Ice premelting during differential scanning calorimetry

Premelting at the surface of ice crystals is caused by factors such as temperature, radius of curvature, and solute composition. When polycrystalline ice samples are warmed from well below the equilibrium melting point, surface melting may begin at temperatures as low as -15 degrees C. However, it has been reported (. Biophys. J. 65:1853-1865) that when polycrystalline ice was warmed in a differential scanning calorimetry (DSC) pan, melting began at about -50 degrees C, this extreme behavior being attributed to short-range forces. We show that there is no driving force for such premelting, and that for pure water samples in DSC pans curvature effects will cause premelting typically at just a few degrees below the equilibrium melting point. We also show that the rate of warming affects the slope of the DSC baseline and that this might be incorrectly interpreted as an endotherm. The work has consequences for DSC operators who use water as a standard in systems where subfreezing runs are important.     

Intrarectal transmission of simian immunodeficiency virus in rhesus macaques: selective amplification and host responses to transient or persistent viremia.

Intrarectal simian immunodeficiency virus (SIV) infection in rhesus macaques is a model for sexual transmission of primate retroviruses. Phylogenetic studies on envelope gene sequences that were present in blood following intrarectal SIV inoculation provided evidence for selective amplification of a subset of viruses present in the inoculum and defined one amino acid sequence uniquely associated with intrarectal infection. Both persistent and transient viremia states were observed after intrarectal infection. Immune responses in persistently infected animals accounted for slower rates of disease progression despite the presence of highly pathogenic viruses that were documented by transfusion studies. Transient viremia elicited protective immunity against subsequent intrarectal virus challenge but did not protect against intravenous virus challenge. Transient viremia usually but not always led to self-limiting infection. In one animal, we documented a relapse to active viremia long after the initial transient viremia. SIV transmission across mucosal barriers affects pathogenesis in the short term by limiting the types of viruses established in the host and in the longer term by establishing host responses that slow disease progression despite the presence of highly pathogenic viruses in blood.     

Creation of an in vitro biomechanical model of the trachea using rapid prototyping

Previous in vitro models of the airways are either rigid or, if flexible, have not matched in vivo compliance characteristics. Rapid prototyping provides a quickly evolving approach that can be used to directly produce in vitro airway models using either rigid or flexible polymers. The objective of this study was to use rapid prototyping to directly produce a flexible hollow model that matches the biomechanical compliance of the trachea. The airway model consisted of a previously developed characteristic mouth–throat region, the trachea, and a portion of the main bronchi. Compliance of the tracheal region was known from a previous in vivo imaging study that reported cross-sectional areas over a range of internal pressures. The compliance of the tracheal region was matched to the in vivo data for a specific flexible resin by iteratively selecting the thicknesses and other dimensions of tracheal wall components. Seven iterative models were produced and illustrated highly non-linear expansion consisting of initial rapid size increase, a transition region, and continued slower size increase as pressure was increased. Thickness of the esophageal interface membrane and initial trachea indention were identified as key parameters with the final model correctly predicting all phases of expansion within a value of 5% of the in vivo data. Applications of the current biomechanical model are related to endotracheal intubation and include determination of effective mucus suctioning and evaluation of cuff sealing with respect to gases and secretions.     

A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative

Background

Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.

Methods

This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.

Results

No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).

Conclusion

Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.

Trial registration

Nederlands Trial Register NTR1395

     

The role of surfactant protein D in the colonisation of the respiratory tract and onset of bacteraemia during pneumococcal pneumonia

We have shown previously that surfactant protein D (SP-D) binds and agglutinates Streptococcus pneumoniae in vitro. In this study, the role of SP-D in innate immunity against S. pneumoniae was investigated in vivo, by comparing the outcome of intranasal infection in surfactant protein D deficient (SP-D-/-) to wildtype mice (SP-D+/+). Deficiency of SP-D was associated with enhanced colonisation and infection of the upper and lower respiratory tract and earlier onset and longer persistence of bacteraemia. Recruitment of neutrophils to inflammatory sites in the lung was similar in both strains mice in the first 24 hrs post-infection, but different by 48 hrs. T cell influx was greatly enhanced in SP-D-/- mice as compared to SP-D+/+ mice. Our data provides evidence that SP-D has a significant role to play in the clearance of pneumococci during the early stages of infection in both pulmonary sites and blood.     

