Osteoinductive implants: the mise-en-scène for drug-bearing biomimetic coatings

In orthopaedic and dental implantology, novel tools and techniques are being sought to improve the regeneration of bone tissue. Numerous attempts have been made to enhance the osteoconductivity of titanium prostheses, including modifications in their surface properties and coating with layers of calcium phosphate. The technique whereby such layers are produced has recently undergone a revolutionary change, which has had profound consequences for their potential to serve as drug-carrier systems. Hitherto, calcium phosphate layers were deposited upon the surfaces of metal implants under highly unphysiological physical conditions, which precluded the incorporation of proteinaceous osteoinductive drugs. These agents could only be adsorbed, superficially, upon preformed layers. Such superficially adsorbed molecules are released too rapidly within a biological milieu to be effective in their osteoinductive capacity. Now, it is possible to deposit calcium phosphate layers under physiological conditions of temperature and pH by the so-called biomimetic process, during which bioactive agents can be coprecipitated. Since these molecules are integrated into the inorganic latticework, they are released gradually in vivo as the layer undergoes degradation. This feature enhances the capacity of these coatings to act as a carrier system for osteogenic agents.

Whole-body vibration exposure study in U.S. railroad locomotives--an ergonomic risk assessment

Whole-body vibration exposure of locomotive engineers and the vibration attenuation of seats in 22 U.S. locomotives (built between 1959 and 2000) was studied during normal revenue service and following international measurement guidelines. Triaxial vibration measurements (duration mean 155 min, range 84-383 min) on the seat and on the floor were compared. In addition to the basic vibration evaluation (aw rms), the vector sum (av), the maximum transient vibration value (MTVV/aw), the vibration dose value (VDV/(aw T1/4)), and the vibration seat effective transmissibility factor (SEAT) were calculated. The power spectral densities are also reported. The mean basic vibration level (aw rms) was for the fore-aft axis x = 0.18 m/sec2, the lateral axis y = 0.28 m/sec2, and the vertical axis z = 0.32 m/sec2. The mean vector sum was 0.59 m/sec2 (range 0.27 to 1.44). The crest factors were generally at or above 9 in the horizontal and vertical axis. The mean MTVV/aw was 5.3 (x), 5.1 (y), and 4.8 (z), and the VDV/(aw T1/4) values ranged from 1.32 to 2.3 (x-axis), 1.33 to 1.7 (y-axis), and 1.38 to 1.86 (z-axis), generally indicating high levels of shocks. The mean seat transmissibility factor (SEAT) was 1.4 (x) and 1.2 (y) and 1 (z), demonstrating a general ineffectiveness of any of the seat suspension systems. In conclusion, these data indicate that locomotive rides are characterized by relatively high shock content (acceleration peaks) of the vibration signal in all directions. Locomotive vertical and lateral vibrations are similar, which appears to be characteristic for rail vehicles compared with many road/off-road vehicles. Tested locomotive cab seats currently in use (new or old) appear inadequate to reduce potentially harmful vibration and shocks transmitted to the seated operator, and older seats particularly lack basic ergonomic features regarding adjustability and postural support.

Modeling and Vibration Suppression for Telescopic Systems of Structural Members with Clearance

Telescopic systems of structural members with clearance are found in many applications, e.g., mobile cranes, rack feeders, fork lifters, stacker cranes (see Figure 1). Operating these machines, undesirable vibrations may reduce the performance and increase safety problems. Therefore, this contribution has the aim to reduce these harmful vibrations. For a better understanding, the dynamic behaviour of these constructions is analysed. The main interest is the overlapping area of each two sections of the above described systems (see markings in Figure 1) which is investigated by measurements and by computations. A test rig is constructed to determine the dynamic behaviour by measuring fundamental vibrations and higher frequent oscillations, damping coefficients, special appearances and more. For an appropriate physical model, the governing boundary value problem is derived by applying Hamilton’s principle and a classical discretisation procedure is used to generate a coupled system of nonlinear ordinary differential equations as the corresponding truncated mathematical model. On the basis of this model, a controller concept for preventing harmful vibrations is developed.

