Looking inside the black box : a theory-based process evaluation alongside a randomised controlled trial of printed educational materials (the Ontario printed educational message, OPEM) to improve referral and prescribing practices in primary care in Ontario, Canada

Background: Randomised controlled trials of implementation strategies tell us whether (or not) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change. Theory-based process evaluations collect data on theoretical constructs alongside randomised trials to explore possible causal mechanisms and effect modifiers. This is similar to measuring intermediate endpoints in clinical trials to further understand the biological basis of any observed effects (for example, measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths). This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message (OPEM) trial. We hypothesize that the OPEM interventions are most likely to operate through changes in physicians' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control. We will test this hypothesis using a well-validated social cognition model, the theory of planned behaviour (TPB) that incorporates these constructs. Methods/design: We will develop theory-based surveys using standard methods based upon the TPB for the second and third replications, and survey a subsample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed, the evidence based newsletter used for the interventions. In the third replication, our study will converge with the "TRY-ME" protocol (a second study conducted alongside the OPEM trial), in which the content of educational messages was constructed using both standard methods and methods informed by psychological theory. We will modify Dillman's total design method to maximise response rates. Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable (intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension). We will then compare groups using methods appropriate for comparing independent samples to determine whether there have been changes in the predicted constructs (attitudes, subjective norms, or intentions) across the study groups as hypothesised, and will assess the convergence between the process evaluation results and the main trial results.The OPEM trial and OPEM process evaluation are funded by the Canadian Institute of Health Research (CIHR). The OPEM process evaluation study was developed as part of the CIHR funded interdisciplinary capacity enhancement team KT-ICEBeRG. Gaston Godin, Jeremy Grimshaw and France Légaré hold Canada Research Chairs. Louise Lemyre holds an R.S. McLaughlin Research Chair

Hawk Eyes I: Diurnal Raptors Differ in Visual Fields and Degree of Eye Movement

BACKGROUND: Different strategies to search and detect prey may place specific demands on sensory modalities. We studied visual field configuration, degree of eye movement, and orbit orientation in three diurnal raptors belonging to the Accipitridae and Falconidae families. METHODOLOGY/PRINCIPAL FINDINGS: We used an ophthalmoscopic reflex technique and an integrated 3D digitizer system. We found inter-specific variation in visual field configuration and degree of eye movement, but not in orbit orientation. Red-tailed Hawks have relatively small binocular areas (∼33°) and wide blind areas (∼82°), but intermediate degree of eye movement (∼5°), which underscores the importance of lateral vision rather than binocular vision to scan for distant prey in open areas. Cooper's Hawks' have relatively wide binocular fields (∼36°), small blind areas (∼60°), and high degree of eye movement (∼8°), which may increase visual coverage and enhance prey detection in closed habitats. Additionally, we found that Cooper's Hawks can visually inspect the items held in the tip of the bill, which may facilitate food handling. American Kestrels have intermediate-sized binocular and lateral areas that may be used in prey detection at different distances through stereopsis and motion parallax; whereas the low degree eye movement (∼1°) may help stabilize the image when hovering above prey before an attack. CONCLUSIONS: We conclude that: (a) there are between-species differences in visual field configuration in these diurnal raptors; (b) these differences are consistent with prey searching strategies and degree of visual obstruction in the environment (e.g., open and closed habitats); (c) variations in the degree of eye movement between species appear associated with foraging strategies; and (d) the size of the binocular and blind areas in hawks can vary substantially due to eye movements. Inter-specific variation in visual fields and eye movements can influence behavioral strategies to visually search for and track prey while perching

Models of natural pest control : Towards predictions across agricultural landscapes

Natural control of invertebrate crop pests has the potential to complement or replace conventional insecticide based practices, but its mainstream application is hampered by predictive unreliability across agroecosystems. Inconsistent responses of natural pest control to changes in landscape characteristics have been attributed to ecological complexity and system-specific conditions. Here, we review agroecological models and their potential to provide predictions of natural pest control across agricultural landscapes. Existing models have used a multitude of techniques to represent specific crop-pest-enemy systems at various spatiotemporal scales, but less wealthy regions of the world are underrepresented. A realistic representation of natural pest control across systems appears to be hindered by a practical trade-off between generality and realism. Nonetheless, observations of context-sensitive, trait-mediated responses of natural pest control to land-use gradients indicate the potential of ecological models that explicitly represent the underlying mechanisms. We conclude that modelling natural pest control across agroecosystems should exploit existing mechanistic techniques towards a framework of contextually bound generalizations. Observed similarities in causal relationships can inform the functional grouping of diverse agroecosystems worldwide and the development of the respective models based on general, but context-sensitive, ecological mechanisms. The combined use of qualitative and quantitative techniques should allow the flexible integration of empirical evidence and ecological theory for robust predictions of natural pest control across a wide range of agroecological contexts and levels of knowledge availability. We highlight challenges and promising directions towards developing such a general modelling framework.Peer reviewe

An overview of animal prion diseases

Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases

Hawk Eyes II: Diurnal Raptors Differ in Head Movement Strategies When Scanning from Perches

Background Relatively little is known about the degree of inter-specific variability in visual scanning strategies in species with laterally placed eyes (e.g., birds). This is relevant because many species detect prey while perching; therefore, head movement behavior may be an indicator of prey detection rate, a central parameter in foraging models. We studied head movement strategies in three diurnal raptors belonging to the Accipitridae and Falconidae families. Methodology/Principal Findings We used behavioral recording of individuals under field and captive conditions to calculate the rate of two types of head movements and the interval between consecutive head movements. Cooper\u27s Hawks had the highest rate of regular head movements, which can facilitate tracking prey items in the visually cluttered environment they inhabit (e.g., forested habitats). On the other hand, Red-tailed Hawks showed long intervals between consecutive head movements, which is consistent with prey searching in less visually obstructed environments (e.g., open habitats) and with detecting prey movement from a distance with their central foveae. Finally, American Kestrels have the highest rates of translational head movements (vertical or frontal displacements of the head keeping the bill in the same direction), which have been associated with depth perception through motion parallax. Higher translational head movement rates may be a strategy to compensate for the reduced degree of eye movement of this species. Conclusions Cooper\u27s Hawks, Red-tailed Hawks, and American Kestrels use both regular and translational head movements, but to different extents. We conclude that these diurnal raptors have species-specific strategies to gather visual information while perching. These strategies may optimize prey search and detection with different visual systems in habitat types with different degrees of visual obstruction

Testing a TheoRY-inspired MEssage ('TRY-ME'): a sub-trial within the Ontario Printed Educational Message (OPEM) trial

<p>Abstract</p> <p>Background</p> <p>A challenge for implementation researchers is to develop principles that could generate testable hypotheses that apply across a range of clinical contexts, thus leading to generalisability of findings. Such principles may be provided by systematically developed theories. The opportunity has arisen to test some of these theoretical principles in the Ontario Printed Educational Materials (OPEM) trial by conducting a sub-trial within the existing trial structure. OPEM is a large factorial cluster-randomised trial evaluating the effects of short directive and long discursive educational messages embedded into <b><it>informed</it></b>, an evidence-based newsletter produced in Canada by the Institute for Clinical Evaluative Sciences (ICES) and mailed to all primary care physicians in Ontario. The content of educational messages in the sub-trial will be constructed using both standard methods and methods inspired by psychological theory. The aim of this study is to test the effectiveness of the TheoRY-inspired MEssage ('TRY-ME') compared with the 'standard' message in changing prescribing behaviour.</p> <p>Methods</p> <p>The OPEM trial participants randomised to receive the short directive message attached to the outside of <b><it>informed </it></b>(an 'outsert') will be sub-randomised to receive either a standard message or a message informed by the theory of planned behaviour (TPB) using a two (long insert or no insert) by three (theory-based outsert or standard outsert or no outsert) design. The messages will relate to prescription of thiazide diuretics as first line drug treatment for hypertension (described in the accompanying protocol, "The Ontario Printed Educational Materials trial"). The short messages will be developed independently by two research teams.</p> <p>The primary outcome is prescription of thiazide diuretics, measured by routinely collected data available within ICES. The study is designed to answer the question, is there any difference in guideline adherence (i.e., thiazide prescription rates) between physicians in the six groups? A process evaluation survey instrument based on the TPB will be administered pre- and post-intervention (described in the accompanying protocol, "Looking inside the black box"). The second research question concerns processes that may underlie observed differences in prescribing behaviour. We expect that effects of the messages on prescribing behaviour will be mediated through changes in physicians' cognitions.</p> <p>Trial registration number</p> <p>Current controlled trial ISRCTN72772651</p

