Relativistic Proton Production During the 14 July 2000 Solar Event: The Case for Multiple Source Mechanisms

Protons accelerated to relativistic energies by transient solar and interplanetary phenomena caused a ground-level cosmic ray enhancement on 14 July 2000, Bastille Day. Near-Earth spacecraft measured the proton flux directly and ground-based observatories measured the secondary responses to higher energy protons. We have modelled the arrival of these relativistic protons at Earth using a technique which deduces the spectrum, arrival direction and anisotropy of the high-energy protons that produce increased responses in neutron monitors. To investigate the acceleration processes involved we have employed theoretical shock and stochastic acceleration spectral forms in our fits to spacecraft and neutron monitor data. During the rising phase of the event (10:45 UT and 10:50 UT) we find that the spectrum between 140 MeV and 4 GeV is best fitted by a shock acceleration spectrum. In contrast, the spectrum at the peak (10:55 UT and 11:00 UT) and in the declining phase (11:40 UT) is best fitted with a stochastic acceleration spectrum. We propose that at least two acceleration processes were responsible for the production of relativistic protons during the Bastille Day solar event: (1) protons were accelerated to relativistic energies by a shock, presumably a coronal mass ejection (CME). (2) protons were also accelerated to relativistic energies by stochastic processes initiated by magnetohydrodynamic (MHD) turbulence.Comment: 38 pages, 9 figures, accepted for publication in the Astrophysical Journal, January, 200

The Case for a Low Extragalactic Gamma-ray Background

Measurements of the diffuse extragalactic gamma-ray background (EGRB) are complicated by a strong Galactic foreground. Estimates of the EGRB flux and spectrum, obtained by modeling the Galactic emission, have produced a variety of (sometimes conflicting) results. The latest analysis of the EGRET data found an isotropic flux I_x=1.45+-0.05 above 100 MeV, in units of 10^-5 s^-1 cm^-2 sr^-1. We analyze the EGRET data in search for robust constraints on the EGRB flux, finding the gamma-ray sky strongly dominated by Galactic foreground even at high latitudes, with no conclusive evidence for an additional isotropic component. The gamma-ray intensity measured towards the Galactic poles is similar to or lower than previous estimates of I_x. The high latitude profile of the gamma-ray data is disk-like for 40<|b[deg]|<70, and even steeper for |b|>70; overall it exhibits strong Galactic features and is well fit by a simple Galactic model. Based on the |b|>40 data we find that I_x<0.5 at a 99% confidence level, with evidence for a much lower flux. We show that correlations with Galactic tracers, previously used to identify the Galactic foreground and estimate I_x, are not satisfactory; the results depend on the tracers used and on the part of the sky examined, because the Galactic emission is not linear in the Galactic tracers and exhibits spectral variations across the sky. The low EGRB flux favored by our analysis places stringent limits on extragalactic scenarios involving gamma-ray emission, such as radiation from blazars, intergalactic shocks and production of ultra-high energy cosmic rays and neutrinos. We suggest methods by which future gamma-ray missions such as GLAST and AGILE could indirectly identify the EGRB.Comment: Accepted for publication in JCAP. Increased sizes of polar regions examined, and added discussion of spectral data. Results unchange

Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains

The respiratory syncytial virus (RSV) group A variant with the 72-nucleotide duplication in the G gene, genotype ON1, was first detected in Kilifi in 2012 and has almost completely replaced previously circulating genotype GA2 strains. This replacement suggests some fitness advantage of ON1 over the GA2 viruses, and might be accompanied by important genomic substitutions in ON1 viruses. Close observation of such a new virus introduction over time provides an opportunity to better understand the transmission and evolutionary dynamics of the pathogen. We have generated and analyzed 184 RSV-A whole genome sequences (WGS) from Kilifi (Kenya) collected between 2011 and 2016, the first ON1 genomes from Africa and the largest collection globally from a single location. Phylogenetic analysis indicates that RSV-A transmission into this coastal Kenya location is characterized by multiple introductions of viral lineages from diverse origins but with varied success in local transmission. We identify signature amino acid substitutions between ON1 and GA2 viruses within genes encoding the surface proteins (G, F), polymerase (L) and matrix M2-1 proteins, some of which were identified as positively selected, and thereby provide an enhanced picture of RSV-A diversity. Furthermore, five of the eleven RSV open reading frames (ORF) (i.e. G, F, L, N and P), analyzed separately, formed distinct phylogenetic clusters for the two genotypes. This might suggest that coding regions outside of the most frequently studied G ORF play a role in the adaptation of RSV to host populations with the alternative possibility that some of the substitutions are nothing more than genetic hitchhikers. Our analysis provides insight into the epidemiological processes that define RSV spread, highlights the genetic substitutions that characterize emerging strains, and demonstrates the utility of large-scale WGS in molecular epidemiological studies