Electro-oxidation of Au(1 1 1) in contact with aqueous electrolytes: New insight from in situ vibration spectroscopy

We carried out a comprehensive study of Au(1 1 1) oxidation–reduction in the presence of (hydrogen-) sulfate ions on ideally smooth and stepped Au(S)[n(1 1 1)-(1 1 1)] single crystal electrodes using cyclic voltammetry, in situ scanning tunneling microscopy (STM) and vibration spectroscopy, such as surface-enhanced infrared absorption spectroscopy (SEIRAS) and shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). Surface structure changes and the role of surface defects in the potential regions of double layer charging and gold oxidation/reduction are discussed based on cyclic voltammetry and in situ STM data. SEIRAS and SHINERS provide complementary information on the chemical nature of adsorbates. In particular, the potential-dependent formation and stability ranges of adsorbed sulfate, hydroxide-species and of gold surface oxide could be resolved in detail. Based on our experimental observations, we proposed new and extended mechanisms of gold surface oxidation and reduction in 1.0 M H2SO4 and 1.0 M Na2SO4.

Acute effects of stochastic resonance whole body vibration

AIM: To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. METHODS: Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. RESULTS: Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m2). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover, muscle relaxation after verum SR-WBV was higher than after sham SR-WBV (P < 0.05). CONCLUSION: Verum SR-WBV stimulated musculoskeletal activity in young healthy individuals while cardiovascular activation was low. Training of musculoskeletal capacity and immediate increase in musculoskeletal relaxation are potential mediators of pain reduction in preventive trials.

Analysis of polygonal cracking patterns in chloride-bearing terrains on Mars: Indicators of ancient playa settings

The ancient southern highlands on Mars (~3.5 Gyr old) contain > 600 regions that display spectral evidence in the infrared for the presence of chloride-bearing materials. Many of these locations were previously reported to display polygonal cracking patterns. We studied more than 80 of the chloride-bearing terrains using high-resolution (0.25-0.5 m/pixel) images, as well as near-infrared spectral data, to characterize the surface textures and the associated cracking patterns and mineralogies. Our study indicates that ~75% of the studied locations display polygonal cracks that resemble desiccation cracks, while some resemble salt expansion/thrust polygons. Furthermore, we detect, spectrally, the presence of smectites in association with ~30% of the studied fractured terrains. We note that smectites are a special class of swelling clay minerals that can induce formation of large desiccation cracks. As such, we suggest that the cracking patterns are indicative of the presence of smectite phyllosilicates even in the absence of spectral confirmation. Our results suggest that many chloride-bearing terrains have a lacustrine origin and a geologic setting similar to playas on Earth. Such locations would have contained ephemeral lakes that may have undergone repeated cycles of desiccation and recharging by a near-surface fluctuating water table in order to account for the salt-phyllosilicates associations. These results have notable implications for the ancient hydrology of Mars. We propose that the morphologies and sizes of the polygonal cracks can be used as paleoenvironmental, as well as lithological, indicators that could be helpful in planning future missions.

Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

We assessed the suitability of the radiolanthanide 155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods 155Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~ 1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. 155 Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules – a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) – were radiolabeled with 155 Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. Results The total yield of the two-step separation process of 155 Tb was 86%. 155 Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The 155 Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (> 95%). 155 Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of 155 Tb-DOTATATE and 155 Tb-MD, respectively. The relatively long physical half-life of 155 Tb matched in particular the biological half-lives of 155 Tb-cm09 and 155 Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions The radiolanthanide 155 Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β--emitting radiolanthanides 177Lu, 161 Tb, 166Ho, and the pseudo-radiolanthanide 90Y.

Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy

Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.

