The characteristics and predictors of mortality in periprosthetic fractures around the knee.

Aims: Periprosthetic fractures (PPFs) around the knee are challenging injuries. This study aims to describe the characteristics of knee PPFs and the impact of patient demographics, fracture types, and management modalities on in-hospital mortality. Methods: Using a multicentre study design, independent of registry data, we included adult patients sustaining a PPF around a knee arthroplasty between 1 January 2010 and 31 December 2019. Univariate, then multivariable, logistic regression analyses were performed to study the impact of patient, fracture, and treatment on mortality. Results: Out of a total of 1,667 patients in the PPF study database, 420 patients were included. The in-hospital mortality rate was 6.4%. Multivariable analyses suggested that American Society of Anesthesiologists (ASA) grade, history of peripheral vascular disease (PVD), history of rheumatic disease, fracture around a loose implant, and cerebrovascular accident (CVA) during hospital stay were each independently associated with mortality. Each point increase in ASA grade independently correlated with a four-fold greater mortality risk (odds ratio (OR) 4.1 (95% confidence interval (CI) 1.19 to 14.06); p = 0.026). Patients with PVD have a nine-fold increase in mortality risk (OR 9.1 (95% CI 1.25 to 66.47); p = 0.030) and patients with rheumatic disease have a 6.8-fold increase in mortality risk (OR 6.8 (95% CI 1.32 to 34.68); p = 0.022). Patients with a fracture around a loose implant (Unified Classification System (UCS) B2) have a 20-fold increase in mortality, compared to UCS A1 (OR 20.9 (95% CI 1.61 to 271.38); p = 0.020). Mode of management was not a significant predictor of mortality. Patients managed with revision arthroplasty had a significantly longer length of stay (median 16 days; p = 0.029) and higher rates of return to theatre, compared to patients treated nonoperatively or with fixation. Conclusion: The mortality rate in PPFs around the knee is similar to that for native distal femur and neck of femur fragility fractures. Patients with certain modifiable risk factors should be optimized. A national PPF database and standardized management guidelines are currently required to understand these complex injuries and to improve patient outcomes.

CyVerse: Cyberinfrastructure for open science.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

Effects of Segregation on the Catalytic Properties of AgAuCuPdPt High-Entropy Alloy for CO Reduction Reaction.

Multicomponent alloys are promising catalysts for diverse chemical conversions, owing to the ability to tune their vast compositional space to maximize catalytic activity and product selectivity. However, elemental segregation, whereby the surface or grain boundaries of the material are enriched in a few elements, is a physically observed phenomenon in such alloys. Such segregation alters not only the composition but also the kinds of catalytically active sites present at the surface. Thus, elemental segregation, which can be achieved via various processing techniques, can be used as an additional knob in searching for alloy compositions that are both active and selective for a target chemical conversion. We demonstrate this using molecular simulations, machine learning, and Bayesian optimization to search for both random solid solution and "segregated" AgAuCuPdPt alloy compositions that are potentially active and selective for CO reduction reaction (CORR). Finally, we validate our findings by computing the reaction-free energy landscape for the CORR on the optimal alloy compositions via density functional theory calculations.

Predictors of mortality in periprosthetic fractures of the hip: Results from the national PPF study.

INTRODUCTION: Periprosthetic fractures (PPFs) around the hip joint are increasing in prevalence. In this collaborative study, we aimed to investigate the impact of patient demographics, fracture characteristics, and modes of management on in-hospital mortality of PPFs involving the hip. METHODS: Using a multi-centre cohort study design, we retrospectively identified adults presenting with a PPF around the hip over a 10-year period. Univariate and multivariable logistic regression analyses were performed to study the independent correlation between patient, fracture, and treatment factors on mortality. RESULTS: A total of 1,109 patients were included. The in-hospital mortality rate was 5.3%. Multivariable analyses suggested that age, male sex, abbreviated mental test score (AMTS), pneumonia, renal failure, history of peripheral vascular disease (PVD) and deep surgical site infection were each independently associated with mortality. Each yearly increase in age independently correlates with a 7% increase in mortality (OR 1.07, p=0.019). The odds of mortality was 2.99 times higher for patients diagnosed with pneumonia during their hospital stay [OR 2.99 (95% CI 1.07-8.37) p=0.037], and 7.25 times higher for patients that developed renal failure during their stay [OR 7.25 (95% CI 1.85-28.47) p=0.005]. Patients with history of PVD have a six-fold greater mortality risk (OR 6.06, p=0.003). Mode of treatment was not a significant predictor of mortality. CONCLUSION: The in-hospital mortality rate of PPFs around the hip exceeds 5%. The fracture subtype and mode of management are not independent predictors of mortality, while patient factors such as age, AMTS, history of PVD, pneumonia, and renal failure can independently predict mortality. Peri-operative optimisation of modifiable risk factors such as lung and kidney function in patients with PPFs around the hip during their hospital stay is of utmost importance.

Systematic Identification of Atom-Centered Symmetry Functions for the Development of Neural Network Potentials.

Neural network potentials are emerging as promising classical force fields that can enable long-time and large-length scale simulations at close to ab initio accuracies. They learn the underlying potential energy surface by mapping the Cartesian coordinates of atoms to system energies using elemental neural networks. To ensure invariance with respect to system translation, rotation, and atom index permutations, in the Behler-Parrinnello type of neural network potential (BP-NNP), the Cartesian coordinates of atoms are transformed into "structural fingerprints" using atom-centered symmetry functions (ACSFs). Development of an accurate BP-NNP for any chemical system critically relies on the choice of these ACSFs. In this work, we have proposed a systematic framework for the identification of an optimal set of ACSFs for any target system, which not only considers the diverse atomic environments present in the training dataset but also inter-ACSF correlations. Our method is applicable to different kinds of ACSFs and across diverse chemical systems. We demonstrate this by building accurate BP-NNPs for water and Cu2S systems.

Constant community identification in million-scale networks.

The inherently stochastic nature of community detection in real-world complex networks poses an important challenge in assessing the accuracy of the results. In order to eliminate the algorithmic and implementation artifacts, it is necessary to identify the groups of vertices that are always clustered together, independent of the community detection algorithm used. Such groups of vertices are called constant communities. Current approaches for finding constant communities are very expensive and do not scale to large networks. In this paper, we use binary edge classification to find constant communities. The key idea is to classify edges based on whether they form a constant community or not. We present two methods for edge classification. The first is a GCN-based semi-supervised approach that we term Line-GCN. The second is an unsupervised approach based on image thresholding methods. Neither of these methods requires explicit detection of communities and can thus scale to very large networks of the order of millions of vertices. Both of our semi-supervised and unsupervised results on real-world graphs demonstrate that the constant communities obtained by our method have higher F1-scores and comparable or higher NMI scores than other state-of-the-art baseline methods for constant community detection. While the training step of Line-GCN can be expensive, the unsupervised algorithm is 10 times faster than the baseline methods. For larger networks, the baseline methods cannot complete, whereas all of our algorithms can find constant communities in a reasonable amount of time. Finally, we also demonstrate that our methods are robust under noisy conditions. We use three different, well-studied noise models to add noise to the networks and show that our results are mostly stable.

Chronic tophaceous gout mimicking widespread metastasis.

Gout is a common crystal-induced arthropathy affecting mainly the joints of the appendicular skeleton; however, rarely this condition affects the axial skeleton as well. Spinal gout can cause radiculopathy, cord compression, canal stenosis and discitis. We describe a case of a 71-year-old woman where the initial presentation of destructive arthropathy and spinal masses secondary to axial gout was mistaken for a metastatic malignancy. Despite chronic polyarthropathy and bilateral subcutaneous gouty tophi, spinal gout was not considered a differential diagnosis during initial assessment.The patient was managed conservatively with pharmacological treatment resulting in improvement of her upper limb radiculopathy and systemic joint pain, although little improvement in mobility. Such extensive involvement is rare and the masses can mimic an underlying metastatic disease. Careful history and clinical examination recognising polyarthropathy and subcutaneous tophi can aid the clinician to make the right diagnosis and institute correct treatment. Delay in recognising gout as a differential diagnosis can lead to marked morbidity as illustrated in our case.

Automated data abstraction for quality surveillance and outcome assessment in radiation oncology.

