Temperature-transferable coarse-graining of ionic liquids with dual graph convolutional neural networks.

Computer simulations can provide mechanistic insight into ionic liquids (ILs) and predict the properties of experimentally unrealized ion combinations. However, ILs suffer from a particularly large disparity in the time scales of atomistic and ensemble motion. Coarse-grained models are therefore used in place of costly all-atom simulations, accessing longer time scales and larger systems. Nevertheless, constructing the many-body potential of mean force that defines the structure and dynamics of a coarse-grained system can be complicated and computationally intensive. Machine learning shows great promise for the linked challenges of dimensionality reduction and learning the potential of mean force. To improve the coarse-graining of ILs, we present a neural network model trained on all-atom classical molecular dynamics simulations. The potential of mean force is expressed as two jointly trained neural network interatomic potentials that learn the coupled short-range and many-body long range molecular interactions. These interatomic potentials treat temperature as an explicit input variable to capture its influence on the potential of mean force. The model reproduces structural quantities with high fidelity, outperforms the temperature-independent baseline at capturing dynamics, generalizes to unseen temperatures, and incurs low simulation cost.

The Role of Crosslinked Polyethylene in Reducing Aggregated Costs of Total Hip Arthroplasty in the United States.

BACKGROUND: Widespread adoption of crosslinked polyethylene for the acetabular articular surface for total hip arthroplasty has substantially reduced revision rates and dislocation rates. We aim to provide estimates of the resulting magnitude of the annual reduction in aggregated costs of total hip arthroplasty surgery in the United States. METHODS: After we obtained, from the literature, the contrasting mid-term rates of revisions and dislocations of total hip arthroplasty using conventional polyethylene vs those using crosslinked polyethylene, specifically from only registry studies and prospective, randomized controlled studies, we multiplied these incidence figures by the cost estimates of these failures to generate approximations of the cost savings in the United States from the use of crosslinked polyethylene. RESULTS: The estimates suggest that in the United States these savings might be one billion dollars per annual cohort over a 15-year duration. CONCLUSION: The use of crosslinked polyethylene has reduced substantially the overall costs of total hip arthroplasty surgery in the United States.

To reduce routine computed tomographic angiography for thoracic aortic injury assessment in level II blunt trauma patients using three mediastinal signs on the initial chest radiograph: a preliminary report.

PURPOSE: CTA is routinely ordered on level II blunt thoraco-abdominally injured patients for assessment of injury to the thoracic aorta. The vast majority of such assessments are negative. The question being asked is, Does the accurate interpretation of the three mediastinal signs permit reliable determination of which patients need CTA for aortic assessment? The purpose of this investigation was to evaluate the role of three specifically selected mediastinal anatomic signs on the initial supine chest radiograph (CXR) of adult level II blunt thoraco-abdominally injured patients for the presence or absence of a mediastinal hematoma. The presence of a mediastinal hematoma is typically used as an indicator for computed tomographic angiography (CTA). The three mediastinal signs are the right para-tracheal stripe (RPTS), left para-spinal line (LPSL), and the left apical extra-pleural area (LAPA). MATERIALS AND METHODS: The patient triage designation (level II trauma) was made by the attending physician at the time of admission. The initial CXR image and the CTA report of the 197 adult blunt level II thoraco-abdominally injured patients obtained on the day of admission were compared. The CXR of each of the 197 patients was independently assessed by each of four observers specifically for the status of the three mediastinal signs. Each observer was blinded to the CTA report until after the status of the three mediastinal sign evaluation had been determined. Two or three of the mediastinal signs being positive were required to determine that the CXR was positive for a mediastinal hematoma. RESULTS: Two or three of the selected mediastinal signs were normal in 192 (97.5%) patients. None of these patients had either a mediastinal hematoma or a major aortic injury on CTA. In each of the remaining five (2.5%) patients, two or three of the mediastinal signs were abnormal. Each of these patients had a mediastinal hematoma and a major thoracic aortic injury on CTA. CONCLUSIONS: This preliminary study suggests that the accurate interpretation of the three specifically selected mediastinal signs on the initial supine CXR of adult level II blunt thoraco-abdominally injured patients could reduce the need for routine CTA for thoracic aortic injury assessment, and requires verification by an additional study.

