Planar charged-particle trajectories in multipole magnetic fields

International audienceThis paper provides a complete generalization of the classic result that the radius of curvature (?) of a charged-particle trajectory confined to the equatorial plane of a magnetic dipole is directly proportional to the cube of the particle's equatorial distance (?) from the dipole (i.e. ? ? ?3). Comparable results are derived for the radii of curvature of all possible planar charged-particle trajectories in an individual static magnetic multipole of arbitrary order m and degree n. Such trajectories arise wherever there exists a plane (or planes) such that the multipole magnetic field is locally perpendicular to this plane (or planes), everywhere apart from possibly at a set of magnetic neutral lines. Therefore planar trajectories exist in the equatorial plane of an axisymmetric (m = 0), or zonal, magnetic multipole, provided n is odd: the radius of curvature varies directly as ?n+2. This result reduces to the classic one in the case of a zonal magnetic dipole (n =1). Planar trajectories exist in 2m meridional planes in the case of the general tesseral (0 m n) magnetic multipole. These meridional planes are defined by the 2m roots of the equation cos[m(? ? ?nm)] = 0, where ?nm = (1/m) arctan (hnm/gnm); gnm and hnm denote the spherical harmonic coefficients. Equatorial planar trajectories also exist if (n ? m) is odd. The polar axis (? = 0,?) of a tesseral magnetic multipole is a magnetic neutral line if m > 1. A further 2m(n ? m) neutral lines exist at the intersections of the 2m meridional planes with the (n ? m) cones defined by the (n ? m) roots of the equation Pnm(cos ?) = 0 in the range 0 ? ?, where Pnm(cos ?) denotes the associated Legendre function. If (n ? m) is odd, one of these cones coincides with the equator and the magnetic field is then perpendicular to the equator everywhere apart from the 2m equatorial neutral lines. The radius of curvature of an equatorial trajectory is directly proportional to ?n+2 and inversely proportional to cos[m(? ? ?nm)]. Since this last expression vanishes at the 2m equatorial neutral lines, the radius of curvature becomes infinitely large as the particle approaches any one of these neutral lines. The radius of curvature of a meridional trajectory is directly proportional to rn+2, where r denotes radial distance from the multipole, and inversely proportional to Pnm(cos ?)/sin θ. Hence the radius of curvature becomes infinitely large if the particle approaches the polar magnetic neutral line (m > 1) or any one of the 2m(n ? m) neutral lines located at the intersections of the 2m meridional planes with the (n ? m) cones. Illustrative particle trajectories, derived by stepwise numerical integration of the exact equations of particle motion, are presented for low-degree (n ? 3) magnetic multipoles. These computed particle trajectories clearly demonstrate the "non-adiabatic'' scattering of charged particles at magnetic neutral lines. Brief comments are made on the different regions of phase space defined by regular and irregular trajectories

Variability of dayside convection and motions of the cusp/cleft aurora

We present measurements of the ionospheric plasma flow over the range of invariant latitudes 71–76°, observed at 10-second resolution using both the EISCAT radars, with simultaneous observations of the 630 nm cusp/cleft aurora made by a meridian-scanning photometer at Ny Ålesund, Svalbard. A major increase in the trans-auroral voltage from 5 to 40 kV (associated with sunward convection in the early afternoon sector) is found to follow a southward motion of the aurora and coincide with the onset of regular transient auroral breakup events. It is shown that these observations are consistent with recent theoretical work on how ionospheric flows are excited by time-dependent reconnection at the dayside magnetopause