Rigorous radiotherapy quality surveillance and comprehensive outcome assessment require electronic capture and automatic abstraction of clinical, radiation treatment planning, and delivery data. We present the design and implementation framework of an integrated data abstraction, aggregation, and storage, curation, and analytics software: the Health Information Gateway and Exchange (HINGE), which collates data for cancer patients receiving radiotherapy. The HINGE software abstracts structured DICOM-RT data from the treatment planning system (TPS), treatment data from the treatment management system (TMS), and clinical data from the electronic health records (EHRs). HINGE software has disease site-specific "Smart" templates that facilitate the entry of relevant clinical information by physicians and clinical staff in a discrete manner as part of the routine clinical documentation. Radiotherapy data abstracted from these disparate sources and the smart templates are processed for quality and outcome assessment. The predictive data analyses are done on using well-defined clinical and dosimetry quality measures defined by disease site experts in radiation oncology. HINGE application software connects seamlessly to the local IT/medical infrastructure via interfaces and cloud services and performs data extraction and aggregation functions without human intervention. It provides tools to assess variations in radiation oncology practices and outcomes and determines gaps in radiotherapy quality delivered by each provider.

Safe zone for minimally invasive calcaneal osteotomy: an MRI study.

Hindfoot deformities are often surgically corrected with calcaneal osteotomy. These are increasingly performed via a minimally invasive approach. Identifying a neurovascular "safe zone" for this approach is important in reducing iatrogenic injury. We aimed to identify a safe zone for minimally invasive calcaneal osteotomy without neurovascular injury. Three individuals independently assessed 100 con- secutive magnetic resonance imaging ankle studies. The distance of the medial neurovascular bundle from the level of the centre of the Achilles tendon insertion was measured. The points measured were centralised in three planes (axial, sagittal and coronal). The three sets of observations were statistically analysed with confidence intervals and intraclass correlation coefficient was calculated. The mean distance measured by the three observers were 22.91 mm (range 18.2-28.5 mm); 22.81 mm (range 18.7-26.7 mm); and 23.41 mm (range 19.2- 28.4 mm); overall mean 23.0 mm. The mean inter- observer variation was 1.1 mm. 95% confidence interval for observer 1 ranges from 22.45-23.25 mm, observer 2 ranges from 22.52-23.1 mm and observer 3 ranges from 22.97-23.65 mm. Overall 95% confidence interval ranges from 22.8-23.2 mm. Intraclass correlation coefficient for inter-observer reliability is 0.7, indicating strong agreement between the observers. This radiological study suggests an anatomical "safe zone" for minimally invasive medial calcaneal osteotomy is at least 18 mm (mean: 23 mm) from the level of insertion of the Achilles tendon. Individual variation between patients must be taken in to consideration during preoperative planning.

Complex regional pain syndrome: an evolving perspective.

BACKGROUND: Complex regional pain syndrome (CRPS) is a heterogenous and poorly understood condition that can be provoked by quite minor injuries. The symptoms and signs of CRPS persist, long after the patient has recovered from the inciting event. In some cases, there is a clear association with a peripheral nerve injury. The degree of disability produced by CRPS is often out of proportion to the scale of the original insult and the condition is associated with protracted recovery times and frequent litigation. METHODS: We have performed a PubMed literature search, referenced landmark papers in the field and included a national expert in peripheral nerve injury and repair in our team of authors. RESULTS AND CONCLUSIONS: The diagnostic criteria for CRPS have changed repeatedly over the last two centuries and much of the historical literature is difficult to compare with more recent research. In this review article, we consider how our understanding of the condition has evolved and discuss its pathogenesis, its apparent heterogenicity and the various investigations and treatments available to the clinician.

Applied machine learning for predicting the lanthanide-ligand binding affinities.

Binding affinities of metal-ligand complexes are central to a multitude of applications like drug design, chelation therapy, designing reagents for solvent extraction etc. While state-of-the-art molecular modelling approaches are usually employed to gather structural and chemical insights about the metal complexation with ligands, their computational cost and the limited ability to predict metal-ligand stability constants with reasonable accuracy, renders them impractical to screen large chemical spaces. In this context, leveraging vast amounts of experimental data to learn the metal-binding affinities of ligands becomes a promising alternative. Here, we develop a machine learning framework for predicting binding affinities (logK1) of lanthanide cations with several structurally diverse molecular ligands. Six supervised machine learning algorithms-Random Forest (RF), k-Nearest Neighbours (KNN), Support Vector Machines (SVM), Kernel Ridge Regression (KRR), Multi Layered Perceptrons (MLP) and Adaptive Boosting (AdaBoost)-were trained on a dataset comprising thousands of experimental values of logK1 and validated in an external 10-folds cross-validation procedure. This was followed by a thorough feature engineering and feature importance analysis to identify the molecular, metallic and solvent features most relevant to binding affinity prediction, along with an evaluation of performance metrics against the dimensionality of feature space. Having demonstrated the excellent predictive ability of our framework, we utilized the best performing AdaBoost model to predict the logK1 values of lanthanide cations with nearly 71 million compounds present in the PubChem database. Our methodology opens up an opportunity for significantly accelerating screening and design of ligands for various targeted applications, from vast chemical spaces.

Centralizing the Cemented Exeter Femoral Stem Using the Direct Lateral Approach: Surgical Tips and Radiological Evaluation.

Varus malalignment in total hip arthroplasty has been associated with poor long-term outcomes and complications including abnormal load distribution, endosteal osteolysis, frank loosening, and periprosthetic fractures. Postoperative radiographic assessment was performed on 224 patients from our case series who underwent cemented Exeter total hip arthroplasty using the direct lateral approach alone. No patient had a true varus-aligned stem (ie, ≤-5° on the coronal assessment). We describe our surgical technique, with 4 easily reproducible technical tips to achieve positional consistency of the femoral stem: commencing stem insertion from the piriform fossa entry point, using a femoral stem distal centralizer, aiming the tip of the component to the center of the patella, and placing the thumb between the calcar and inferior neck of the femoral component to prevent the stem from tipping into varus.

Clinico-radiological outcomes following anatomical anterior cruciate ligament reconstruction using the TransLateral, all-inside technique.

We present early clinical outcomes of patients following anatomical anterior cruciate ligament reconstruction using a TransLateral, single bundle, all-inside technique with a one-year follow-up and radiological evaluation of socket position. Eligible Patients who underwent a primary ACL reconstruction, using the TransLateral, all-inside technique alone, between Jan 2013 and Feb 2016 were included in this study. Of this group, all patients underwent isolated semitendinosus graft harvest. The Lysholm knee scores were measured preoperatively and at one-year follow-up in 40 patients who underwent ACL reconstruction. Postoperatively, antero-posterior and lateral radiographs were obtained to evaluate the position of the femoral socket (using the Bernard and Hertel Grid) and tibial socket (using the Amis-Jakob line). There were 36 males and 4 females with a mean age of 27.1 years (range 16-49). There was a single non-surgical related mortality prior to the one year follow up. We report no postoperative infections or graft failure at one year. The mean preoperative Lysholm score was 68.7 (Range: 29-95). The mean Lysholm score increased to 92.5% (Range: 59-100, p < 0.05). Evaluation of femoral sockets revealed accurate positioning on the Bernard and Hertel Grid with a mean ACL center of 27% along Blumensaat's line and 34% of the height of the intercondylar notch. The mean tibial socket position was 41.8% (Range: 32%-47%) along the Amis-Jakob Line. Our single surgeon case series utilizing the all-inside, TransLateral ACLR technique highlights good early outcomes with no postoperative complications or graft failure at one year.

Phantom radiculopathy: a rare postoperative phenomenon.

Limb amputations are carried out for a number of reasons, which include trauma, vascular disorders, infection, oncology and congenital abnormalities. These patients can develop multiple complications postoperatively with phantom limb pain being a well-recognised issue. That being said, phantom radiculopathy is far less encountered and can therefore be easily overlooked. There are limited cases described in literature and as a result pathophysiology is poorly understood. In this report, we present a patient who had developed phantom radiculopathy decades after his left above knee amputation surgery, which was performed after a road traffic accident. However, we were successfully able to treat the patient with foraminal epidural corticosteroid injection.

Hydration structure and water exchange kinetics at xenotime-water interfaces: implications for rare earth minerals separation.

