Search

Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin malignancy, with Australia having the highest reported incidence in the world. There is currently a lack of consensus regarding optimal management of this disease., Methods: This was a retrospective audit conducted by reviewing existing medical records of MCC patients presenting to the Peter MacCallum Cancer Centre (PMCC) between 1980 and 2018. The primary endpoint was locoregional recurrence. The secondary endpoints were distant recurrence, disease-free survival (DFS) and overall survival (OS)., Results: A total of 533 patients were identified. Locoregional recurrence occurring at one, two and 5 years was 24, 31 and 32%, respectively. The estimated 5-year OS and DFS were 46% (95% Confidence Interval [CI] 41-51%) and 34% (95% CI 30-39%) respectively. Older age at diagnosis (hazard ratio [HR] per year = 1.07, 95% CI 1.06-1.07, p < 0.001), and larger primary tumour diameter (HR =1.16, 95% CI 1.03-1.31, p = 0.019) were associated with worse OS on multivariable analysis. Positive or negative histopathological margin status was not associated with OS or DFS differences in patients treated with post-operative radiotherapy., Conclusions: In our study, about a third of patients developed locoregional recurrence, distal recurrence or both, and there appears to be no change over the last four decades. If treated with adjuvant radiotherapy, there is no difference in OS or DFS with positive surgical margins. Findings should influence future guidelines., (© 2023. The Author(s).)

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely investigated and utilized as magnetic resonance imaging (MRI) contrast and therapy agents due to their large magnetic moments. Local field inhomogeneities caused by these high magnetic moments are used to generate T 2 contrast in clinical high-field MRI, resulting in signal loss (darker contrast). Here we present strong T 1 contrast enhancement (brighter contrast) from SPIONs (diameters from 11 nm to 22 nm) as observed in the ultra-low field (ULF) MRI at 0.13 mT. We have achieved a high longitudinal relaxivity for 18 nm SPION solutions, r 1  = 615 s -1 mM -1 , which is two orders of magnitude larger than typical commercial Gd-based T 1 contrast agents operating at high fields (1.5 T and 3 T). The significantly enhanced r 1 value at ultra-low fields is attributed to the coupling of proton spins with SPION magnetic fluctuations (Brownian and Néel) associated with a low frequency peak in the imaginary part of AC susceptibility (χ"). SPION-based T 1 -weighted ULF MRI has the advantages of enhanced signal, shorter imaging times, and iron-oxide-based nontoxic biocompatible agents. This approach shows promise to become a functional imaging technique, similar to PET, where low spatial resolution is compensated for by important functional information.

Background: Polyethylene liner dissociation is a rare but catastrophic event in total hip arthroplasty (THA), and certain implant designs are known to be at greater risk. Although the DePuy Pinnacle (Warsaw, IN, USA) modular acetabular construct has an excellent record of fixation and wear, an unexpectedly high number of liner dissociations has been noted., Questions/purposes: The purposes of this study were (1) to characterize the clinical parameters observed in a large group of patients who have experienced liner dissociations with the DePuy Pinnacle acetabular component; (2) to describe the radiographic findings in this group of patients; and (3) to calculate a minimum frequency of this complication., Methods: Since 2001, 23 patients with previously well-functioning THAs presented with sudden atraumatic polyethylene liner dissociation at four separate institutions. These THAs were performed between 2001 and 2013. Eight different arthroplasty specialists had performed the index hip arthroplasties using the DePuy Pinnacle acetabular component with a polyethylene liner. Polyethylene failures were evaluated for liner type and radiographic cup position. For three of the surgeons who contributed cases, institutional registries allowed the calculation of the number of components of this type that they used during the period in question, which provided a conservative estimate of the frequency of this type of failure., Results: All 23 liner failures occurred atraumatically in previously asymptomatic THAs at a mean of 48 months (range, 3-138 months). Patients characteristically reported a new and sudden onset of discomfort with audible, reproducible squeaking. Surgical inspection of dissociated liners demonstrated displacement of polyethylene with shearing of the peripheral locking tabs. Radiographic evaluation demonstrated that 14 cups were well positioned and nine cups were malpositioned outside the so-called safe zone. Conservative estimates of the frequency of this complication from the three surgeons' practices whose institutional registries allowed calculation of the lowest possible frequency were 0.32% (six of 1888), 0.77% (three of 391), and 0.82% (three of 367)., Conclusions: With this report of 23 additional liner dissociations, we suggest that surgeons should be aware of the problem and take extra precautions when using this implant to ensure locking mechanism integrity at the time of surgery. We caution that the frequency of liner dissociation may be higher than previously reported., Level of Evidence: Level IV, therapeutic study.