Edge loading has a paradoxical effect on wear in metal-on-polyethylene total hip arthroplasties.

BACKGROUND: Edge wear is an adverse factor that can negatively impact certain THAs. In some metal-on-metal THAs, it can lead to adverse tissue reactions including aseptic lymphocytic vasculitis-associated lesions and even to pseudotumor formation. In some ceramic-on-ceramic THAs, it can lead to squeaking and/or stripe wear. Edge wear in metal-on-metal and ceramic-on-ceramic THAs can also be associated with accelerated wear across the articulation of these joints. QUESTIONS/PURPOSES: I asked: Does edge wear occur in metal-on-polyethylene (MOP) articulations? And if so, does it increase joint wear? METHODS: I examined the evidence in the literature for edge wear occurring in MOP THA and then assessed the evidence in the literature for data supporting the concept that edge wear in MOP hips could accelerate wear across the articulation over time. RESULTS: Extensive data in the literature confirm edge wear is common in MOP THA. Surprisingly, the evidence does not support that it accelerates wear across the articulation. In fact, substantial data support the concept that it does not. CONCLUSIONS: These observations suggest, in terms of edge wear accelerating overall wear, MOP articulation may have a privileged position compared to hard-on-hard THA articulations.

ADD It Up: An Evaluation of Antibiotic Duration at Hospital Discharge at a Community Hospital.

BACKGROUND: According to the Centers for Disease Control and Prevention, patients admitted to the hospital are commonly discharged on antibiotic therapy with prolonged courses of therapy, which contributes to excessive antibiotic exposure and adverse events. The purpose of this study was to evaluate total antibiotic duration of therapy at hospital discharge at Indiana University Health Arnett, White Memorial, and Frankfort hospitals. METHODS: A multicenter, retrospective electronic health record review was conducted from 1 January to 30 June 2019. Patients were included if they were at least 18 years of age, began antibiotic therapy while admitted, and continued antibiotic therapy at hospital discharge for 1 of the following indications: skin/soft tissue infection (SSTI), urinary tract infection (UTI), community-acquired pneumonia (CAP), or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The number of days of therapy (DOT) of each inpatient and outpatient antibiotic prescribed was collected to calculate the total DOT, which was utilized to determine the appropriateness of the duration of therapy. RESULTS: Of the 547 patients included, 233 patients (42.6%) had CAP, 120 (21.9%) had UTI, 101 (18.5%) had SSTI, and 93 (17%) had AECOPD. The median duration of antibiotic therapy across all indications was 9 days (interquartile range [IQR], 7-11). Median duration for CAP was 9 days (IQR, 7-10), AECOPD was 7 days (IQR, 5-9), UTI was 8 days (IQR, 6-10), and SSTI was 12 days (IQR, 10-14). CONCLUSIONS: Excess antimicrobial duration at hospital discharge represents an unmet need of antimicrobial stewardship programs.

Active learning and neural network potentials accelerate molecular screening of ether-based solvate ionic liquids.

Solvate ionic liquids (SIL) have promising applications as electrolyte materials. Despite the broad design space of oligoether ligands, most reported SILs are based on simple tri- and tetraglyme. Here, we describe a computational search for complex ethers that can better stabilize SILs. Through active learning, a neural network interatomic potential is trained from density functional theory data. The learned potential fulfills two key requirements: transferability across composition space, and high speed and accuracy to find low-energy ligand-ion poses across configurational space. Candidate ether ligands for Li+, Mg2+ and Na+ SILs with higher binding affinity and electrochemical stability than the reference compounds are identified. Lastly, their properties are related to the geometry of the coordination sphere.

The first 50 years of total hip arthroplasty: lessons learned.

Fifty years have passed since the first total hip arthroplasty of the modern era was performed. At this, the vantage point, it is reasonable to review these five decades, inquiring behind the single dominating observation that, in its current form, this operation is one of the most successful of all surgical procedures for the management of end-stage human disease. What are the generic lessons that can be derived from the experience? Succinctly, five major observations appear valuable. They are "skunk works," "Pasteur's motto," "the totally unexpected," "research solutions," and "the role of alternatives." "Skunk works," an industrial management term, might be characterized as an innovative endeavor that is offline and off-budget resulting from the relentless pursuit of a vivid dream by creative zealots who eschew defeat. Pasteur's motto dealt with serendipity, which was crucial to total hip arthroplasty progress. The totally unexpected is represented by an entirely new manmade disease, "periprosthetic osteolysis." The research solutions are represented by the complex, sophisticated contemporary research that has unraveled periprosthetic osteolysis and suggested modes of correction. Finally, the application of "alternatives" has characterized major progress. Importantly, these, or similar generic observations, may provide insights into important progress in the future.

The correlation between minor or unrecognized developmental deformities and the development of osteoarthritis of the hip.

The 20th century brought three major conceptual changes about osteoarthritis of the hip. The first was a dramatic change in the understanding of the etiology of many cases of osteoarthritis of the hip. The second was the establishment of the mechanism by which minor developmental abnormalities lead to arthritis. The third was, for the first time, the possibility that the rate of disease development could be retarded and even possibly prevented from progressing. To understand these conceptual changes, it is essential to define the terms used to describe osteoarthritis of the hip.

Arthroplasty implant registries over the past five decades: Development, current, and future impact.

Local, regional, and national registries have played an important role in the development of hip and knee arthroplasty and the treatment of patients with various maladies of these joints. Four arthroplasty registries stand out as leading forces behind the drive to popularize the use of registries and pursue the concept of evidence based medicine. The Mayo registry, started by Mark Coventry, is recognized as the oldest continuing registry for arthroplasty. The Harris Registry at Massachusetts General Hospital, along with the Mayo Registry, has greatly contributed to the advancement of arthroplasty surgery and have served an important role of identifying poorly performing implants and techniques in the United States. The Swedish Knee Arthroplasty Registry is the oldest national registry dedicated to joint arthroplasty and along with the Swedish Hip Arthroplasty Registry have established the infrastructure, analysis and reporting mechanisms, and leadership that has enabled other countries to subsequently develop national registries around the world. As more countries have adopted the concept of national registries, a new area of research is possible by pooling the resources of large registries as is now occurring with the Nordic countries. Several international organizations have been formed to promote future collaboration and develop international standards. The process of globalization of registries is a result of continued efforts over the past 50 years in improving and disseminating the knowledge gained from the early registries. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2319-2330, 2018.

Contact stress assessment of conventional and highly crosslinked ultra high molecular weight polyethylene acetabular liners with finite element analysis and pressure sensitive film.

Stress magnitude and distribution of both conventional polyethylene versus a crosslinked polyethylene in the liner of a total hip replacement (THR) were examined using finite element analysis and pressure sensitive film. Both types of polyethylene were assessed against head sizes of 22 and 28 mm with 5-mm thick polyethylene liners and head sizes of 28, 38, and 46 mm with 3-mm thick polyethylene liners. Liners with 5-mm conventional polyethylene represented successful combinations with long track records. Our hypothesis was that although the combination of the large head and the lower modulus of the highly crosslinked polyethylene would lead to lower stresses, the stresses would be excessive if the liner was extremely thin at 3 mm. Von Mises stresses at the articulating surface of the highly crosslinked liners were lower, when compared to conventional polyethylene, in every THR size examined. Specifically, however, the 38- and 46-mm inner diameter (ID) highly crosslinked polyethylene even at the extreme of only 3-mm thick had lower stresses than the 22-mm ID conventional liner of 5-mm thickness. These data indicate that the use of a large head against highly crosslinked material even at 3-mm thickness results in lower stresses than in an existing conventional 22-mm head and 5-mm thick combination. Obviously, other considerations will influence the minimum thickness to be recommended.