Strength of Coronal Mass Ejection-Driven Shocks Near the Sun, and Its Importance in Predicting Solar Energetic Particle Events

Coronal shocks are important structures, but there are no direct observations of them in solar and space physics. The strength of shocks plays a key role in shock-related phenomena, such as radio bursts and solar energetic particle (SEP) generation. This paper presents an improved method of calculating Alfven speed and shock strength near the Sun. This method is based on using as many observations as possible, rather than one-dimensional global models. Two events, a relatively slow CME on 2001 September 15 and a very fast CME on 2000 June 15, are selected to illustrate the calculation process. The calculation results suggest that the slow CME drove a strong shock, with Mach number of 3.43 - 4.18, while the fast CME drove a relatively weak shock, with Mach number of 1.90 - 3.21. This is consistent with the radio observations, which find a stronger and longer decameter-hectometric (DH) type II radio burst during the first event, and a short DH type II radio burst during the second event. In particular, the alculation results explain the observational fact that the slow CME produced a major solar energetic particle (SEP) event, while the fast CME did not. Through a comparison of the two events, the importance of shock strength in predicting SEP events is addressed

Regulating for Responsibility: Reputation and Social Media

The framework brought forward by the United Kingdom's Defamation Act 2013 underlines a traditional hierarchy of expression in which news media are viewed as high-level speech. Although of a different form, social media are a dominant means of expression. The current study explores the rationale for a more robust and forceful discussion of responsibility in speech on social media platforms. The underlying premise here is that speech should be viewed as a qualified good and that a more appropriate paradigm is one found in the phrase ‘freedom to participate’

Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates

Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (trans,trans)-farnesyl diphosphate (FPP) (1a) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (cis,trans)-FPP (1b) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (cis,trans)-FPP (1b) to exclusively (≥99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-trans FPP (1a) and (cis,trans)-FPP (1b) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

Background: Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods: In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results: From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion: We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community

Development of an intervention to improve appropriate polypharmacy in older people in primary care using a theory-based method

BACKGROUND: It is advocated that interventions to improve clinical practice should be developed using a systematic approach and intervention development methods should be reported. However, previous interventions aimed at ensuring that older people receive appropriate polypharmacy have lacked details on their development. This study formed part of a multiphase research project which aimed to develop an intervention to improve appropriate polypharmacy in older people in primary care. METHODS: The target behaviours for the intervention were prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists. Intervention development followed a systematic approach, including previous mapping of behaviour change techniques (BCTs) to key domains from the Theoretical Domains Framework that were perceived by GPs and pharmacists to influence the target behaviours. Draft interventions were developed to operationalise selected BCTs through team discussion. Selection of an intervention for feasibility testing was guided by a subset of the APEASE (Affordability, Practicability, Effectiveness/cost-effectiveness, Acceptability, Side-effects/safety, Equity) criteria. RESULTS: Three draft interventions comprising selected BCTs were developed, targeting patients, pharmacists and GPs, respectively. Following assessment of each intervention using a subset of the APEASE criteria (affordability, practicability, acceptability), the GP-targeted intervention was selected for feasibility testing. This intervention will involve a demonstration of the behaviour and will be delivered as an online video. The video demonstrating how GPs can prescribe appropriate polypharmacy during a typical consultation with an older patient will also demonstrate salience of consequences (feedback emphasising the positive outcomes of performing the behaviour). Action plans and prompts/cues will be used as complementary intervention components. The intervention is designed to facilitate the prescribing of appropriate polypharmacy in routine practice. CONCLUSION: A GP-targeted intervention to improve appropriate polypharmacy in older people has been developed using a systematic approach. Intervention content has been specified using an established taxonomy of BCTs and selected to maximise feasibility. The results of a future feasibility study will help to determine if the theory-based intervention requires further refinement before progressing to a larger scale randomised evaluation

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies