Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Integrating research- and relationship-based approaches in Australian health promotion practice

We examine the perspectives of health promotion practitioners on their approaches to determining health promotion practice, in particular on the role of research and relationships in this process. Using Grounded Theory methods, we analysed 58 semi-structured interviews with 54 health promotion practitioners in New South Wales, Australia. Practitioners differentiated between relationship-based and research-based approaches as two sources of knowledge to guide health promotion practice. We identify several tensions in seeking to combine these approaches in practice and describe the strategies that participants adopted to manage these tensions. The strategies included working in an evidence-informed rather than evidence-based way, creating new evidence about relationship-based processes and outcomes, adopting ‘relationship-based’ research and evaluation methods, making research and evaluation useful for communities, building research and evaluation skills and improving collaboration between research & evaluation and program implementation staff. We conclude by highlighting three systemic factors which could further support the integration of researchbased and relationship-based health promotion practices: (1) expanding conceptions of health promotion evidence, (2) developing 'relationship-based' research methods that enable practitioners to measure complex social processes and outcomes and to facilitate community participation and benefit, and (3) developing organisational capacity. KEYWORDS: qualitative research, health promotion practice, community participation, research & evaluationNHMR

Quasi-phase-matched high-order harmonic generation using tunable pulse trains

A simple technique for generating trains of ultrafast pulses is demonstrated in which the linear separation between pulses can be varied continuously over a wide range. These pulse trains are used to achieve tunable quasi-phase-matching of high harmonic generation over a range of harmonic orders up to the harmonic cut-off, resulting in enhancements of the harmonic intensity in excess of an order of magnitude. The peak enhancement depends on the separation between pulses, as well as the number of pulses in the train, representing an easily tunable source of quasi-phase-matched high harmonic generation

An invitation to use craigslist ads to recruit respondents from stigmatized groups for qualitative interviews

Craigslist.org is a website devoted to classified advertisements as well as discussion forums with locations in more than 700 sites in 70 countries. At an estimated 30 billion page views per month and more than 50 million new classified ads posted monthly, craigslist ads have the ability to reach a wide audience. Although wildly popular, no studies to date have investigated the use of craigslist ads for qualitative research study recruitment. In this research note, I offer my own experiences from 2011 to 2012 using craigslist ads (N = 77) to recruit obese respondents (N = 38) for qualitative interviews in one major metro area in the southern United States. I also discuss some advantages and limitations of using craigslist as a recruitment tool. Overall, I invite social science researchers to consider craigslist as an innovative tool to recruit respondents for qualitative research.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

NSAID and other analgesic use by endurance runners during training, competition and recovery

Background. An increasing popularity of ultra-endurance events coupled with excessive or inappropriate non-steroidal anti-inflammatory drug (NSAID) use during such events could pose considerable potential risks to runners’ health.Objective. To evaluate the incidence of NSAID and other analgesic use in distance runners during training, competition and recovery.Methods. We performed an observational cross-sectional study at the Desert Race Across the Sand race (Colorado to Utah, USA) in June 2011 and the Empire State Marathon half-marathon, and relay races in Syracuse, NY, October 2011. A total of 27 ultramarathon runners and 46 marathon, half-marathon and marathon relay runners participated in the study. Surveys were distributed to runners during race registration. Self-reported use of common analgesic medications during training, racing and recovery was assessed.Results. Among all runners at all stages, NSAIDs were the most commonly used analgesic medication. NSAID use by ultramarathon runners compared with all other runners was similar during training (59% and 63%, respectively; χ2=0.008; p=0.93) and recovery (59% and 61%, respectively; χ2=0.007; p=0.93). However, ultramarathon runners were more likely than all other runners to use NSAIDs during the race (70% and 26%, respectively; χ2=11.76; p=0.0006).Conclusion. Despite undesirable side-effects associated with the use of NSAIDs, there was a high prevalence of use in all runners, particularly during training and recovery. NSAID use during the race was significantly greater in ultramarathon runners. Medical staff at endurance events need to be aware of, and prepared for potential complications related to the high use of NSAIDs in runners. Future efforts should focus on teaching runners about the undesirable effects of medication and emphasising alternatives to pain medication

Delayed reperfusion deficits after experimental stroke account for increased pathophysiology.

Cerebral blood flow and oxygenation in the first few hours after reperfusion following ischemic stroke are critical for therapeutic interventions but are not well understood. We investigate changes in oxyhemoglobin (HbO(2)) concentration in the cortex during and after ischemic stroke, using multispectral optical imaging in anesthetized mice, a remote filament to induce either 30 minute middle cerebral artery occlusion (MCAo), sham surgery or anesthesia alone. Immunohistochemistry establishes cortical injury and correlates the severity of damage with the change of oxygen perfusion. All groups were imaged for 6 hours after MCAo or sham surgery. Oxygenation maps were calculated using a pathlength scaling algorithm. The MCAo group shows a significant drop in HbO(2) during occlusion and an initial increase after reperfusion. Over the subsequent 6 hours HbO(2) concentrations decline to levels below those observed during stroke. Platelets, activated microglia, interleukin-1α, evidence of BBB breakdown and neuronal stress increase within the stroked hemisphere and correlate with the severity of the delayed reperfusion deficit but not with the ΔHbO(2) during stroke. Despite initial restoration of HbO(2) after 30 min MCAo there is a delayed compromise that coincides with inflammation and could be a target for improved stroke outcome after thrombolysis

Optimised XUV holography using spatially shaped high harmonic beams

A phase-only spatial light modulator is used to generate multiple infrared foci, the positions and intensities of which can be controlled programmably, allowing the generation and control of multiple high harmonic beams. Using two such high harmonic beams Fourier transform holography is performed with separate illumination of the object and reference pinhole, making optimal use of the available photon flux. This technique provides new opportunities for imaging at extreme ultraviolet wavelengths

Post-trial follow-up methodology in large randomised controlled trials: a systematic review.

BACKGROUND: Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer). METHODS: A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised controlled trials (more than 1000 adult participants) published from March 2006 to April 2017 were evaluated. Two reviewers screened and extracted data attaining > 95% concordance of papers checked. Assessment of bias in the trials was evaluated using the Cochrane Risk of Bias tool. RESULTS: Fifty-seven thousand three hundred and fifty-two papers were identified and 65 trials which had post-trial follow-up (PTFU) were included in the analysis. The majority of trials used more than one type of follow-up. There was no evidence of an association between the retention rates of participants in the PTFU period and the type of follow-up used. Costs of PTFU varied widely with data linkage being the most economical. It was not possible to assess associations between risk of bias during the in-trial period and proportions lost to follow-up during the PTFU period. DISCUSSION: Data captured during the post-trial follow-up period can add scientific value to a trial. However, there are logistical and financial barriers to overcome. Where available, data linkage via electronic registries and records is a cost-effective method which can provide data on a range of endpoints. SYSTEMATIC REVIEW REGISTRATION: Not applicable for PROSPERO registration

Decentralized Estimation over Orthogonal Multiple-access Fading Channels in Wireless Sensor Networks - Optimal and Suboptimal Estimators

Optimal and suboptimal decentralized estimators in wireless sensor networks (WSNs) over orthogonal multiple-access fading channels are studied in this paper. Considering multiple-bit quantization before digital transmission, we develop maximum likelihood estimators (MLEs) with both known and unknown channel state information (CSI). When training symbols are available, we derive a MLE that is a special case of the MLE with unknown CSI. It implicitly uses the training symbols to estimate the channel coefficients and exploits the estimated CSI in an optimal way. To reduce the computational complexity, we propose suboptimal estimators. These estimators exploit both signal and data level redundant information to improve the estimation performance. The proposed MLEs reduce to traditional fusion based or diversity based estimators when communications or observations are perfect. By introducing a general message function, the proposed estimators can be applied when various analog or digital transmission schemes are used. The simulations show that the estimators using digital communications with multiple-bit quantization outperform the estimator using analog-and-forwarding transmission in fading channels. When considering the total bandwidth and energy constraints, the MLE using multiple-bit quantization is superior to that using binary quantization at medium and high observation signal-to-noise ratio levels

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting