A viscoactive constitutive modeling framework with variational updates for the myocardium.

We present a constitutive modeling framework for contractile cardiac mechanics by formulating a single variational principle from which incremental stress-strain relations and kinetic rate equations for active contraction and relaxation can all be derived. The variational framework seamlessly incorporates the hyperelastic behavior of the relaxed and contracted tissue along with the rate - and length - dependent generation of contractile force. We describe a three-element, Hill-type model that unifies the active tension and active deformation approaches. As in the latter approach, we multiplicatively decompose the total deformation gradient into active and elastic parts, with the active deformation parametrizing the contractile Hill element. We adopt as internal variables the fiber, cross-fiber, and sheet normal stretch ratios. The kinetics of these internal variables are modeled via definition of a kinetic potential function derived from experimental force-velocity relations. Additionally, we account for dissipation during tissue deformation by adding a Newtonian viscous potential. To model the force activation, the kinetic equations are coupled with the calcium transient obtained from a cardiomyocyte electrophysiology model. We first analyze our model at the material point level using stress and strain versus time curves for different viscosity values. Subsequently, we couple our constitutive framework with the finite element method (FEM) and study the deformation of three-dimensional tissue slabs with varying cardiac myocyte orientation. Finally, we simulate the contraction and relaxation of an ellipsoidal left ventricular model and record common kinematic measures, such as ejection fraction, and myocardial tissue volume changes.

Lumbar neuraxial anatomical changes throughout pregnancy: a longitudinal study using serial ultrasound scans.

This observational study was designed to investigate the anatomical changes of the lumbar spine over the course of pregnancy using serial ultrasound scans. We performed paramedian scans on 58 women at the L2-3, L3-4 and L4-5 levels; these were done at four periods of 11+0-13+6, 19+0-23+0, 28+0-32+0 and 38+0-40+0 weeks gestation. At each intervertebral level, the length of the interlaminar space, length of the visible intervertebral posterior dura and depth of the posterior dura mater from the skin were measured. The length of the interlaminar space and length of the visible intervertebral posterior dura mater were longer, and the depth of the posterior dura mater was shallower, with ascending spinal interspace. The depth of the posterior dura mater increased during pregnancy, although it plateaued between the third and fourth measurement periods. The other spinal measurements were not affected by gestation. These findings indicate that the L2-3 level is the most appropriate puncture site for epidural anaesthesia in pregnant women. Our results ought to be embraced as a departure point towards developing neuraxial insertion techniques guided or aided by ultrasound.

Statistical Physics of Viral Capsids with Broken Symmetry.

We present a model to understand quantitatively the role of symmetry breaking in assembly of macromolecular aggregates in general, and the protein shells of viruses in particular. A simple dodecahedral lattice model with a quadrupolar order parameter allows us to demonstrate how symmetry breaking may reduce the probability of assembly errors and, consequently, enhance assembly efficiency. We show that the ground state is characterized by large-scale cooperative zero-energy modes. In analogy with other models, this suggests a general physical principle: the tendency of biological molecules to generate symmetric structures competes with the tendency to break symmetry in order to achieve specific functional goals.

A retrospective analysis of 509 consecutive interscalene catheter insertions for ambulatory surgery.

Effective pain therapy after shoulder surgery is the main prerequisite for safe management in an ambulatory setting. We evaluated adverse events and hospital re-admission using a database of 509 interscalene catheters inserted during ambulatory shoulder surgery. Adverse events were recorded for 34 (6.7%) patients (9 (1.8%) catheter dislocations diagnosed in the recovery room, 9 (1.8%) catheter dislocations at home with pain, 2 (0.4%) pain without catheter dislocation, 1 (0.2%) 'secondary' pneumothorax without intervention and 13 (2.6%) other). Twelve (2.4%) patients were re-admitted to hospital (8 (1.6%) for pain, 2 (0.4%) for dyspnoea and 2 (0.4%) for nausea and vomiting), 9 of whom had rotator cuff repair. A well-organised infrastructure, optimally trained medical professionals and appropriate patient selection are the main prerequisites for the safe, effective implementation of ambulatory interscalene catheters in routine clinical practice.

Elasticity theory of macromolecular aggregates.

We present a version of continuum elasticity theory applicable to aggregates of functional biomolecules at length scales comparable to that of the component molecules. Unlike classical elasticity theory, the stress and strain fields have mathematical discontinuities along the interfaces of the macromolecules, due to conformational incompatibility and large scale conformational transitions. The method is applied to the P-II to EI shape transition of the protein shell of the virus HK97. We show that protein residual stresses generated by incompatibility drive a "reverse buckling" transition from an icosahedral to a dodecahedral shape via a "critical" spherical shape, which can be identified as the P-II state.

Unlocking internal prestress from protein nanoshells.

The capsids of icosahedral viruses are closed shells assembled from a hexagonal lattice of proteins with fivefold angular defects located at the icosahedral vertices. Elasticity theory predicts that these disclinations are subject to an internal compressive prestress, which provides an explanation for the link between size and shape of capsids. Using a combination of experiment and elasticity theory we investigate the question of whether macromolecular assemblies are subject to residual prestress, due to basic geometric incompatibility of the subunits. Here we report the first direct experimental test of the theory: by controlled removal of protein pentamers from the icosahedral vertices, we measure the mechanical response of so-called "whiffle ball" capsids of herpes simplex virus, and demonstrate the signature of internal prestress locked into wild-type capsids during assembly.

Morphological phase diagram for lipid membrane domains with entropic tension.

Circular domains in phase-separated lipid vesicles with symmetric leaflet composition commonly exhibit three stable morphologies: flat, dimpled, and budded. However, stable dimples (i.e., partially budded domains) present a puzzle since simple elastic theories of domain shape predict that only flat and spherical budded domains are mechanically stable in the absence of spontaneous curvature. We argue that this inconsistency arises from the failure of the constant surface tension ensemble to properly account for the effect of entropic bending fluctuations. Formulating membrane elasticity within an entropic tension ensemble, wherein tension represents the free energy cost of extracting membrane area from thermal bending of the membrane, we calculate a morphological phase diagram that contains regions of mechanical stability for each of the flat, dimpled, and budded domain morphologies.

Squeezing protein shells: how continuum elastic models, molecular dynamics simulations, and experiments coalesce at the nanoscale.

The current rapid growth in the use of nanosized particles is fueled in part by our increased understanding of their physical properties and ability to manipulate them, which is essential for achieving optimal functionality. Here we report detailed quantitative measurements of the mechanical response of nanosized protein shells (viral capsids) to large-scale physical deformations and compare them with theoretical descriptions from continuum elastic modeling and molecular dynamics (MD). Specifically, we used nanoindentation by atomic force microscopy to investigate the complex elastic behavior of Hepatitis B virus capsids. These capsids are hollow, approximately 30 nm in diameter, and conform to icosahedral (5-3-2) symmetry. First we show that their indentation behavior, which is symmetry-axis-dependent, cannot be reproduced by a simple model based on Föppl-von Kármán thin-shell elasticity with the fivefold vertices acting as prestressed disclinations. However, we can properly describe the measured nonlinear elastic and orientation-dependent force response with a three-dimensional, topographically detailed, finite-element model. Next, we show that coarse-grained MD simulations also yield good agreement with our nanoindentation measurements, even without any fitting of force-field parameters in the MD model. This study demonstrates that the material properties of viral nanoparticles can be correctly described by both modeling approaches. At the same time, we show that even for large deformations, it suffices to approximate the mechanical behavior of nanosized viral shells with a continuum approach, and ignore specific molecular interactions. This experimental validation of continuum elastic theory provides an example of a situation in which rules of macroscopic physics can apply to nanoscale molecular assemblies.

Supraclavicular ultrasound-guided catheterization of the brachiocephalic vein in infants and children: A retrospective analysis.

OBJECTIVE/BACKGROUND: Ultrasound (US) facilitates central venous catheter (CVC) placement in children. A new supraclavicular approach using the brachiocephalic vein (BCV) for US-guided CVC placement in very small children has been recently described. In 2012, we changed our departmental standard and used the left BCV as preferred puncture site during CVC placement. In our retrospective analysis, we compared US-guided cannulation of the BCV with other puncture sites (control). DESIGN/MATERIALS AND METHODS: We performed a retrospective analysis of all CVC cannulations from October 2012 to October 2013 in our department. For cannulation of the BCV, the in-plane technique was used to guide the needle into the target vein. RESULTS: We performed CVC cannulations in 106 children (age 1-day to 18 years). In 29 patients, the weight was <4.5 kg. CVC placement was successful in all patients. The left BCV could be used in 81.1% of all cases. In a Poisson regression model of punctures regressed by age, weight or group (left BCV vs. control), age, weight or the cannulation site did not influence the number of punctures. In a logistic regression model of complications (yes vs. no) regressed by the group (left brachiocephalic vs. control) an odds ratio of 0.15 was observed (95% confidence interval 0.03-0.72, P likelihood ratio test = 0.007). CONCLUSION: US-guided puncture of the left BCV is a safe method of CVC placement in children. The use of the left BCV was associated with a high success rate in our retrospective analysis.

Useful scars: Physics of the capsids of archaeal viruses.

We propose a physical model for the capsids of tailed archaeal viruses as viscoelastic membranes under tension. The fluidity is generated by thermal motion of scarlike structures that are an intrinsic feature of the ground state of large particle arrays covering surfaces with nonzero Gauss curvature. The tension is generated by a combination of the osmotic pressure of the enclosed genome and an extension force generated by filamentous structure formation that drives the formation of the tails. In continuum theory, the capsid has the shape of a surface of constant mean curvature: an unduloid. Particle arrays covering unduloids are shown to exhibit pronounced subdiffusive and diffusive single-particle transport at temperatures that are well below the melting temperature of defect-free particle arrays on a surface with zero Gauss curvature.

Preoperative cobalt60 irradiation delays the healing of rectal anastomoses in rats.

The healing of colorectal anastomoses after irradiation therapy continues to be a major concern. The authors evaluated the healing of rectal anastomoses in a rat model after a preoperative 500-cGy dose of cobalt60 irradiation. Thirty-six male Wistar rats were divided into two equal groups: control (group A), and irradiation group (group B). Group B received a single 500-cGy dose of irradiation, and a rectal resection and end-to-end anastomosis was performed in both groups on the 7th day after irradiation. Parameters of the healing process included bursting pressure and collagen content on the 5th, 7th, and 14th days after surgery. In the irradiation group, the mean bursting pressure on the 5th, 7th, and 14th days was 116, 218, and 273 mmHg, respectively. The collagen content assessed by histomorphometry was 9.0, 20.8, and 32%, respectively. In contrast, the control group had a mean bursting pressure of 175, 225 and 263 mmHg, and a collagen content of 17.8, 28.1, and 32.1%, respectively. The adverse effect of irradiation on healing was detectable only on the 5th postoperative day, as demonstrated by lower bursting pressure (P < 0.013) and collagen content (P < 0.008). However, there was no failure of anastomotic healing such as leakage or dehiscence due to irradiation. We conclude that a single preoperative 500-cGy dose of irradiation delays the healing of rectal anastomosis in rats.

Regional segmentation of ventricular models to achieve repolarization dispersion in cardiac electrophysiology modeling.

The electrocardiogram (ECG) is one of the most significant outputs of a computational model of cardiac electrophysiology because it relates the numerical results to clinical data and is a universal tool for diagnosing heart diseases. One key features of the ECG is the T-wave, which is caused by longitudinal and transmural heterogeneity of the action potential duration (APD). Thus, in order to model a correct wave of repolarization, different cell properties resulting in different APDs must be assigned across the ventricular wall and longitudinally from apex to base. To achieve this requirement, a regional parametrization of the heart is necessary. We propose a robust approach to obtain the transmural and longitudinal segmentation in a general heart geometry without relying on ad hoc procedures. Our approach is based on auxiliary harmonic lifting analyses, already used in the literature to generate myocardial fiber orientations. Specifically, the solution of a sequence of Laplace boundary value problems allows parametrically controlled segmentation of both heart ventricles. The flexibility and simplicity of the proposed method is demonstrated through several representative examples, varying the locations and extents of the epicardial, midwall, and endocardial layers. Effects of the control parameters on the T-wave morphology are illustrated via computed ECGs.

[Ambulatory visceral surgery--limits and risks from the clinical viewpoint]. / Ambulante Visceralchirurgie--Grenzen und Risiken aus klinischer Sicht.

Visceral outpatient operations are well established in Dresden. Since 1978, 13,948 cases have been operated on in general surgery. Most patients (57.8%) had local anesthesia; only 9.2% needed general anesthesia. A total of 9,175 patients (65.8%) had visceral outpatient surgery. The conditions for these operations in outpatients are: the patient's compliance, the cooperation of the family, an operating theater with complete equipment and, last but not least, a qualified surgical team. The pre- and postoperative management must be perfectly organized. Even today there are special limitation for one-day surgery. We have not yet introduced laparoscopy into our outpatient program. Oncological surgery can be performed, provided the general standards for radical tumor surgery can be realized. With careful selection of patients and the right indication, complications are rare in outpatient surgery. In only 0.7% of all cases did wound infections occur postoperatively. None of the patients died.

Can the confidence in long range atmospheric transport models be increased? The pan-european experience of ensemble.

Is atmospheric dispersion forecasting an important asset of the early-phase nuclear emergency response management? Is there a 'perfect atmospheric dispersion model'? Is there a way to make the results of dispersion models more reliable and trustworthy? While seeking to answer these questions the multi-model ensemble dispersion forecast system ENSEMBLE will be presented.

[Ozone-oxygen therapy in proctology]. / Ozon-kislorodnaia terapiia v proktologii.

The diffusion of oxygen through the colon wall could be demonstrated in animal experiment. The relevant rise in PaO2 can be evidenced both in blood vessels and in the liver, whereby a significantly high increase of 250% above the normal value was recorded in the region of the intestinal wall. The venous blood values were at 230%, those in the portal vein at 134%, and in the liver parenchyma at 127%. When ozone is applied, these values are even higher. An increase can also be recorded in humans by means of transcutaneous PaO2 measurements. In proctology, we view the indication of rectal insufflation to be valid for colitis. The present report covers initial results and experience: a further short report on the possibility of treating hepatitis in the same way will be following.

Nanoindentation studies of full and empty viral capsids and the effects of capsid protein mutations on elasticity and strength.

The elastic properties of capsids of the cowpea chlorotic mottle virus have been examined at pH 4.8 by nanoindentation measurements with an atomic force microscope. Studies have been carried out on WT capsids, both empty and containing the RNA genome, and on full capsids of a salt-stable mutant and empty capsids of the subE mutant. Full capsids resisted indentation more than empty capsids, but all of the capsids were highly elastic. There was an initial reversible linear regime that persisted up to indentations varying between 20% and 30% of the diameter and applied forces of 0.6-1.0 nN; it was followed by a steep drop in force that is associated with irreversible deformation. A single point mutation in the capsid protein increased the capsid stiffness. The experiments are compared with calculations by finite element analysis of the deformation of a homogeneous elastic thick shell. These calculations capture the features of the reversible indentation region and allow Young's moduli and relative strengths to be estimated for the empty capsids.

[Total mineral analysis of fracture callus in fracture healing--an animal experiment study]. / Gesamtmineralanalyse des Frakturkallus während der Knochenbruchheilung--tierexperimentelle Untersuchung.

The total mineral contents in the fracture callus was determined quantitatively on the fracture model of the closed fracture of the lower leg and the secondary bone fracture healing in rabbits with the technique by Cameron and Sörenson (1963) on the 7th, 14th, 21st, 28th, 42nd, 70th, 128th, and 168th day after the fracture. The total mineral contents in the fracture callus corresponds to the normal value of the non-traumatised tibia from the 42nd day after the fracture. The absorption measuring is a fast practicable and well reproducible method for the follow-up of the fracture healing.

[Significance and evaluation of gingival and bony pockets]. / Bedeutung und Beurteilung von Zahnfleisch- und Knochentaschen.

The reproducibility of measurements of gingival pocket depth was tested on a total of 200 patients and assessed by statistical analysis. Significantly differing values were observed only in the region of the upper molars, whereas consistent values were found in all the other regions. The measurement of pocket depth is an easy-to-determine reproducible parameter in periodontal diagnostics. A gross information about the presence and depth of intrabony pockets cannot be obtained from clinical values for pocket depth.

[Angiographic demonstration of the medullary space and callus vessels during secondary bone fracture healing; animal experiments]. / Angiographische Darstellung der Markraum- und Kallusgefässe während der sekundären Knochenbruchheilung--tierexperimentelle Untersuchungen.

The artery nutritia ruptured in a closed transverse fracture of the tibia in 86% during the fracture trauma. Because blood vessels go through between the periost and the metaphysial medullary space it does not come to an ischemia in the medullary space of the distal fragment. The periosteal and paraosseous revascularisation increased with the extension of the fragment shifting. The artery nutritia is recombinated spontaneously in the complete cross section after 10 weeks. A good demonstration of the callus vessels is attainable by lumbar aortography with barium sulphate.