The present study investigated the influence of 3D multimodal visualization and learning rehearsal on memory recall. Participants (N = 175 college students ranging from 21 to 25 years) were assigned to different training conditions and rehearsal processes to learn a list of 14 terms associated with construction of a wood-frame house. They then completed a memory test determining their cognitive ability to free recall the definitions of the 14 studied terms immediately after training and rehearsal. The audiovisual modality training condition was associated with the highest accuracy, and the visual- and auditory-modality conditions with lower accuracy rates. The no-training condition indicated little learning acquisition. A statistically significant increase in performance accuracy for the audiovisual condition as a function of rehearsal suggested the relative importance of rehearsal strategies in 3D observational learning. Findings revealed the potential application of integrating virtual reality and cognitive sciences to enhance learning and teaching effectiveness.

We have developed a nuclear magnetic resonance (NMR) microcapillary probe for the detection of single magnetic microbeads. The geometry of the probe has been optimized so that the signal from the background water has a similar magnitude compared to the signal from the dephased water nearby a single magnetic bead within the probe detector coil. In addition, the RF field of the coil must be uniform within the effective range of the magnetic bead. Three different RF probes were tested in a 7 T (300 MHz) pulsed NMR spectrometer with sample volumes ranging from 5 nL down to 1 nL. The 1 nL probe had a single-shot signal-to-noise ratio (SNR) for pure water of 27 and a volume resolution that exhibits a 600-fold improvement over a conventional (5 mm tube) NMR probe with a sample volume of 18 μL. This allowed for the detection of a 1 μm magnetite/polystyrene bead (m=2×10(-14)Am(2)) with an estimated experimental SNR of 30. Simulations of the NMR spectra for the different coil geometries and positions of the bead within the coil were developed that include the B(0) shift near a single bead, the inhomogeneity of the coils, the local coil sensitivity, the skin effect of the coil conductor, and quantitated estimates of the proximity effect between coil windings., (Published by Elsevier Inc.)

Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed.

We present a 91 MHz surface acoustic wave resonator with integrated microfluidics that includes a flow focus, an expansion region, and a binning region in order to manipulate particle trajectories. We demonstrate the ability to change the position of the acoustic nodes by varying the electronic phase of one of the transducers relative to the other in a pseudo-static manner. The measurements were performed at room temperature with 3 μm diameter latex beads dispersed in a water-based solution. We demonstrate the dependence of nodal position on pseudo-static phase and show simultaneous control of 9 bead streams with spatial control of -0.058 μm/deg ± 0.001 μm/deg. As a consequence of changing the position of bead streams perpendicular to their flow direction, we also show that the integrated acoustic-microfluidic device can be used to change the trajectory of a bead stream towards a selected bin with an angular control of 0.008 deg/deg ± 0.000(2) deg/deg.

While chemically synthesized superparamagnetic microparticles have enabled much new research based on MRI tracking of magnetically labeled cells, signal-to-noise levels still limit the potential range of applications. Here it is shown how, through top-down microfabrication, contrast agent relaxivity can be increased several-fold, which should extend the sensitivity of such cell-tracking studies. Microfabricated agents can benefit from both higher magnetic moments and higher uniformity than their chemically synthesized counterparts, implying increased label visibility and more quantitative image analyses. To assess the performance of microfabricated micrometer-sized contrast agent particles, analytic models and numerical simulations are developed and tested against new microfabricated agents described in this article, as well as against results of previous imaging studies of traditional chemically synthesized microparticle agents. Experimental data showing signal effects of 500-nm thick, 2-μm diameter, gold-coated iron and gold-coated nickel disks verify the simulations. Additionally, it is suggested that measures of location better than the pixel resolution can be obtained and that these are aided using well-defined contrast agent particles achievable through microfabrication techniques., (Copyright © 2010 Wiley-Liss, Inc.)

The actin cytoskeleton controls cell shape, motility, as well as intracellular molecular trafficking. The ability to remotely manipulate actin is therefore highly desirable as a tool to probe and manipulate biological processes at the molecular level. We demonstrate actin manipulation by labeling actin filaments with superparamagnetic iron oxide particles (IOPs) and applying a uniform magnetic field to affect actin orientation, polymerization and gliding on myosin. We show for the first time magnetic manipulation of magnetizable actin filaments at the molecular level while gliding on a bed of myosin molecules and during polymerization. A model for the magnetic alignment and guiding mechanism is proposed based on the torque from the induced molecular anisotropy due to interactions between neighboring IOPs distributed along magnetically labeled actin molecules.

In recent years, biotechnology and biomedical research have benefited from the introduction of a variety of specialized nanoparticles whose well-defined, optically distinguishable signatures enable simultaneous tracking of numerous biological indicators. Unfortunately, equivalent multiplexing capabilities are largely absent in the field of magnetic resonance imaging (MRI). Comparable magnetic-resonance labels have generally been limited to relatively simple chemically synthesized superparamagnetic microparticles that are, to a large extent, indistinguishable from one another. Here we show how it is instead possible to use a top-down microfabrication approach to effectively encode distinguishable spectral signatures into the geometry of magnetic microstructures. Although based on different physical principles from those of optically probed nanoparticles, these geometrically defined magnetic microstructures permit a multiplexing functionality in the magnetic resonance radio-frequency spectrum that is in many ways analogous to that permitted by quantum dots in the optical spectrum. Additionally, in situ modification of particle geometries may facilitate radio-frequency probing of various local physiological variables.

Iron oxide particles are becoming an important contrast agent for magnetic resonance imaging (MRI) cell tracking studies. Simultaneous delivery of fluorescence indicators with the particles to individual cells offers the possibility of correlating optical images and MRI. In this work, it is demonstrated that micron-sized iron oxide particles (MPIOs) can be used as a carrier to deliver fluorescent probes to cells in culture as well as to migrating neural progenitors in vivo. Migrating progenitors were tracked with MRI and easily identified by histology because of the fluorescent probe. These data suggest that using MPIOs to deliver fluorescent probes should make it possible to combine MRI and optical imaging for in vivo cell tracking.

We demonstrate a direct resonant interaction between the mechanical motion of a mesoscopic resonator and the spin degrees of freedom of a sample of neutral atoms in the gas phase. This coupling, mediated by a magnetic particle attached to the tip of the miniature mechanical resonator, excites a coherent precession of the atomic spins about a static magnetic field. The novel coupled atom-resonator system may enable development of low-power, high-performance sensors, and enhance research efforts connected with the manipulation of cold atoms, quantum control, and high-resolution microscopy.

Background: The large amount of data that are currently produced in the biological sciences can no longer be explored and visualized efficiently with traditional, specialized software. Instead, new capabilities are needed that offer flexibility, rapid application development and deployment as standalone applications or available through the Web., Results: We describe a new software toolkit--the Molecular Biology Toolkit (MBT; http://mbt.sdsc.edu)--that enables fast development of applications for protein analysis and visualization. The toolkit is written in Java, thus offering platform-independence and Internet delivery capabilities. Several applications of the toolkit are introduced to illustrate the functionality that can be achieved., Conclusions: The MBT provides a well-organized assortment of core classes that provide a uniform data model for the description of biological structures and automate most common tasks associated with the development of applications in the molecular sciences (data loading, derivation of typical structural information, visualization of sequence and standard structural entities).