Validation of the theoretical domains framework for use in behaviour change and implementation research

BACKGROUND: An integrative theoretical framework, developed for cross-disciplinary implementation and other behaviour change research, has been applied across a wide range of clinical situations. This study tests the validity of this framework. METHODS: Validity was investigated by behavioural experts sorting 112 unique theoretical constructs using closed and open sort tasks. The extent of replication was tested by Discriminant Content Validation and Fuzzy Cluster Analysis. RESULTS: There was good support for a refinement of the framework comprising 14 domains of theoretical constructs (average silhouette value 0.29): 'Knowledge', 'Skills', 'Social/Professional Role and Identity', 'Beliefs about Capabilities', 'Optimism', 'Beliefs about Consequences', 'Reinforcement', 'Intentions', 'Goals', 'Memory, Attention and Decision Processes', 'Environmental Context and Resources', 'Social Influences', 'Emotions', and 'Behavioural Regulation'. CONCLUSIONS: The refined Theoretical Domains Framework has a strengthened empirical base and provides a method for theoretically assessing implementation problems, as well as professional and other health-related behaviours as a basis for intervention development

Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya

Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear. Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori. Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21–24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections. Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear

Kinetics of the neutralizing antibody response to respiratory syncytial virus infections in a birth cohort

The kinetics of respiratory syncytial virus (RSV) neutralizing antibodies following birth, primary and secondary infections are poorly defined. The aims of the study were to measure and compare neutralizing antibody responses at different time points in a birth cohort followed-up over three RSV epidemics. Rural Kenyan children, recruited at birth between 2002 and 2003, were monitored for RSV infection over three epidemic seasons. Cord and 3-monthly sera, and acute and convalescent sera following RSV infection, were assayed in 28 children by plaque reduction neutralization test (PRNT). Relative to the neutralizing antibody titers of pre-exposure control sera (1.8 log10 PRNT), antibody titers following primary infection were (i) no different in sera collected between 0 and 0.4 months post-infection (1.9 log10 PRNT, P = 0.146), (ii) higher in sera collected between 0.5 and 0.9 (2.8 log10 PRNT, P < 0.0001), 1.0–1.9 (2.5 log10 PRNT, P < 0.0001), and 2.0–2.9 (2.3 log10 PRNT, P < 0.001) months post-infection, and (iii) no different in sera collected at between 3.0 and 3.9 months post-infection (2.0 log10 PRNT, P = 0.052). The early serum neutralizing response to secondary infection (3.02 log10 PRNT) was significantly greater than the early primary response (1.9 log10 PRNT, P < 0.0001). Variation in population-level virus transmission corresponded with changes in the mean cohort-level neutralizing titers. It is concluded that following primary RSV infection the neutralizing antibody response declines to pre-infection levels rapidly (∼3 months) which may facilitate repeat infection. The kinetics of the aggregate levels of acquired antibody reflect seasonal RSV occurrence, age, and infection history

Incidence and severity of respiratory syncytial virus pneumonia in rural Kenyan children identified through hospital surveillance

Background.Although necessary for developing a rationale for vaccination, the burden of severe respiratory syncytial virus (RSV) disease in children in resource‐poor settings remains poorly defined. Methods.We conducted prospective surveillance of severe and very severe pneumonia in children aged <5 years admitted from 2002 through 2007 to Kilifi district hospital in coastal Kenya. Nasal specimens were screened for RSV antigen by immunofluorescence. Incidence rates were estimated for the well‐defined population. Results.Of 25,149 hospital admissions, 7359 patients (29%) had severe or very severe pneumonia, of whom 6026 (82%) were enrolled. RSV prevalence was 15% (20% among infants) and 27% during epidemics (32% among infants). The proportion of case patients aged 3 months was 65%, and the proportion aged 6 months was 43%. Average annual hospitalization rates were 293 hospitalizations per 100,000 children aged <5 years (95% confidence interval, 271–371 hospitalizations per 100,000 children aged <5 years) and 1107 hospitalizations per 100,000 infants (95% confidence interval, 1012–1211 hospitalizations per 100,000 infants). Hospital admission rates were double in the region close to the hospital. Few patients with RSV infection had life‐threatening clinical features or concurrent serious illnesses, and the associated mortality was 2.2%. Conclusions.In this low‐income setting, rates of hospital admission with RSV‐associated pneumonia are substantial; they are comparable to estimates from the United States but considerably underestimate the burden in the full community. An effective vaccine for children aged >2 months (outside the age group of poor responders) could prevent a large portion of RSV disease. Severity data suggest that the justification for RSV vaccination will be based on the prevention of morbidity, not mortality

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

On the Brightness and Waiting-time Distributions of a Type III Radio Storm observed by STEREO/WAVES

Type III solar radio storms, observed at frequencies below approximately 16 MHz by space borne radio experiments, correspond to the quasi-continuous, bursty emission of electron beams onto open field lines above active regions. The mechanisms by which a storm can persist in some cases for more than a solar rotation whilst exhibiting considerable radio activity are poorly understood. To address this issue, the statistical properties of a type III storm observed by the STEREO/WAVES radio experiment are presented, examining both the brightness distribution and (for the first time) the waiting-time distribution. Single power law behavior is observed in the number distribution as a function of brightness; the power law index is approximately 2.1 and is largely independent of frequency. The waiting-time distribution is found to be consistent with a piecewise-constant Poisson process. This indicates that during the storm individual type III bursts occur independently and suggests that the storm dynamics are consistent with avalanche type behavior in the underlying active region.Comment: 14 pages, 4 figures, 1 table. Accepted for publication in Astrophysical Journal Letter

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

A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism

We present 109 near full-length HIV genomes amplified from blood serum samples obtained during early 1986 from across Uganda, which to our knowledge is the earliest and largest population sample from the initial phase of the HIV epidemic in Africa. Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller 'intermediate' genome dataset from 1998 to 1999 and a 'modern' genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73/109), to 57% (26/46) to 17% (82/465) respectively (p < 0.0001). Subtype D has previously been shown to have a faster rate of disease progression than other subtypes in East African population studies, and to have a higher propensity to use the CXCR4 co-receptor ("X4 tropism"); associated with a decrease in time to AIDS. Here we find significant differences in predicted tropism between A1 and D subtypes in all three sample periods considered, which is particularly striking the 1986 sample: 66% (53/80) of subtype D env sequences were predicted to be X4 tropic compared with none of the 24 subtype A1. We also analysed the frequency of subtype in the envelope region of inter-subtype recombinants, and found that subtype A1 is over-represented in env, suggesting recombination and selection have acted to remove subtype D env from circulation. The reduction of subtype D frequency over three decades therefore appears to be a result of selective pressure against X4 tropism and its higher virulence. Lastly, we find a subtype D specific codon deletion at position 24 of the V3 loop, which may explain the higher propensity for subtype D to utilise X4 tropism