Challenges and recommendations for magnetic hyperthermia characterization measurements

PURPOSE: The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields - a process known as magnetic field hyperthermia (MFH) - can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating - characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg - is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. MATERIALS AND METHODS: An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing. RESULTS: The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. CONCLUSION: We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology

Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly over-expressed in mycosis fungoides and correlates with poor prognosis

Mycosis fungoides (MF) often mimics the common chronic inflammatory skin diseases and is difficult to be diagnosed with certainty, partly because of the lack of well-characterized molecular markers. Previously, we discovered that TOX, a key T cell development regulator,was aberrantly over-expressed in early stage MF. In the current multi-center study involving two independent patient cohorts, we determined the prevalence of TOX over-expression in the full spectrum of MF skin biopsies, and tested if TOX expression levels correlated with long term clinical outcomes. We examined TOX expression levels in 113 MF biopsies. We found that the MF biopsies expressed higher TOX mRNA than the controls in both cohorts (17.9 fold in cohort 1, P = 0.002; 5.8 fold in cohort 2, P < 0.0001). In addition, thicker skin lesions such as plaques and tumors expressed even higher TOX levels than thinner patches. Further, TOX over-expression differentiated MF from the controls (area under the curve [AUC]=0.87, P < 0.0001). Finally, high TOX mRNA levels correlated with increased risks of disease progression (P = 0.003) and disease-specific mortality (P = 0.008). In conclusion, TOX may be a useful marker for improving MF diagnosis and prognostication

Measurement of Spin Transfer Observables in Antiproton-Proton -> Antilambda-Lambda at 1.637 GeV/c

Spin transfer observables for the strangeness-production reaction Antiproton-Proton -> Antilambda-Lambda have been measured by the PS185 collaboration using a transversely-polarized frozen-spin target with an antiproton beam momentum of 1.637 GeV/c at the Low Energy Antiproton Ring at CERN. This measurement investigates observables for which current models of the reaction near threshold make significantly differing predictions. Those models are in good agreement with existing measurements performed with unpolarized particles in the initial state. Theoretical attention has focused on the fact that these models produce conflicting predictions for the spin-transfer observables D_{nn} and K_{nn}, which are measurable only with polarized target or beam. Results presented here for D_{nn} and K_{nn} are found to be in disagreement with predictions from existing models. These results also underscore the importance of singlet-state production at backward angles, while current models predict complete or near-complete triplet-state dominance.Comment: 5 pages, 3 figure

Measurement of the Eta Production in Proton Proton Collisions with the COSY Time of Flight Spectrometer

The reaction pp -> pp eta was measured at excess energies of 15 and 41 MeV at an external target of the Juelich Cooler Synchrotron COSY with the Time of Flight Spectrometer. About 25000 events were measured for the excess energy of 15 MeV and about 8000 for 41 MeV. Both protons of the process pp eta were detected with an acceptance of nearly 100% and the eta was reconstructed by the missing mass technique. For both excess energies the angular distributions are found to be nearly isotropic. In the invariant mass distributions strong deviations from the pure phase space distributions are seen.Comment: 15 pages, 14 figures, 4 table

Production of ω\omega mesons in proton-proton collisions

The cross section for the production of $\omega$ mesons in proton-proton collisions has been measured in a previously unexplored region of incident energies. Cross sections were extracted at 92 MeV and 173 MeV excess energy, respectively. The angular distribution of the $\omega$ at $\epsilon$=173 MeV is strongly anisotropic, demonstrating the importance of partial waves beyond pure s-wave production at this energy.Comment: 12 pages, 4 figures submitted to Physics Letters B v2: figure 1 added, discussion detailing the data analysis, figure 3 (fig. 2 in v1) modified in line styles and systematic errors displayed on dat

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (&#8804;100 kg/&#62;100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with &#60;5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was &#8805;20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and &#8805;75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p&#60;0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p&#60;0.001), ACR50 (p&#8804;0.05) and PASI75 (p&#60;0.001); all benefits were sustained through week 52. Among patients previously treated with &#8805;1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Photoproduction of Neutral Pions off Protons

Photoproduction of neutral pions has been studied with the CBELSA/TAPS detector in the reaction $\gamma p\to p\pi^0$ for photon energies between 0.85 and 2.50 GeV. The $\pi^0$ mesons are observed in their dominant neutral decay mode: $\pi^0\to\gamma\gamma$. For the first time, the differential cross sections cover the very forward region, $\theta_{\rm c.m.}<60^\circ$. A partial-wave analysis of these data within the Bonn-Gatchina framework observes the high-mass resonances $G_{17}$(2190), $D_{13}$(2080), and $D_{15}$(2070).Comment: 12 pages, 9 figures, minor modifications to PWA sectio

Experimental determination of the complete spin structure for anti-proton + proton -> anti-\Lambda + \Lambda at anti-proton beam momentum of 1.637 GeV/c

The reaction anti-proton + proton -> anti-\Lambda + \Lambda -> anti-proton + \pi^+ + proton + \pi^- has been measured with high statistics at anti-proton beam momentum of 1.637 GeV/c. The use of a transversely-polarized frozen-spin target combined with the self-analyzing property of \Lambda/anti-\Lambda decay allows access to unprecedented information on the spin structure of the interaction. The most general spin-scattering matrix can be written in terms of eleven real parameters for each bin of scattering angle, each of these parameters is determined with reasonable precision. From these results all conceivable spin-correlations are determined with inherent self-consistency. Good agreement is found with the few previously existing measurements of spin observables in anti-proton + proton -> anti-\Lambda + \Lambda near this energy. Existing theoretical models do not give good predictions for those spin-observables that had not been previously measured.Comment: To be published in Phys. Rev. C. Tables of results (i.e. Ref. 24) are available at http://www-meg.phys.cmu.edu/~bquinn/ps185_pub/results.tab 24 pages, 16 figure

Photoproduction of meson pairs: First measurement of the polarization observable I^s

The polarization observable I^s, a feature exclusive to the acoplanar kinematics of multi-meson final states produced via linearly polarized photons, has been measured for the first time. Results for the reaction g p -> p pi0 eta are presented for incoming photon energies between 970 MeV and 1650 MeV along with the beam asymmetry I^c. The comparably large asymmetries demonstrate a high sensitivity of I^s to the dynamics of the reaction. Fits using Bonn-Gatchina partial wave analysis demonstrate that the new polarization observables carry significant information on the contributing partial waves.Comment: 11 pages, 6 figures, v2 to appear in Phys. Lett.