Hydration of surface ions gives rise to structural heterogeneity and variable exchange kinetics of water at complex mineral-water interfaces. Here, we employ ab initio molecular dynamics (AIMD) simulations and water adsorption calorimetry to examine the aqueous interfaces of xenotime, a phosphate mineral that contains predominantly Y3+ and heavy rare earth elements. Consistent with natural crystal morphology, xenotime is predicted to have a tetragonal prismatic shape, dominated by the {100} surface. Hydration of this surface induces multilayer interfacial water structures with distinct OH orientations, which agrees with recent crystal truncation rod measurements. The exchange kinetics between two adjacent water layers exhibits a wide range of underlying timescales (5-180 picoseconds), dictated by ion-water electrostatics. Adsorption of a bidentate hydroxamate ligand reveals that {100} xenotime surface can only accommodate monodentate coordination with water exchange kinetics strongly depending on specific ligand orientation, prompting us to reconsider traditional strategies for selective separation of rare-earth minerals.

Interfacial structure in the liquid-liquid extraction of rare earth elements by phosphoric acid ligands: a molecular dynamics study.

Solvent extraction (SX), wherein two immiscible liquids, one containing the extractant molecules and the other containing the solute to be extracted are brought in contact to effect the phase transfer of the solute, underpins metal extraction and recovery processes. The interfacial region is of utmost importance in the SX process, since besides thermodynamics, the physical and chemical heterogeneity at the interface governs the kinetics of the process. Yet, a fundamental understanding of this heterogeneity and its implications for the extraction mechanism are currently lacking. We use molecular dynamics (MD) simulations to study the liquid-liquid interface under conditions relevant to the SX of Rare Earth Elements (REEs) by a phosphoric acid ligand. Simulations revealed that the extractant molecules and varying amounts of acid and metal ions partitioned to the interface. The presence of these species had a significant effect on the interfacial thickness, hydrogen bond life times and orientations of the water molecules at the interface. Deprotonation of the ligands was essential for the adsorption of the metal ions at the interface, with these ions forming a number of different complexes at the interface involving one to three extractant molecules and four to eight water molecules. Although the interface itself was rough, no obvious 'finger-like' water protrusions penetrating the organic phase were seen in our simulations. While the results of our work help us gain fundamental insights into the sequence of events leading to the formation of a variety of interfacial complexes, they also emphasize the need to carry out a more detailed atomic level study to understand the full mechanism of extraction of REEs from the aqueous to organic phases by phosphoric acid ligands.

Bulk and surface DFT investigations of inorganic halide perovskites screened using machine learning and materials property databases.

In the recent past, there has been proliferation in high-throughput density functional theory and data-driven explorations of materials motivated by a need to reduce physical testing and costly computations for materials discovery. This has, in conjunction with the development of open-access materials property databases, encouraged accelerated and more streamlined discovery and screening of technologically relevant materials. In this work, we report our results on the screening and DFT studies of one such class of materials, i.e. ABX3 inorganic halide perovskites (A, B and X representing the monovalent, divalent and halide ions respectively) using a coupled machine-learning (ML) and density functional theory (DFT) approach. Utilizing the support vector machine algorithm, we predict the formability of 454 inorganic halide compounds in the perovskite phase. Compounds with a formation probability P≥ 0.8 are further checked for thermodynamic stability in at least one of these three open materials databases - Materials Project (MP), Automatic FLOW for Materials Discovery (AFLOW) and Open Quantum Materials Database (OQMD). The shortlisted candidate perovskites are then considered for DFT computations. Taking input geometries from MP's structure predictor, the optimized lattice parameters and computed band gaps (BG) for all screened compounds are compared with predictions across all databases. Subsequently, detailed studies on low index surfaces are presented for two halide perovksites - RbSnCl3 and RbSnBr3- having band-gaps in the favourable range for photovoltaics (PV). Different possible (100), (110) and (111) surface terminations are investigated for each of these compositions and the atomic relaxations, surface energies and electronic band structures are reported for each termination. To the best of our knowledge, no surface studies have been reported in the literature for any of the halide perovskites present in our database. These studies, therefore, are an important step towards gaining a fundamental understanding of the interfacial properties of perovskites, which can help facilitate further breakthroughs in the PV technology.

Bivalent rLP2086 (Trumenba®): Development of a well-characterized vaccine through commercialization.

The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation. Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B in individuals 10-25years of age in the United States. This paper discusses the development of the manufacturing process of the two antigens for the purpose of making it amenable to any manufacturing facility. For the journey to commercialization, the operating model used to manage this highly accelerated program led to a framework that ensured "right the first time" execution, robust process characterization, and proactive process monitoring. This framework enabled quick problem identification and proactive resolutions, resulting in a robust control strategy for the commercial process.