The effect of real-time aging on the oxidation and wear of highly cross-linked UHMWPE acetabular liners.

Irradiation decreases the wear of ultra-high molecular weight polyethylene (UHMWPE) but generates residual free radicals, precursors to long-term oxidation. Melting or annealing is used in quenching free radicals. We hypothesized that irradiated and once-annealed UHMWPE would oxidize while irradiated and melted UHMWPE would not, and that the oxidation in the former would increase wear. Acetabular liners were real-time aged by immersion in an aqueous environment that closely mimicked the temperature and oxygen concentration of synovial fluid. After 95 weeks of real-time aging, once-annealed components were oxidized; the melted components were not. The wear rate of the real-time aged irradiated and once-annealed components was higher than the literature reported values of other contemporary highly cross-linked UHMWPEs. Single annealing after irradiation used with terminal gamma sterilization may adversely affect the long-term oxidative stability of UHMWPE components.

Primary cementless acetabular components in hips with severe developmental dysplasia or total dislocation. A concise follow-up, at an average of sixteen years, of a previous report.

UNLABELLED: We previously reported the seven-year results of the use of a hemispherical, porous-coated acetabular component in twenty consecutive primary total hip arthroplasties in a highly selected group, namely, patients with severe developmental dysplasia or total dislocation of the hip. The present report describes the outcomes of those hips nine years later, at an average follow-up of sixteen years (range, 11.5 to nineteen years). Since the time of our prior report, two shells were revised; one revision was done because of aseptic loosening and the other, because of polyethylene liner dissociation without tine fracture. The remaining shells were well fixed. No pelvic osteolysis was evident on plain radiographs. The average polyethylene liner wear rate was 0.09 mm/yr. With failure defined as aseptic loosening of the shell, the average sixteen-year survival for the shell was 92%. We believe that this cup had excellent fixation at a long duration of follow-up of sixteen years in this highly selected set of patients with difficult hip problems. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

High placement of noncemented acetabular components in revision total hip arthroplasty. A concise follow-up, at a minimum of fifteen years, of a previous report.

We previously reported the average ten-year results associated with the use of porous-coated noncemented acetabular shells that were placed at a high hip center at the time of revision total hip arthroplasty in thirty-four patients (thirty-six hips) with severe acetabular bone loss. We now report the average 16.8-year results for twenty-one patients (twenty-three hips). Of the original cohort of forty-four patients (forty-six hips), thirty-nine patients (forty-one hips; 89%) retained the shell. Two shells (4.3%) were revised because of aseptic loosening, and three (6.5%) were revised because of infection. Six femoral components were revised because of femoral osteolysis, and seven were revised because of aseptic loosening without osteolysis. On the basis of our results after an average duration of follow-up of 16.8 years, we believe that the placement of an uncemented acetabular component at a high hip center continues to be an excellent technique for revision total hip arthroplasty in selected patients with severe acetabular bone loss.

Revision of failed acetabular components with use of so-called jumbo noncemented components. A concise follow-up of a previous report.

Acetabular revision in the presence of major bone-stock deficiency is a difficult clinical and surgical problem. Of an original pool of twenty-four consecutive patients treated with an acetabular revision with a so-called jumbo (>65-mm) cementless hemispherical acetabular component, fifteen were followed for an average of seven years in our previous study. The current report presents the results for the twelve patients in this group who were alive at a minimum of twelve years (mean, 13.9 years) postoperatively and agreed to return for follow-up. The average final Harris hip score was 79 points. No acetabular shell had been revised because of aseptic loosening, and none was loose as seen radiographically. The complication rate was high but was largely related to infection. In the patients without infection, the fixation of these large sockets remained excellent at the time of long-term follow-up.

Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal.

The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals.