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Biomedical subjects

S Auer

Publications and source records attributed to S Auer.

18 recordsLinked to original sources

Breakdown of classical nucleation theory near isostructural phase transitions.

We report simulations of crystal nucleation in binary mixtures of hard spherical colloids with a size ratio of 1:10. The stable crystal phase of this system can be either dense or expanded. We find that, in the vicinity of the solid-solid critical point where the crystallites are highly compressible, small crystal nuclei are less dense than large nuclei. This phenomenon cannot be accounted for by either classical nucleation theory or by the Gibbsian droplet model. We argue that the observed behavior is due to the surface stress of the crystal nuclei. The observed effect highlights a general deficiency of the most frequently used thermodynamic theories for crystal nucleation. Surface stress should lead to an experimentally observable expansion of crystal nuclei of colloids with short-ranged attraction and of globular proteins.

Journal Article↗

Onset of heterogeneous crystal nucleation in colloidal suspensions.

The addition of small 'seed' particles to a supersaturated solution can greatly increase the rate at which crystals nucleate. This process is understood, at least qualitatively, when the seed has the same structure as the crystal that it spawns. However, the microscopic mechanism of seeding by a 'foreign' substance is not well understood. Here we report numerical simulations of colloidal crystallization seeded by foreign objects. We perform Monte Carlo simulations to study how smooth spherical seeds of various sizes affect crystallization in a suspension of hard colloidal particles. We compute the free-energy barrier associated with crystal nucleation. A low barrier implies that nucleation is easy. We find that to be effective crystallization promoters, the seed particles need to exceed a well-defined minimum size. Just above this size, seed particles act as crystallization 'catalysts' as newly formed crystallites detach from the seed. In contrast, larger seed particles remain covered by the crystallites that they spawn. This phenomenon should be experimentally observable and can have important consequences for the control of the resulting crystal size distribution.

Journal Article↗

Numerical prediction of absolute crystallization rates in hard-sphere colloids.

Special computational techniques are required to compute absolute crystal nucleation rates of colloidal suspensions. Using crystal nucleation of hard-sphere colloids as an example, we describe in some detail the novel computational tools that are needed to perform such calculations. In particular, we focus on the definition of appropriate order parameters that distinguish liquid from crystal, and on techniques to compute the kinetic prefactor that enters in the expression for the nucleation rate. In addition, we discuss the relation between simulation results and theoretical predictions based on classical nucleation theory.

Journal Article↗

Line tension controls wall-induced crystal nucleation in hard-sphere colloids.

We report on a numerical study of the effect of a smooth, hard wall on the crystallization of hard-sphere colloids. We find that the presence of the wall drastically lowers the barrier for crystal nucleation, but it does not eliminate it. Crystal nucleation becomes noticeable at pressures that are some 5% above the coexistence value. The first particles to crystallize on the wall form a (111) plane. Initially, this crystallite grows laterally, rather than in the third dimension. The free energy of the critical crystal nucleus on the wall is about 2 orders of magnitudes lower than in the bulk. Analysis of the numerical data indicates that, at coexistence, the (111) plane is at the threshold of wetting the wall. The nucleation barrier is dominated by line tension.

Journal Article↗

Phase behavior and crystallization kinetics of poly-12-hydroxystearic-coated polymethylmethacrylate colloids.

Polymethylmethacrylate (PMMA) colloids sterically stabilized by a layer of chemically grafted poly-12-hydroxystearic (PHSA) are widely used in experiments as model hard spheres. However, due to the coating, the interaction between particles is slightly soft. Here we report a numerical study of the effect of the PHSA coating on the phase behavior and crystallization kinetics of PMMA colloids based on parameters determined from surface-force measurements on PHSA-PMMA-coated mica surfaces [B. A. de L. Costello and P. F. Luckham, J. Colloid Interface Sci. 156, 72 (1993); B. A. de L. Costello et al., Langmuir 8, 464 (1992)]. We find that the core volume fraction of particles at freezing measured by Pusey and van Megen [Nature 320, 340 (1986)] can only be reproduced by using a thickness of the PHSA layer that is considerably larger than literature values. This may indicate that the particles are in fact slightly charged. Compared to perfect hard spheres, the crystallization rate in these slightly soft particles was found to be increased by about two orders of magnitudes.

Journal Article↗

[Central case management in surgery].

Up to now, in most surgical departments there has been no central patient management coordinating the admission, the diagnostic work-up, and the surgical procedures of patients with the resources available in the hospital. In future, however, it will be essential for surgical departments to establish such a central patient management, not only in view of the importance of patient-oriented medicine but also considering the planned introduction of diagnosis related groups. A central patient management will reduce preoperative and overall length of stay through adequate organisation and communication structures. In addition, a central patient management will make optimal use of the available resources in terms of operation rooms and hospital beds. In this article, we will present our basic concept of a central patient management in a surgical university department.

Diagnosis↗

[Central patient management in surgery].

Up to now, in most surgical departments there has been no central patient management coordinating the admission, the diagnostic work-up, and the surgical procedures of patients with the resources available in the hospital. In future, however, it will be essential for surgical departments to establish such a central patient management, not only in view of the importance of patient-oriented medicine but also considering the planned introduction of diagnosis related groups. A central patient management will reduce preoperative and overall length of stay through adequate organisation and communication structures. In addition, a central patient management will make optimal use of the available resources in terms of operation rooms and hospital beds. In this article, we will present our basic concept of a central patient management in a surgical university department.

Diagnosis-Related Groups↗

Suppression of crystal nucleation in polydisperse colloids due to increase of the surface free energy.

The formation of small crystallites is governed by two competing factors: the free energy gained upon transferring constituent atoms, molecules or colloidal particles from the metastable liquid to the more stable solid, and the free energy needed to create the surface area of the crystallite. Because the ratio of surface area to bulk is large for small particles, small crystallites dissolve spontaneously under conditions where larger crystallites are stable and macroscopic crystal growth occurs only if spontaneously formed crystallites exceed a critical minimum size. On theoretical grounds, the probability of forming such critical crystal nuclei is expected to increase rapidly with supersaturation. However, experiments show that the rate of crystal nucleation in many systems goes through a maximum as the supersaturation is increased. It is commonly assumed that the nucleation rate peaks because, even though the probability of forming critical nuclei increases with increasing concentration, the rate of growth of such nuclei decreases. Here we report simulations of crystal nucleation in suspensions of colloidal spheres with varying size distributions that show that the probability that critical nuclei will form itself goes through a maximum as the supersaturation is increased. We find that this effect, which is strongest for systems with the broadest particle size distribution, results from an increase with supersaturation of the solid-liquid interfacial free energy. The magnitude of this effect suggests that vitrification at high supersaturations should yield colloidal glasses that are truly amorphous, rather than nano-crystalline.

Journal Article↗

Prediction of absolute crystal-nucleation rate in hard-sphere colloids.

Crystal nucleation is a much-studied phenomenon, yet the rate at which it occurs remains difficult to predict. Small crystal nuclei form spontaneously in supersaturated solutions, but unless their size exceeds a critical value--the so-called critical nucleus--they will re-dissolve rather than grow. It is this rate-limiting step that has proved difficult to probe experimentally. The crystal nucleation rate depends on Pcrit, the (very small) probability that a critical nucleus forms spontaneously, and on a kinetic factor (kappa) that measures the rate at which critical nuclei subsequently grow. Given the absence of a priori knowledge of either quantity, classical nucleation theory is commonly used to analyse crystal nucleation experiments, with the unconstrained parameters adjusted to fit the observations. This approach yields no 'first principles' prediction of absolute nucleation rates. Here we approach the problem from a different angle, simulating the nucleation process in a suspension of hard colloidal spheres, to obtain quantitative numerical predictions of the crystal nucleation rate. We find large discrepancies between the computed nucleation rates and those deduced from experiments: the best experimental estimates of Pcrit seem to be too large by several orders of magnitude.

Journal Article↗

Progression of Alzheimer's disease: variability and consistency: ontogenic models, their applicability and relevance.

Much has been learned about the clinical symptomatology of Alzheimer's disease (AD) and ontogenic reciprocal relationships in the past few decades. It is now possible to describe and verify inexorable symptomatic sequences and corresponding temporal relationships. It is also possible to identify more variable symptoms in AD. Ontogenic models can be useful in providing a clearer understanding of the nature of AD symptomatology in terms of both consistency and variability. These models can also be informative in explicating the management needs of AD patients and the treatment possibilities of AD symptoms as well as the etiology of variability in AD symptoms.

Activities of Daily Living↗

The GDS/FAST staging system.

Staging methodologies are an essential tool in the assessment of disease severity in progressive dementing illness. Several different instruments have been developed for this purpose. One of the most widely used methodologies is the Global Deterioration Scale/Functional Assessment Staging (GDS/FAST) system. This system has been studied extensively and proven to be reliable and valid for staging dementia in Alzheimer's disease (AD) in diverse settings. One of the major advantages of this system is that it spans, demarcates, and describes the entire course of normal aging and progressive AD until the final substages of the disease process. Other advantages include: (a) greatly enhanced ability to track the longitudinal course of AD, (b) improved clinicopathologic observations of AD interrelationships, and (c) enhanced diagnostic, differential diagnostic, and prognostic information. This article presents a brief overview of the GDS/FAST staging system.

Alzheimer Disease↗

The use of Baypamun N in crowding-associated infectious respiratory disease: efficacy of Baypamun N (freeze dried product) in 2-week-old veal calves.

The efficacy of an immunomodulator, Baypamun N, was tested in 10-20-day-old veal calves from different farms, which were exposed to stress by transport and commingling (crowding). Verum and placebo animals (n = 50, each group) received three intramuscular injections of the investigational products (days 0, 2, 4) starting the day of arrival on the farm. Data from 49 calves in each group could be used for statistical evaluation. The incidence of acute bovine respiratory disease was anticipated to be high during the first 2 weeks after arrival on farm based on experience from other years. The clinical scores in the Baypamun N group were significantly reduced by 52.7% (P < 0.001) compared to the placebo group. The number of antibiotic treatments was significantly reduced by 53.8% (P < 0.001) in the Baypamun N group. Of the calves treated with Baypamun N, 51.02% remained untreated with antibiotics during the first 2 weeks after arrival on the farm compared with only 16.3% of the placebo treated control calves (P < 0.001).

Adjuvants, Immunologic↗

A gE deleted infectious bovine rhinotracheitis marker vaccine for use in improved bovine herpesvirus 1 control programs.

Based on a glycoprotein E (gE) deleted bovine herpesvirus 1 (BHV1) strain (Kaashoek et al., 1994) a killed virus as well as a modified live virus marker vaccine have been developed that allow differentiation between immunized and BHV1 infected cattle. Safety and efficacy of both vaccines were tested extensively following the current European Union (EU) requirements for the development of bovine vaccines. The minimum vaccine dose, vaccination regimen, route of administration and duration of immunity were evaluated for both vaccines in comprehensive vaccination/challenge trials in cattle. The most potent adjuvant formulation for the killed virus vaccine was also selected by experimental challenge infections. For the modified live virus marker vaccine it could be demonstrated that maternally derived BHV1 specific antibodies did not interfere with vaccination. Safety could be demonstrated for both the killed virus and the modified live virus vaccine in all target animal categories including veal calves, beef cattle, bulls, heifers and dairy cattle, including pregnant animals.

Animals↗

Overview of methodologic issues for pharmacologic trials in mild, moderate, and severe Alzheimer's disease.

To address the issue of mild, moderate, and severe Alzheimer's disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them.

Activities of Daily Living↗

Dyphylline aerosol can induce bronchospasm in human asthmatics.

Dihydroxypropyl theophylline (dyphylline) was administered by aerosol in a single dose of 250 mg aerosolized over five minutes to two asthmatic volunteers and in a single dose of 375 mg aerosolized over ten minutes to two other asthmatic volunteers. Serial spirometry was then performed. Marked bronchospasm occurred within ten minutes in two of the subjects, and developed more slowly in another. One subject demonstrated no significant change. Aerosolized dyphylline solution was not an effective bronchodilator, using the methods described in this study.

Adult↗