Synthetic electronic health records generated with variational graph autoencoders.

Data-driven medical care delivery must always respect patient privacy-a requirement that is not easily met. This issue has impeded improvements to healthcare software and has delayed the long-predicted prevalence of artificial intelligence in healthcare. Until now, it has been very difficult to share data between healthcare organizations, resulting in poor statistical models due to unrepresentative patient cohorts. Synthetic data, i.e., artificial but realistic electronic health records, could overcome the drought that is troubling the healthcare sector. Deep neural network architectures, in particular, have shown an incredible ability to learn from complex data sets and generate large amounts of unseen data points with the same statistical properties as the training data. Here, we present a generative neural network model that can create synthetic health records with realistic timelines. These clinical trajectories are generated on a per-patient basis and are represented as linear-sequence graphs of clinical events over time. We use a variational graph autoencoder (VGAE) to generate synthetic samples from real-world electronic health records. Our approach generates health records not seen in the training data. We show that these artificial patient trajectories are realistic and preserve patient privacy and can therefore support the safe sharing of data across organizations.

Delayed dorsal scapular artery hematoma following blunt thoracic trauma: a case report and review of the literature.

BACKGROUND: The present case contributes to the limited literature on delayed chest wall hematomas following blunt trauma. The literature review provides a summary of similar previously reported cases. CASE PRESENTATION: We report the case of a 59-year-old Caucasian male who presented to the emergency department with a rapidly expanding chest wall hematoma. Six weeks earlier, he had sustained multiple rib fractures and a pneumothorax after falling 4 m from a ladder. Computed tomography angiography was used to identify two sources of active bleeding on the left dorsal scapular artery. The patient underwent surgery with evacuation of the hematoma and ligation of the artery. The patient was hospitalized for 3 days and recovered with no sequelae. CONCLUSIONS: A literature review revealed eight previously reported cases of chest wall hematomas exterior to the endothoracic fascia following blunt trauma. Most cases were initially diagnosed by computed tomography of the chest and finally by angiogram. Management options range from surgical drainage to angiographic embolization. This case is unusual regarding the delay in the development of the hematoma and illustrates the importance of considering this diagnosis even weeks after relevant trauma.

First principles characterisation of bio-nano interface.

Nanomaterials possess a wide range of potential applications due to their novel properties and exceptionally high activity as a result of their large surface to volume ratios compared to bulk matter. The active surface may present both advantage and risk when the nanomaterials interact with living organisms. As the overall biological impact of nanomaterials is triggered and mediated by interactions at the bio-nano interface, an ability to predict those from the atomistic descriptors, especially before the material is produced, can present enormous advantage for the development of nanotechnology. Fast screening of nanomaterials and their variations for specific biological effects can be enabled using computational materials modelling. The challenge lies in the range of scales that needs to be crossed from the material-specific atomistic representation to the relevant length scales covering typical biomolecules (proteins and lipids). In this work, we present a systematic multiscale approach that allows one to evaluate crucial interactions at the bionano interface from the first principles without any prior information about the material and thus establish links between the details of the nanomaterials structure to protein-nanoparticle interactions. As an example, an advanced computational characterization of titanium dioxide nanoparticles (6 different surfaces of rutile and anatase polymorphs) has been performed. We computed characteristics of the titanium dioxide interface with water using density functional theory for electronic density, used these parameters to derive an atomistic force field, and calculated adsorption energies for essential biomolecules on the surface of titania nanoparticles via direct atomistic simulations and coarse-grained molecular dynamics. Hydration energies, as well as adsorption energies for a set of 40 blood proteins are reported.

Atomistic Perspective on Biomolecular Adsorption on Functionalized Carbon Nanomaterials under Ambient Conditions.

The use of carbon-based nanomaterials is tremendously increasing in various areas of technological, bioengineering, and biomedical applications. The functionality of carbon-based nanomaterials can be further broadened via chemical functionalization of carbon nanomaterial surfaces. On the other hand, concern is rising on possible adverse effects when nanomaterials are taken up by biological organisms. In order to contribute into understanding of interactions of carbon-based nanomaterials with biological matter, we have investigated adsorption of small biomolecules on nanomaterials using enhanced sampling molecular dynamics. The biomolecules included amino acid side chain analogues, fragments of lipids, and sugar monomers. The adsorption behavior on unstructured amorphous carbon, pristine graphene and its derivatives (such as few-layer graphene, graphene oxide, and reduced graphene oxide) as well as pristine carbon nanotubes, and those functionalized with OH-, COOH-, COO-, NH2-, and NH3+ groups was investigated with respect to surface concentration. An adsorption profile, that is, the free energy as a function of distance from the nanomaterial surfaces, was determined for each molecule and surface using the Metadynamics approach. The results were analyzed in terms of chemical specificity, surface charge, and surface concentration. It was shown that although morphology of the nanomaterial has a limited effect on the adsorption properties, functionalization of the surface by various molecular groups can drastically change the adsorption behavior that can be used in the design of nanosurfaces with highly selective adsorption properties and safe for human health and environment.

Acute Tentorial Subdural Hematoma Caused by Rupture of the Posterior Cerebral Artery after Minor Trauma-A Case Report.

Acute subdural hematoma (aSDH) is a common pathology encountered after head trauma. Only a minority of aSDHs have an arterial source. In this article, we report a case of aSDH originating from a traumatic pseudoaneurysm of the distal segment of posterior cerebral artery (PCA), diagnosed several days after the initial minor trauma and successfully treated with endovascular coiling. This case emphasizes the importance of searching for vascular pathology when the localization, severity or relapsing course of the intracranial hemorrhage does not fully correspond to the severity of initial trauma and when the bleeding has a delayed onset. Characteristics, diagnostics and treatment possibilities of traumatic cerebral aneurysms, an important cause of arterial aSDH, are described in the article.

Curvature sensing by cardiolipin in simulated buckled membranes.

Cardiolipin is a non-bilayer phospholipid with a unique dimeric structure. It localizes to negative curvature regions in bacteria and is believed to stabilize respiratory chain complexes in the highly curved mitochondrial membrane. Cardiolipin's localization mechanism remains unresolved, because important aspects such as the structural basis and strength for lipid curvature preferences are difficult to determine, partly due to the lack of efficient simulation methods. Here, we report a computational approach to study curvature preferences of cardiolipin by simulated membrane buckling and quantitative modeling. We combine coarse-grained molecular dynamics with simulated buckling to determine the curvature preferences in three-component bilayer membranes with varying concentrations of cardiolipin, and extract curvature-dependent concentrations and lipid acyl chain order parameter profiles. Cardiolipin shows a strong preference for negative curvatures, with a highly asymmetric chain order parameter profile. The concentration profiles are consistent with an elastic model for lipid curvature sensing that relates lipid segregation to local curvature via the material constants of the bilayers. These computations constitute new steps to unravel the molecular mechanism by which cardiolipin senses curvature in lipid membranes, and the method can be generalized to other lipids and membrane components as well.

Sarcopenia predicts 90-day mortality in elderly patients undergoing emergency abdominal surgery.

PURPOSE: Image-based measurement of sarcopenia is an established predictor of a decreased outcome for a large variety of surgical procedures. Sarcopenia in elderly patients undergoing emergency abdominal surgery has not been well studied. This study aims to investigate the association between the total psoas area (TPA) and postoperative mortality after 90 days in a group of elderly emergency laparotomy patients. METHODS: We retrospectively reviewed the emergency CT-scans of 150 elderly patients from a consecutive cohort undergoing emergency abdominal surgery at our surgical center. TPA was measured manually at the level of L3 and indexed to patient height. Sarcopenia was defined as having a TPA index below the first quartile for gender in the cohort. Other collected variables were age, vital status/date of death, ASA-score, surgical procedure, and WHO performance score. RESULTS: Overall 90-day mortality was 42.7%. Sarcopenic patients had a higher 90-day mortality (60.5%) than non-sarcopenic patients (36.6%), corresponding to an odds ratio of 2.66 (95% confidence interval 1.2-5.7, p = 0.01). Sarcopenic patients had an increased mortality compared with non-sarcopenic patients (p = 0.0009, Log-rank test), with a clear separation of the two groups within 30 days postoperatively. In a multivariate logistic regression model, with age, ASA-score, and WHO performance score as covariates, sarcopenia was independently associated with 90-day mortality. CONCLUSION: Manual measurement of TPA on an abdominal CT-scan is a relevant risk factor for postoperative mortality in elderly patients undergoing high-risk emergency abdominal surgery. Incorporation of sarcopenia in postoperative risk-prediction models in emergency abdominal surgery should be considered.