A retrieval analysis of the Precice intramedullary limb lengthening system

OBJECTIVES: The Precice nail is the latest intramedullary lengthening nail with excellent early outcomes. Implant complications have led to modification of the nail design. The aim of this study was to perform a retrieval study of Precice nails following lower-limb lengthening and to assess macroscopical and microscopical changes to the implants and evaluate differences following design modification, with the aim of identifying potential surgical, implant, and patient risk factors. METHODS: A total of 15 nails were retrieved from 13 patients following lower-limb lengthening. Macroscopical and microscopical surface damage to the nails were identified. Further analysis included radiology and micro-CT prior to sectioning. The internal mechanism was then analyzed with scanning electron microscopy and energy dispersive x-ray spectroscopy to identify corrosion. RESULTS: Seven male and three female patients underwent 12 femoral lengthenings. Three female patients underwent tibial lengthening. All patients obtained the desired length with no implant failure. Surface degradation was noted on the telescopic part of every nail design, less on the latest implants. Microscopical analysis confirmed fretting and pitting corrosion. Following sectioning, black debris was noted in all implants. The early designs were found to have fractured actuator pins and the pin and bearings showed evidence of corrosive debris. The latest designs showed evidence of biological deposits suggestive of fluid ingress within the nail but no corrosion. CONCLUSION: This study confirms less internal corrosion following modification, but evidence of titanium debris remains. We recommend no change to current clinical practice. However, potential reuse of the Precice nail, for secondary limb lengthening in the same patient, should be undertaken with caution

HDL-Associated Estradiol Stimulates Endothelial NO Synthase and Vasodilation in an SR-BI–Dependent Manner

Cardiovascular diseases remain the leading cause of death in the United States. Two factors associated with a decreased risk of developing cardiovascular disease are elevated HDL levels and sex — specifically, a decreased risk is found in premenopausal women. HDL and estrogen stimulate eNOS and the production of nitric oxide, which has numerous protective effects in the vascular system including vasodilation, antiadhesion, and anti-inflammatory effects. We tested the hypothesis that HDL binds to its receptor, scavenger receptor class B type I (SR-BI), and delivers estrogen to eNOS, thereby stimulating the enzyme. HDL isolated from women stimulated eNOS, whereas HDL isolated from men had minimal activity. Studies with ovariectomized and ovariectomized/estrogen replacement mouse models demonstrated that HDL-associated estradiol stimulation of eNOS is SR-BI dependent. Furthermore, female HDL, but not male HDL, promoted the relaxation of muscle strips isolated from C57BL/6 mice but not SR-BI null mice. Finally, HDL isolated from premenopausal women or postmenopausal women receiving estradiol replacement therapy stimulated eNOS, whereas HDL isolated from postmenopausal women did not stimulate eNOS. We conclude that HDL-associated estrodial is capable of the stimulating eNOS. These studies establish a new paradigm for examining the cardiovascular effects of HDL and estrogen

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer.

BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816

Moving from advocacy to activism? The fourth WHO global forum on human resources for health and implications for dentistry

As we debate shaping the future oral health workforce within the UK, to meet the needs of current and future populations, it is helpful to take an international perspective on this very important issue. Globally, there is a strong recognition that human resources for health (HRH) are fundamentally important to deliver effective care, accessible to all people. This paper reviews the outcome of the fourth global forum held by the World Health Organisation (WHO) in Dublin which highlighted the urgency for action. The main objectives of the forum were to advance the implementation of (i) the WHO Global Strategy on HRH 2030 and (ii) the United Nations High-Level Commission's Health Employment and Economic Growth recommendations. From an oral health perspective, the global burden of oral disease remains huge with untreated dental caries, periodontal disease and tooth loss ranking among the most prevalent conditions worldwide. Major considerations are how dental education, practice delivery and/or oral health systems as a whole could and should innovate to accommodate the growing needs of the population. As dental professionals, it also becomes necessary for us to engage and play a proactive role in this change process. Due to growing differences between population needs and available services, it is necessary for oral health personnel to work more closely with the broader health workforce so as to identify solutions that are in the best interests of the patients and populations at large.M. Balasubramanian, L. Davda, S. D. Short, and J. E. Gallaghe

A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ε-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere®in the MCF-7 TAX30 cell culture, but the differences were not significant (p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere®(p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer

Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy

<p>Abstract</p> <p>Background</p> <p>Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.</p> <p>Methods</p> <p>To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) <it>in vitro</it>.</p> <p>Results</p> <p>We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.</p> <p>Conclusion</p> <p>Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.</p