Behavioural responses of Anopheles gambiae sensu stricto M and S molecular form larvae to an aquatic predator in Burkina Faso

Background: Predation of aquatic immature stages has been identified as a major evolutionary force driving habitat segregation and niche partitioning in the malaria mosquito Anopheles gambiae sensu stricto in the humid savannahs of Burkina Faso, West Africa. Here, we explored behavioural responses to the presence of a predator in wild populations of the M and S molecular forms of An. gambiae that typically breed in permanent (e.g., rice field paddies) and temporary (e.g., road ruts) water collections. Methods: Larvae used in these experiments were obtained from eggs laid by wild female An. gambiae collected from two localities in south-western Burkina Faso during the 2008 rainy season. Single larvae were observed in an experimental arena, and behavioural traits were recorded and quantified a) in the absence of a predator and b) in the presence of a widespread mosquito predator, the backswimmer Anisops jaczewskii. Differences in the proportion of time allocated to each behaviour were assessed using Principal Component Analysis and Multivariate Analysis of Variance. Results: The behaviour of M and S form larvae was found to differ significantly; although both forms mainly foraged at the water surface, spending 60-90% of their time filtering water at the surface or along the wall of the container, M form larvae spent on average significantly more time browsing at the bottom of the container than S form larvae (4.5 vs. 1.3% of their overall time, respectively; P < 0.05). In the presence of a predator, larvae of both forms modified their behaviour, spending significantly more time resting along the container wall (P < 0.001). This change in behaviour was at least twice as great in the M form (from 38.6 to 66.6% of the time at the wall in the absence and presence of the predator, respectively) than in the S form (from 48.3 to 64.1%). Thrashing at the water surface exposed larvae to a significantly greater risk of predation by the notonectid (P < 0.01), whereas predation occurred significantly less often when larvae were at the container wall (P < 0.05) and might reflect predator vigilance. Conclusions: Behavioural differences between larvae of the M and S form of An. gambiae in response to an acute predation risk is likely to be a reflection of different trade-offs between foraging and predator vigilance that might be of adaptive value in contrasting aquatic ecosystems. Future studies should explore the relevance of these findings under the wide range of natural settings where both forms co-exist in Africa

Genome-Wide Gene Expression Analysis in Response to Organophosphorus Pesticide Chlorpyrifos and Diazinon in C. elegans

Organophosphorus pesticides (OPs) were originally designed to affect the nervous system by inhibiting the enzyme acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Over the past years evidence is mounting that these compounds affect many other processes. Little is known, however, about gene expression responses against OPs in the nematode Caenorhabditis elegans. This is surprising because C. elegans is extensively used as a model species in toxicity studies. To address this question we performed a microarray study in C. elegans which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon, and a low dose mixture of these two compounds. Our analysis revealed transcriptional responses related to detoxification, stress, innate immunity, and transport and metabolism of lipids in all treatments. We found that for both compounds as well as in the mixture, these processes were regulated by different gene transcripts. Our results illustrate intense, and unexpected crosstalk between gene pathways in response to chlorpyrifos and diazinon in C. elegans

Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

<p>Abstract</p> <p>Background</p> <p>The genus <it>Neisseria </it>contains two important yet very different pathogens, <it>N. meningitidis </it>and <it>N. gonorrhoeae</it>, in addition to non-pathogenic species, of which <it>N. lactamica </it>is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally.</p> <p>Results</p> <p>Non-pathogenic <it>N. lactamica </it>exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal <it>cps </it>region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent.</p> <p>Conclusion</p> <p>The three <it>Neisseria </it>species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.</p