Tailoring surface nanostructures on polyaryletherketones for load-bearing implants

High-performance thermoplastics including polyetheretherketone (PEEK) are key biomaterials for load-bearing implants. Plasma treatment of implants surfaces has been shown to chemically activate its surface, which is a prerequisite to achieve proper cell attachment. Oxygen plasma treatment of PEEK films results in very reproducible surface nanostructures and has been reported in the literature. Our goal is to apply the plasma treatment to another promising polymer, polyetherketoneketone (PEKK), and compare its characteristics to the ones of PEEK. Oxygen plasma treatments of plasma powers between 25 and 150 W were applied on 60 μm-thick PEKK and 100 μm-thick PEEK films. Analysis of the nanostructures by atomic force microscopy showed that the roughness increased and island density decreased with plasma power for both PEKK and PEEK films correlating with contact angle values without affecting bulk properties of the used films. Thermal analysis of the plasma-treated films shows that the plasma treatment does not change the bulk properties of the PEKK and PEEK films.

Clutter elimination for deep clinical optoacoustic imaging using localised vibration tagging (LOVIT)

This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering. In this study we demonstrate that signals of interest can be distinguished from clutter by tagging them at the place of origin with localised tissue vibration induced by the acoustic radiation force in a focused ultrasonic beam. We show phantom results where this technique allowed almost full clutter elimination and thus strongly improved contrast for deep imaging. Localised vibration tagging by means of acoustic radiation force is especially promising for integration into ultrasound systems that already have implemented radiation force elastography.

Boron-Bearing Kornerupine from Fiskenaesset, West Greenland: A Reexamination of Specimens from the Type Locality

In 1884, Lorenzen proposed the formula MgAI2SiO6 for his new mineral kornerupine from Fiskenæsset and did not suspect it to contain boron. Lacroix and de Gramont (1919) reported boron in Fiskenæsset kornerupine, while Herd (1973) found none. New analyses (ion microprobe mass analyser and spectrophotometric) of kornerupine in three specimens from the type locality, including the specimens analysed by Lorenzen and Herd, indicate the presence of boron in all three, in amounts ranging from 0.50 to 1.44 wt.% B203, e.g. (Li0.04 Na0.01 Ca0.01) (Mg3.49 Mn0.01 Fe0.17 Ti0.01 Al5.64)Σ9.30 (Si3.67 Al1.02 B0.31)Σ5 O21 (OH0.99 F0.01) for Lorenzen's specimen. Textures and chemical compositions suggest that kornerupine crystallized in equilibrium in the following assemblages, all with anorthite (An 92-95) and phlogopite (XFe = atomic Fe/(Fe + Mg) = 0.028-0.035): (1) kornerupine (0.045)-gedrite (0.067); (2) kornerupine (0.038-0.050)-sapphirine (0.032-0.035); and (3) kornerupine (0.050)-hornblende. Fluorine contents of kornerupine range from 0.01 to 0.06%, of phlogopite, from 0.09 to 0.10%. In the first assemblage, sapphirine (0.040) and corundum are enclosed in radiating bundles of kornerupine; additionally sapphirine, corundum, and/or gedrite occur with chlorite and pinite (cordierite?) as breakdown products of kornerupine. Kornerupine may have formed by reactions such as: gedrite + sapphirine + corundum + B203 (in solution) + H20 = kornerupine + anorthite + Na-phlogopite under conditions of the granulite facies. Boron for kornerupine formation was most likely remobilized by hydrous fluids from metasedimentary rocks occurring along the upper contact of the Fiskenæsset gabbro-anorthosite complex with amphibolite.

Atlas-based Segmentation of Tumor-bearing Brain Images

In diagnostic neuroradiology as well as in radiation oncology and neurosurgery, there is an increasing demand for accurate segmentation of tumor-bearing brain images. Atlas-based segmentation is an appealing automatic technique thanks to its robustness and versatility. However, atlas-based segmentation of tumor-bearing brain images is challenging due to the confounding effects of the tumor in the patient image. In this article, we provide a brief background on brain tumor imaging and introduce the clinical perspective, before we categorize and review the state of the art in the current literature on atlas-based segmentation for tumor-bearing brain images. We also present selected methods and results from our own research in more detail. Finally, we conclude with a short summary and look at new developments in the field, including requirements for future routine clinical use.