A common reference population from four European Holstein populations increases reliability of genomic predictions

Background

Size of the reference population and reliability of phenotypes are crucial factors influencing the reliability of genomic predictions. It is therefore useful to combine closely related populations. Increased accuracies of genomic predictions depend on the number of individuals added to the reference population, the reliability of their phenotypes, and the relatedness of the populations that are combined.

Methods

This paper assesses the increase in reliability achieved when combining four Holstein reference populations of 4000 bulls each, from European breeding organizations, i.e. UNCEIA (France), VikingGenetics (Denmark, Sweden, Finland), DHV-VIT (Germany) and CRV (The Netherlands, Flanders). Each partner validated its own bulls using their national reference data and the combined data, respectively.

Results

Combining the data significantly increased the reliability of genomic predictions for bulls in all four populations. Reliabilities increased by 10%, compared to reliabilities obtained with national reference populations alone, when they were averaged over countries and the traits evaluated. For different traits and countries, the increase in reliability ranged from 2% to 19%.

Conclusions

Genomic selection programs benefit greatly from combining data from several closely related populations into a single large reference population.     

Validating CFD predictions of respiratory aerosol deposition: effects of upstream transition and turbulence

A number of computational fluid dynamics (CFD) studies have explored local deposition patterns of inhaled aerosols in the respiratory tract. These studies have highlighted the effects of multiple physiologic, geometric, and particle characteristics on deposition. However, very few studies have reported local or sub-branch quantitative comparisons to in vitro particle deposition data. The objective of this study is to numerically investigate the effects of transition and turbulence on highly localized particle deposition in a respiratory double bifurcation model in order to quantitatively validate CFD results. To perform the validations, local comparisons have been made to a specific in vitro case study of 10 microm particles depositing in a model of respiratory generations G3-G5. To achieve this objective, two geometric cases have been considered. The first case includes only the double bifurcation model. The second case includes a portion of the experimental particle delivery geometry, where transitional flow is expected. To evaluate the effectiveness of two-equation turbulence models in this system, the flow field solutions have been computed using laminar, standard k-omega, and low Reynolds number (LRN) k-omega approximations. Results indicate that even though the Reynolds number remained below the critical limit required for full turbulence, transition and turbulence have a significant impact on the flow field and local particle deposition patterns. For the experimental case considered, turbulence impacted the local deposition of 10 microm particles primarily by influencing the initial velocity and particle profiles. As such, both the laminar and LRN k-omega flow models provided good local quantitative matches to the in vitro deposition data, provided that the correct initial particle profile was specified. Implications of this study include the need for local quantitative validations of particle deposition results, the importance of correct inlet conditions, and the need to consider upstream effects in experimental and computational studies of the respiratory tract. Applications of these results to realistic respiratory geometries will require consideration on upstream flow conditions in the lung, transient flow, and intermittent turbulent structures.     

Comparison of blood particle deposition models for non-parallel flow domains

Adhesions of monocytes and platelets to a vascular surface, particularly in regions of flow stagnation, recirculation, and reattachment, are a significant initial event in a broad spectrum of particle-wall interactions that significantly influence the formation of stenotic lesions and mural thrombi. A number of approximations are available for the simulation of both monocyte and platelet interactions with the vascular surface. For the simulation of blood particle adhesion, this study hypothesizes that: (a) the discrete element approach, which accounts for finite particle size and inertia, is advantageous in the context of non-parallel flow domains including stagnation, recirculation, and reattachment; and (b) the likelihood for particle deposition may be effectively approximated as being non-linearly proportional to local particle concentration, residence time, and wall proximity. Models such as wall shear stress correlations, the multicomponent mixture approach, and Lagrangian particle tracking with and without hydrodynamic particle-wall interactions were evaluated. Quantitative performance of the selected models was established by comparisons to available experimental data sets for non-parallel axisymmetric suspension flows of monocytes and platelets. Factors including the convective-diffusive transport of particles, finite particle size and inertia, as well as near-wall hydrodynamic interactions were found to significantly influence blood particle deposition. Of the models studied, the near-wall residence time approach was found to be a particularly effective indicator for the deposition of monocytes (r2=0.74) and platelets (r2=0.57), given that nano-scale physical and biochemical effects must be greatly approximated in computational simulations involving relatively large-scale geometries and complex flow fields.     

Numerical simulation of wall shear stress conditions and platelet localization in realistic end-to-side arterial anastomoses

Research studies over the last three decades have established that hemodynamic interactions with the vascular surface as well as surgical injury are inciting mechanisms capable of eliciting distal anastomotic intimal hyperplasia (IH) and ultimate bypass graft failure. While abnormal wall shear stress (WSS) conditions have been widely shown to affect vascular biology and arterial wall self-regulation, the near-wall localization of critical blood particles by convection and diffusion may also play a significant role in IH development. It is hypothesized that locations of elevated platelet interactions with reactive or activated vascular surfaces, due to injury or endothelial dysfunction, are highly susceptible to IH initialization and progression. In an effort to assess the potential role of platelet-wall interactions, experimentally validated particle-hemodynamic simulations have been conducted for two commonly implemented end-to-side anastomotic configurations, with and without proximal outflow. Specifically, sites of significant particle interactions with the vascular surface have been identified by a novel near-wall residence time (NWRT) model for platelets, which includes shear stress-based factors for platelet activation as well as endothelial cell expression of thrombogenic and anti-thrombogenic compounds. Results indicate that the composite NWRT model for platelet-wall interactions effectively captures a reported shift in significant IH formation from the arterial floor of a relatively high-angle (30 deg) graft with no proximal outflow to the graft hood of a low-angle graft (10 deg) with 20% proximal outflow. In contrast, other WSS-based hemodynamic parameters did not identify the observed system-dependent shift in IH formation. However, large variations in WSS-vector magnitude and direction, as encapsulated by the WSS-gradient and WSS-angle-gradient parameters, were consistently observed along the IH-prone suture-line region. Of the multiple hemodynamic factors capable of eliciting a hyperplastic response at the cellular level, results of this study indicate the potential significance of platelet-wall interactions coinciding with regions of low WSS in the development of IH.     

Mitochondrial control-region sequences in two shorebird species, the turnstone and the dunlin, and their utility in population genetic studies

We determined the mitochondrial control-region sequences of five turnstones (Arenaria interpres) and three dunlins (Calidris alpina). Comparisons revealed that the central part (part II) is conserved relative to much more variable parts at the beginning (part I) and the end (part III). This pattern of sequence conservation is also found in the control regions of other vertebrates. The average sequence divergence between turnstone and dunlin was 21.8% for part I, 7.5% for part II, and 29.5% for part III. Within-species sequence divergence over the entire control region was much lower, at 0.9% for turnstones and 2.0% for dunlins. In both shorebird species, part III contains a repetitive sequence composed only of A and C nucleotides, which has not been found in the control regions of other birds. A survey of the part I sequences of 25 turnstones and 25 dunlins sampled around the world revealed that these species have very different population genetic structures. Dunlins are not only much more differentiated in their sequences but also have a strongly subdivided population genetic structure. Pleistocene vicariant events combined with strong natal philopatry and high mutation rates of the sequences are likely responsible for this population genetic subdivision. Conversely, part I sequences of turnstones are weakly differentiated and are geographically unstructured. We argue that this is not the result of global gene flow but that, instead turnstones have recently expanded from a refugial population that was bottlenecked.