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

Always Better Control-Vital Essential Desirable analysis of the drugs used in health centres of Ahmedabad district

Background: The basic principle of inventory control is Always Better Control (ABC) based on cost criteria and Vital Essential Desirable (VED) on criticality. Inequity in drug prioritization and expenses directly affects the health of the community. Study design: Based on ABC-VED matrix, inventory analysis was done. Study area: Community health centre (CHC) - Singarva, two primary health centres (PHC) - Kanbha and Sanathal and two urban health centre (UHC) - Amraiwadi and Sabarmati. Study period: December 2012 to December 2013.Methods: The drugs were first categorized by ABC method and then by VED method. On coupling the two techniques, ABC-VED matrix was made and drugs were classified in to Category I (AV + BV +CV + AE + AD), Category II (BE + CE + BD) and Category III (CD).Results: According to VED analysis large amount of money was spent on D category that is; 35% of annual drug expenditure (ADE) from CHC, 7.6% and 23.4% from both the PHC respectively, 20.1% and 24.7% from both the UHCs. On considering the ABC-VED matrix analysis the ADE spent on Class III was 6.6% among CHC, 1.2% and 1.5% among PHC, 2.6% and 7.2% among the UHC.Conclusion: The ADE used among the ABC-VED Class III should be avoided and the ADE on Class II drugs should be controlled and used judiciously

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

Influence of molecular imaging on patient selection for treatment intensification prior to salvage radiation therapy for prostate cancer: a post hoc analysis of the PROPS trial

Background: The impact of molecular imaging (MI) on patient management after biochemical recurrence (BCR) following radical prostatectomy has been described in many studies. However, it is not known if MI-induced management changes are appropriate. This study aimed to determine if androgen deprivation therapy (ADT) management plan is improved by MI in patients who are candidates for salvage radiation therapy. / Methods: Data were analyzed from the multicenter prospective PROPS trial evaluating PSMA/Choline PET in patients being considered for salvage radiotherapy (sRT) with BCR after prostatectomy. We compared the pre- and post-MI ADT management plans for each patient and cancer outcomes as predicted by the MSKCC nomogram. A higher percentage of predicted BCR associated with ADT treatment intensification after MI was considered as an improvement in a patient’s management. / Results: Seventy-three patients with a median PSA of 0.38 ng/mL were included. In bivariate analysis, a positive finding on MI (local or metastatic) was associated with decision to use ADT with an odds ratio of 3.67 (95% CI, 1.25 to 10.71; p = 0.02). No factor included in the nomogram was associated with decision to use ADT. Also, MI improved selection of patients to receive ADT based on predicted BCR after sRT : the predicted nomogram 5-year biochemical-free survivals were 52.5% and 43.3%, (mean difference, 9.2%; 95% CI 0.8 to 17.6; p = 0.03) for sRT alone and ADT±sRT subgroups, while there was no statistically significant difference between subgroups before MI. / Conclusions: PSMA and/or Choline PET/CT before sRT can potentially improve patient ADT management by directing clinicians towards more appropriate intensification

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

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

Chemoproteomics reveals Toll-like receptor fatty acylation

Partial funding for Open Access provided by The Ohio State University Open Access Fund.Background: Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells. Results: A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands. Conclusions: This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. Spalmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity.This work was supported by funding from the NIH/NIAID (grant R00AI095348 to J.S.Y.), the NIH/NIGMS (R01GM087544 to HCH), and the Ohio State University Public Health Preparedness for Infectious Diseases (PHPID) program. NMC is supported by the Ohio State University Systems and Integrative Biology Training Program (NIH/NIGMS grant T32GM068412). BWZ is a fellow of the National Science Foundation Graduate Research Fellowship Program (DGE-0937362)