyzed. Hospital costs in 2014 U.S. dollars were estimated using cost-to-charge ratios. Propensity scores for TRI and SDD, with propensity adjustment via inverse probability weighting, was performed.
Of the 279,987 PCI procedures, TRI was used in 9.0% (13.5% of which were SDD), and SDD was used in 5.3% of cases (23.1% of which were TRI). TRI (vs. transfemoral intervention) was associated with lower adjusted costs of $916 (95% confidence interval CI: $778 to $1,035), as was SDD ($3,502; 95% CI: $3,486 to $3,902). The adjusted cost associated with TRI and SDD was $13,389 (95% CI: $13,161 to $13,607), while the cost associated with transfemoral intervention and non-same-day discharge was $17,076 (95% CI: $16,999 to $17,147), a difference of $3,689 (95% CI: $3,486 to $3,902; p < 0.0001). Shifting current practice from transfemoral intervention non-same-day discharge to TRI SDD by 30% could potentially save a hospital performing 1,000 PCIs each year $1 million and the country $300 million annually.
Among Medicare beneficiaries, TRI with SDD was independently associated with fewer complications and lower in-hospital costs. These findings have important implications for changing the current PCI care pathways to improve outcomes and reduce costs.
Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) ...is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.
Abstract
Hazard evaluation of substances of “unknown or variable composition, complex reaction products and biological materials” (UVCBs) remains a major challenge in regulatory science because their ...chemical composition is difficult to ascertain. Petroleum substances are representative UVCBs and human cell-based data have been previously used to substantiate their groupings for regulatory submissions. We hypothesized that a combination of phenotypic and transcriptomic data could be integrated to make decisions as to selection of group-representative worst-case petroleum UVCBs for subsequent toxicity evaluation in vivo. We used data obtained from 141 substances from 16 manufacturing categories previously tested in 6 human cell types (induced pluripotent stem cell iPSC-derived hepatocytes, cardiomyocytes, neurons, and endothelial cells, and MCF7 and A375 cell lines). Benchmark doses for gene-substance combinations were calculated, and both transcriptomic and phenotype-derived points of departure (PODs) were obtained. Correlation analysis and machine learning were used to assess associations between phenotypic and transcriptional PODs and to determine the most informative cell types and assays, thus representing a cost-effective integrated testing strategy. We found that 2 cell types—iPSC-derived-hepatocytes and -cardiomyocytes—contributed the most informative and protective PODs and may be used to inform selection of representative petroleum UVCBs for further toxicity evaluation in vivo. Overall, although the use of new approach methodologies to prioritize UVCBs has not been widely adopted, our study proposes a tiered testing strategy based on iPSC-derived hepatocytes and cardiomyocytes to inform selection of representative worst-case petroleum UVCBs from each manufacturing category for further toxicity evaluation in vivo.
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