Insights into Functionalization of Metal-Organic Frameworks Using In Situ NMR Spectroscopy.

Postsynthetic reactions of metal-organic frameworks (MOFs) are versatile tools for producing functional materials, but the methods of evaluating these reactions are cumbersome and destructive. Here we demonstrate and validate the use of in situ NMR spectroscopy of species in the liquid state to examine solvent-assisted ligand exchange (SALE) and postsynthetic modification (PSM) reactions of metal-organic frameworks. This technique allows functionalization to be monitored over time without decomposing the product for analysis, which simplifies reaction screening. In the case of SALE, both the added ligand and the ligand leaving the framework can be observed. We demonstrate this in situ method by examining SALE and PSM reactions of the robust zirconium MOF UiO-67 as well as SALE with the aluminum MOF DUT-5. In situ NMR spectroscopy provided insights into the reactions studied, and we expect that future studies using this method will permit the examination of a variety of MOF-solute reactions.

Computing Curvature Sensitivity of Biomolecules in Membranes by Simulated Buckling.

Membrane curvature sensing, where the binding free energies of membrane-associated molecules depend on the local membrane curvature, is a key factor to modulate and maintain the shape and organization of cell membranes. However, the microscopic mechanisms are not well understood, partly due to absence of efficient simulation methods. Here, we describe a method to compute the curvature dependence of the binding free energy of a membrane-associated probe molecule that interacts with a buckled membrane, which has been created by lateral compression of a flat bilayer patch. This buckling approach samples a wide range of curvatures in a single simulation, and anisotropic effects can be extracted from the orientation statistics. We develop an efficient and robust algorithm to extract the motion of the probe along the buckled membrane surface, and evaluate its numerical properties by extensive sampling of three coarse-grained model systems: local lipid density in a curved environment for single-component bilayers, curvature preferences of individual lipids in two-component membranes, and curvature sensing by a homotrimeric transmembrane protein. The method can be used to complement experimental data from curvature partition assays and provides additional insight into mesoscopic theories and molecular mechanisms for curvature sensing.

Traumatic separation of osseous segments in a double-layered patella.

INTRODUCTION: Double-layered patella is a rare intra-articular disorder associated with multiple epiphyseal dysplasia. PRESENTATION OF CASE: We present a case of a 40-year old man with acute pain in his left knee after a tackle during soccer play. DISCUSSION: Clinical examination and radiographs confirmed the diagnosis of a bilateral double-layered patella with traumatic separation of the osseous segments on the afflicted left side. Surgical management comprised of open arthrotomy and debridement of the bony interface. Stabilization was performed with tension cerclage, supported by a lag screw with excellent outcome at 12 months follow-up. CONCLUSION: It is possible that micromovement in a double-layered patella can dispose to a traumatic coronal segment displacement. Osseous fusion of traumatic patellar segments can be achieved.

Diffusion and reaction pathways of water near fully hydrated TiO2 surfaces from ab initio molecular dynamics.

Ab initio molecular dynamics simulations are reported for water-embedded TiO2 surfaces to determine the diffusive and reactive behavior at full hydration. A three-domain model is developed for six surfaces [rutile (110), (100), and (001), and anatase (101), (100), and (001)] which describes waters as "hard" (irreversibly bound to the surface), "soft" (with reduced mobility but orientation freedom near the surface), or "bulk." The model explains previous experimental data and provides a detailed picture of water diffusion near TiO2 surfaces. Water reactivity is analyzed with a graph-theoretic approach that reveals a number of reaction pathways on TiO2 which occur at full hydration, in addition to direct water splitting. Hydronium (H3O+) is identified to be a key intermediate state, which facilitates water dissociation by proton hopping between intact and dissociated waters near the surfaces. These discoveries significantly improve the understanding of nanoscale water dynamics and reactivity at TiO2 interfaces under ambient conditions.

Multiscale Modelling of Bionano Interface.

We present a framework for coarse-grained modelling of the interface between foreign nanoparticles (NP) and biological fluids and membranes. Our model includes united-atom presentations of membrane lipids and globular proteins in implicit solvent, which are based on all-atom structures of the corresponding molecules and parameterised using experimental data or atomistic simulation results. The NPs are modelled by homogeneous spheres that interact with the beads of biomolecules via a central force that depends on the NP size. The proposed methodology is used to predict the adsorption energies for human blood plasma proteins on NPs of different sizes as well as the preferred orientation of the molecules upon adsorption. Our approach allows one to rank the proteins by their binding affinity to the NP, which can be used for predicting the composition of the NP-protein corona for the corresponding material. We also show how the model can be used for studying NP interaction with a lipid bilayer membrane and thus can provide a mechanistic insight for modelling NP toxicity.

Reactive wetting properties of TiO2 nanoparticles predicted by ab initio molecular dynamics simulations.

Small-sized wet TiO2 nanoparticles have been investigated by ab initio molecular dynamics simulations. Chemical and physical adsorption of water on the TiO2-water interface was studied as a function of water content, ranging from dry nanoparticles to wet nanoparticles with monolayer coverage of water. The surface reactivity was shown to be a concave function of water content and driven by surface defects. The local coordination number at the defect was identified as the key factor to decide whether water adsorption proceeds through dissociation or physisorption on the surface. A consistent picture of TiO2 nanoparticle wetting at the microscopic level emerges, which corroborates existing experimental data and gives further insight into the molecular mechanisms behind nanoparticle wetting. These calculations will facilitate the engineering of metal oxide nanoparticles with a controlled catalytic water activity.

[Cerebral fat emboli after elective total hip replacement]. / Cerebrale fedtembolierefter elektiv total hoftealloplastik.

Fat embolism is a well known complication to fractures of long bones, but is less often seen after surgery. The symptoms vary from non- to total pulmonary and circulatory collapse and also include cerebral affection. Cerebral fat embolism is less common, and with varying presentation. This case report describes a case of fatal cerebral fat embolism after total hip replacement in a 75-year-old male. Diagnostics can be difficult but diffusion-weighted MRI can detect infarctions at an early stage. Treatment is symptomatic, and there is often total spontaneous remission of symptoms.

No difference in incidence of port-site hernia and chronic pain after single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy: a nationwide prospective, matched cohort study.

BACKGROUND: Conventional laparoscopic cholecystectomy (CLC) is regarded as the gold standard for cholecystectomy. However, single-incision laparoscopic cholecystectomy (SLC) has been suggested to replace CLC. This study aimed at comparing long-term incidences of port-site hernia and chronic pain after SLC versus CLC. METHODS: We conducted a matched cohort study based on prospective data (Jan 1, 2009-June 1, 2011) from the Danish Cholecystectomy Database with perioperative information and clinical follow-up. Consecutive patients undergoing elective SLC during the study period were included and matched 1:2 with patients subjected to CLC using pre-defined criteria. Follow-up data were obtained from the Danish National Patient Registry, mailed patient questionnaires, and clinical examination. A port-site hernia was defined as a repair for a port-site hernia or clinical hernia located at one or more port sites. RESULTS: In total, 699 patients were eligible and 147 patients were excluded from the analysis due to pre-defined criteria. The rate of returned questionnaires was 83%. Thus, 552 (SLC, n = 185; CLC, n = 367) patients were analyzed. The median observation time was 48 months (range 1-65) after SLC and 48 months (1-64) after CLC (P = 0.940). The total cumulated port-site hernia rate was 4 % and 6 % for SLC and CLC, respectively (P = 0.560). Incidences of moderate/severe chronic pain were 4 % and 5 % after SLC and CLC, respectively (P = 0.661). CONCLUSIONS: We found no difference in long-term incidence of port-site hernia or chronic pain after SLC versus CLC.

Dynamic implicit-solvent coarse-grained models of lipid bilayer membranes: fluctuating hydrodynamics thermostat.

We introduce a thermostat based on fluctuating hydrodynamics for dynamic simulations of implicit-solvent coarse-grained models of lipid bilayer membranes. We show our fluctuating hydrodynamics approach captures interesting correlations in the dynamics of lipid bilayer membranes that are missing in simulations performed using standard Langevin dynamics. Our momentum conserving thermostat accounts for solvent-mediated momentum transfer by coupling coarse-grained degrees of freedom to stochastic continuum fields that account for both the solvent hydrodynamics and thermal fluctuations. We present both a general framework and specific methods to couple the particle and continuum degrees of freedom in a manner consistent with statistical mechanics and amenable to efficient computational simulation. For self-assembled vesicles, we study the diffusivity of lipids and their spatial correlations. We find the hydrodynamic coupling yields within the bilayer interesting correlations between diffusing lipids that manifest as a vortex-like structure similar to those observed in explicit-solvent simulations. We expect the introduced fluctuating hydrodynamics methods to provide a way to extend implicit-solvent models for use in a wide variety of dynamic studies.

Fluctuating hydrodynamics simulations of coarse-grained lipid membranes under steady-state conditions and in shear flow.

The stochastic Eulerian-Lagrangian method (SELM) is used to simulate coarse-grained lipid membrane models under steady-state conditions and in shear flow. SELM is an immersed boundary method which combines the efficiency of particle-based simulations with the realistic solvent dynamics provided by fluctuating hydrodynamics. Membrane simulations in SELM are shown to give structural properties in accordance with equilibrium statistical mechanics and dynamic properties in agreement with previous simulations of highly detailed membrane models in explicit solvent. Simulations of sheared membranes are used to calculate surface shear viscosities and inter-monolayer friction coefficients. The membrane models are shown to be shear thinning under a wide range of applied shear rates.

[Intra-abdominal undifferentiated high-grade pleomorphic sarcoma as the cause of mechanical bowel obstruction]. / Intraabdominalt udifferentieret high-grade pleomorft sarkom som årsag til mekanisk tyndtarmsileus.

Primary intra-abdominal undifferentiated high-grade pleomorphic sarcoma is rare with only 40 cases described worldwide. We describe a case of a patient who presented with mechanical bowel obstruction with abdominal undifferentiated high-grade pleomorphic sarcoma. Five-year survival rates have been reported as low as 40-55%, especially due to late diagnosis. Rare diagnoses as in our patient emphasize the need for close collaboration between pathologists, radiologists and surgeons.

A minority of patients discharged within 24 hours after laparoscopic colon resection.

INTRODUCTION: Fast-track laparoscopic colon surgery has gained wide acceptance worldwide. Post-operative hospital stays of 2-5 days have typically been reported. However, in our department some of the patients have been discharged within 24 h after surgery. The aim of this study was to describe differences in demographic and perioperative data between those patients discharged within 24 h and those discharged on days 2-4 post-operatively. MATERIAL AND METHODS: Data were collected retrospectively from August 2008 to May 2012. A total of 24 patients undergoing elective right-sided hemicolectomy or sigmoidectomy for colon cancer were discharged within 24 h. These 24 patients were compared with 209 patients undergoing the same procedures, but discharged on the second to the fourth post-operative day. All patients were operated laparoscopically according to our fast-track regimen. Demographic data and short-term outcomes were compared between the two groups. RESULTS: We found that the median age (64 years versus 70 years) (p = 0.018) as well as the median operating time (120 min. versus 155 min.) (p = 0.002) were significantly lower for the 24-h stay group. No other significant differences were found between the two groups. CONCLUSION: This study showed that discharge within the first 24 h after elective laparoscopic fast-track colon surgery was significantly associated with lower age and shorter duration of surgery. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Determining biomembrane bending rigidities from simulations of modest size.

Thermal fluctuations of lipid orientation are analyzed to infer the bending rigidity of lipid bilayers directly from molecular simulations. Compared to the traditional analysis of thermal membrane undulations, the proposed method is reliable down to shorter wavelengths and allows for determination of the bending rigidity using smaller simulation boxes. The requisite theoretical arguments behind this analysis are presented and verified by simulations spanning a diverse range of lipid models from the literature.