Towards Comparison of Ultrasound Dose Measurements - Current Capabilities and Open Challenges

open7sìThe aim of this work is to evaluate measurement methods for dosimetry and exposimetry quantities that were developed in the EMRP project “Dosimetry for Ultrasound Therapy -DUTy” by comparing the measurement results for three common quantities from three national laboratories. It further aims to investigate the general feasibility of possible future (key) comparisons for dosimetry and exposimetry quantities and to identify possible open challenges towards this goal. The general format is similar to a metrological comparison, with which the National Metrological Institutes, NMIs, are already familiar. The first step involved the agreement of the protocol that was to specify the set of transducers to be circulated and the measurement conditions. Two transducers were circulated and different drive voltage levels and pulsing regimes were defined and tissue mimicking materials (TMMs) characteristics were specified. Each lab was asked to prepare the TMMs for their own measurements with the inclusion of formulations and preparation instructions specified in the protocol. Uncertainties of the input data were to be declared by the participating laboratories.openDurando, G.; Guglielmone, C.; Haller, J.; Georg, O.; Shaw, A.; Martin, E.; Karaböce, B.Durando, Giovanni; Guglielmone, CLAUDIO LUIGI DOME; Haller, J.; Georg, O.; Shaw, A.; Martin, E.; Karaböce, B

Pharmacokinetic study on pradofloxacin in the dog – Comparison of serum analysis, ultrafiltration and tissue sampling after oral administration

Background: Pradofloxacin, a newly developed 8-cyano-fluoroquinolone, show enhanced activity against Grampositive organisms and anaerobes to treat canine and feline bacterial infections. The purpose of this cross-over study was to measure the unbound drug concentration of pradofloxacin in the interstitial fluid (ISF) using ultrafiltration and to compare the kinetics of pradofloxacin in serum, ISF and tissue using enrofloxacin as reference. Results: After oral administration of enrofloxacin (5 mg/kg) and pradofloxacin (3 mg/kg and 6 mg/kg, respectively), serum collection and ultrafiltration in regular intervals over a period of 24 h were performed, followed by tissue sampling at the end of the third dosing protocol (pradofloxacin 6 mg/kg). Peak concentrations of pradofloxacin (3 mg/kg) were 1.55±0.31 μg/ml in the ISF and 1.85±0.23 μg/ml in serum and for pradofloxacin (6 mg/kg) 2.71±0.81 μg/kg in the ISF and 2.77±0.64 μg/kg in serum; both without a statistical difference between ISF and serum. Comparison between all sampling approaches showed no consistent pattern of statistical differences. Conclusions: Despite some technical shortcomings the ultrafiltration approach appears to be the most sensitive sampling technique to estimate pharmacokinetic values of pradofloxacin at the infection site. Pharmacokinetics – Pradofloxacin – Ultrafiltration – Dog – Oral Administration

Aims and structure of the German Research Consortium BipoLife for the study of bipolar disorder

Background: Bipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need. Structure: A research consortium of ten universities across Germany has therefore implemented a 4 year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics). Conclusions: This article aims to outline the rationale, design, and methods of these individual studies

Aims and structure of the German Research Consortium BipoLife for the study of bipolar disorder

Background: Bipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need. Structure: A research consortium of ten universities across Germany has therefore implemented a 4 year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics). Conclusions: This article aims to outline the rationale, design, and methods of these individual studies

Validation of a serum ELISA test for cyathostomin infection in equines

Cyathostomins are ubiquitous equine nematodes. Infection can result in larval cyathostominosis due to mass larval emergence. Although faecal egg count (FEC) tests provide estimates of egg shedding, these correlate poorly with burden and provide no information on mucosal/luminal larvae. Previous studies describe a serum IgG(T)-based ELISA (CT3) that exhibits utility for detection of mucosal/luminal cyathostomins. Here, this ELISA is optimised/validated for commercial application using sera from horses for which burden data were available. Optimisation included addition of total IgG-based calibrators to provide standard curves for quantification of antigen-specific IgG(T) used to generate a CT3-specific ‘serum score’ for each horse. Validation dataset results were then used to assess the optimised test’s performance and select serum score cut-off values for diagnosis of burdens above 1000, 5000 and 10,000 cyathostomins. The test demonstrated excellent performance (Receiver Operating Characteristic Area Under the Curve values >0.9) in diagnosing infection, with >90% sensitivity and >70% specificity at the selected serum score cut-off values. CT3-specific serum IgG(T) profiles in equines in different settings were assessed to provide information for commercial test use. These studies demonstrated maternal transfer of CT3-specific IgG(T) in colostrum to newborns, levels of which declined before increasing as foals consumed contaminated pasture. Studies in geographically distinct populations demonstrated that the proportion of horses that reported as test positive at a 14.37 CT3 serum score (1000-cyathostomin threshold) was associated with parasite transmission risk. Based on the results, inclusion criteria for commercial use were developed. Logistic regression models were developed to predict probabilities that burdens of individuals are above defined thresholds based on the reported serum score. The models performed at a similar level to the serum score cut-off approach. In conclusion, the CT3 test provides an option for veterinarians to obtain evidence of low cyathostomin burdens that do not require anthelmintic treatment and to support diagnosis of infection

Antibodies to the endoplasmic reticulum-resident chaperones calnexin, BiP and Grp94 in patients with rheumatoid arthritis and systemic lupus erythematosus

Objectives. To investigate the presence of autoantibodies against mammalian chaperones of the endoplasmic reticulum (ER) in patients with RA and other immune-mediated diseases. Methods. Sera from healthy donors, from early RA patients with two follow-up samples, patients with SLE, SSc and IBD were collected and analysed for anti-ER chaperone antibodies. Detection of serum IgG antibodies against immunoglobulin heavy chain binding protein (BiP), glucose-regulated protein 94 (Grp94) and calnexin was carried out using ELISA. The specificity of sera positive for individual ER chaperones was confirmed by immunoblotting. Statistical analysis was performed using Welch's t-test, Mann-Whitney U-test, partial correlation and Pearson's correlation. Results. In patients with RA and SLE, autoantibody titres against BiP, Grp94 and calnexin were significantly higher than those in healthy controls. These autoantibodies were detectable in patients with early RA and titres remained stable for at least 6-12 months. Also several SSc and IBD patients exhibited autoantibodies against these ER chaperones; however, titres and frequencies were lower than in RA or SLE patients. Furthermore, anti-calnexin antibodies correlated significantly with the presence of BiP and Grp94 autoantibodies in patients with RA and SLE. Conclusion. Calnexin and Grp94 were identified as novel autoantigens in RA and calnexin in SLE. Since calnexin, Grp94 and BiP are ER-resident proteins of eukaryotic cells, our data suggest that autoantibody generation against ER chaperones is independent of initial exposure to the corresponding bacterial chaperones; rather, ER chaperones may represent genuine autoantigen

Enhanced Vitreous Imaging in Healthy Eyes Using Swept Source Optical Coherence Tomography

Purpose To describe enhanced vitreous imaging for visualization of anatomic features and microstructures within the posterior vitreous and vitreoretinal interface in healthy eyes using swept-source optical coherence tomography (SS-OCT). The study hypothesis was that long-wavelength, high-speed, volumetric SS-OCT with software registration motion correction and vitreous window display or high-dynamic-range (HDR) display improves detection sensitivity of posterior vitreous and vitreoretinal features compared to standard OCT logarithmic scale display. Design Observational prospective cross-sectional study. Methods Multiple wide-field three-dimensional SS-OCT scans (500×500A-scans over 12×12 mm2) were obtained using a prototype instrument in 22 eyes of 22 healthy volunteers. A registration motion-correction algorithm was applied to compensate motion and generate a single volumetric dataset. Each volumetric dataset was displayed in three forms: (1) standard logarithmic scale display, enhanced vitreous imaging using (2) vitreous window display and (3) HDR display. Each dataset was reviewed independently by three readers to identify features of the posterior vitreous and vitreoretinal interface. Detection sensitivities for these features were measured for each display method. Results Features observed included the bursa premacularis (BPM), area of Martegiani, Cloquet's/BPM septum, Bergmeister papilla, posterior cortical vitreous (hyaloid) detachment, papillomacular hyaloid detachment, hyaloid attachment to retinal vessel(s), and granular opacities within vitreous cortex, Cloquet's canal, and BPM. The detection sensitivity for these features was 75.0% (95%CI: 67.8%–81.1%) using standard logarithmic scale display, 80.6% (95%CI: 73.8%–86.0%) using HDR display, and 91.9% (95%CI: 86.6%–95.2%) using vitreous window display. Conclusions SS-OCT provides non-invasive, volumetric and measurable in vivo visualization of the anatomic microstructural features of the posterior vitreous and vitreoretinal interface. The vitreous window display provides the highest sensitivity for posterior vitreous and vitreoretinal interface analysis when compared to HDR and standard OCT logarithmic scale display. Enhanced vitreous imaging with SS-OCT may help assess the natural history and treatment response in vitreoretinal interface diseases.Massachusetts Lions Eye Research Fund, Inc.Research to Prevent Blindness, Inc. (United States)United States. Air Force Office of Scientific Research (grant FA9550-1010551)United States. Air Force Office of Scientific Research (grant FA9550-12-1-0499)German Research Foundation (DFG-HO-1791/11-1)German Research Foundation (DFGGSC80-SAOT)German Research Foundation (DFG Research Training Group 1773)Champalimaud Foundation (Champalimaud Vision Award Fund)National Institutes of Health (U.S.) (R01- EY11289-28)National Institutes of Health (U.S.) (R01-CA075289-16)National Institutes of Health (U.S.) (R44-EY022864-01