Modelling Marek's Disease Virus (MDV) infection: parameter estimates for mortality rate and infectiousness

Background: Marek's disease virus (MDV) is an economically important oncogenic herpesvirus of poultry. Since the 1960s, increasingly virulent strains have caused continued poultry industry production losses worldwide. To understand the mechanisms of this virulence evolution and to evaluate the epidemiological consequences of putative control strategies, it is imperative to understand how virulence is defined and how this correlates with host mortality and infectiousness during MDV infection. We present a mathematical approach to quantify key epidemiological parameters. Host lifespan, virus latent periods and host viral shedding rates were estimated for unvaccinated and vaccinated birds, infected with one of three MDV strains. The strains had previously been pathotyped to assign virulence scores according to pathogenicity of strains in hosts. Results: Our analyses show that strains of higher virulence have a higher viral shedding rate, and more rapidly kill hosts. Vaccination enhances host life expectancy but does not significantly reduce the shedding rate of the virus. While the primary latent period of the virus does not vary with challenge strain nor vaccine treatment of host, the time until the maximum viral shedding rate is increased with vaccination. Conclusions: Our approach provides the tools necessary for a formal analysis of the evolution of virulence in MDV, and potentially simpler and cheaper approaches to comparing the virulence of MDV strains

Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review

Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma

Exploring Older Adult Susceptibility to Fraudulent Computer Pop-Up Interruptions

© 2019, Springer International Publishing AG, part of Springer Nature. The proliferation of Internet connectivity and accessibility has been accompanied by an increase in cyber-threats, including fraudulent communications. Fake computer updates, which attempt to persuade people to download malicious software by mimicking trusted brands and/or instilling urgency, are one way in which fraudsters try to infiltrate systems. A recent study of young university students (M 18.52-years) found that when such pop-ups interrupt a demanding cognitive task, participants spent little time viewing them and were more likely to miss suspicious cues and accept these updates compared to when they were viewed without the pressure to resume a suspended task [1]. The aim of the current experiment was to test an older adult sample (N = 29, all >60 years) using the same paradigm. We predicted that they would be more susceptible to malevolent pop-ups [2]; trusting them more than younger adults (e.g., [3]), and would attempt to resume the interrupted task faster to limit forgetting of encoded items. Phase 1 involved serial recall memory trials interrupted by genuine, mimicked, and low authority pop-ups. During phase 2, participants rated messages with unlimited time and gave reasons for their decisions. It was found that more than 70% of mimicked and low authority pop-ups were accepted in Phase 1 vs ~80% genuine pop-ups (and these were all approximately 10% higher than [1]). This was likely due to a greater tendency to ignore or miss suspicious content when performing under pressure, despite spending longer with messages and reporting high awareness of scam techniques than younger adults. Older adult participants were more suspicious during Phase 2 performing comparably to the younger adults in [1]. Factors that may impact older adult decisions relating to fraudulent computer communications are discussed, as well as theoretical and practical implications

Evidence-Based Mental Health Programs in Schools: Barriers and Facilitators of Successful Implementation

Although schools can improve children’s access to mental health services, not all school-based providers are able to successfully deliver evidence-based practices. Indeed, even when school clinicians are trained in evidence-based practices (EBP), the training does not necessarily result in the implementation of those practices. This study explores factors that influence implementation of a particular EBP, Cognitive Behavioral Intervention for Trauma in Schools (CBITS). Semi-structured telephone interviews with 35 site administrators and clinicians from across the United States were conducted 6–18 months after receiving CBITS training to discuss implementation experiences. The implementation experiences of participants differed, but all reported similar barriers to implementation. Sites that successfully overcame such barriers differed from their unsuccessful counterparts by having greater organizational structure for delivering school services, a social network of other clinicians implementing CBITS, and administrative support for implementation. This study suggests that EBP implementation can be facilitated by having the necessary support from school leadership and peers

Safety of low-carbohydrate diets

Low-carbohydrate diets have re-emerged into the public spotlight and are enjoying a high degree of popularity as people search for a solution to the population\u27s ever-expanding waistline. The current evidence though indicates that low-carbohydrate diets present no significant advantage over more traditional energy-restricted diets on long-term weight loss and maintenance. Furthermore, a higher rate of adverse side-effects can be attributed to low-carbohydrate dieting approaches. Short-term efficacy of low-carbohydrate diets has been demonstrated for some lipid parameters of cardiovascular risk and measures of glucose control and insulin sensitivity, but no studies have ascertained if these effects represent a change in primary outcome measures. Low-carbohydrate diets are likely effective and not harmful in the short term and may have therapeutic benefits for weight-related chronic diseases although weight loss on such a program should be undertaken under medical supervision. While new commercial incarnations of the low-carbohydrate diet are now addressing overall dietary adequacy by encouraging plenty of high-fibre vegetables, fruit, low-glycaemic-index carbohydrates and healthier fat sources, this is not the message that reaches the entire public nor is it the type of diet adopted by many people outside of the world of a well-designed clinical trial. Health effects of long-term ad hoc restriction of inherently beneficial food groups without a concomitant reduction in body weight remains unanswered.<br /

A guide to using the Theoretical Domains Framework of behaviour change to investigate implementation problems

Background: Implementing new practices requires changes in the behaviour of relevant actors, and this is facilitated by understanding of the determinants of current and desired behaviours. The Theoretical Domains Framework (TDF) was developed by a collaboration of behavioural scientists and implementation researchers who identified theories relevant to implementation and grouped constructs from these theories into domains. The collaboration aimed to provide a comprehensive, theory-informed approach to identify determinants of behaviour. The first version was published in 2005, and a subsequent version following a validation exercise was published in 2012. This guide offers practical guidance for those who wish to apply the TDF to assess implementation problems and support intervention design. It presents a brief rationale for using a theoretical approach to investigate and address implementation problems, summarises the TDF and its development, and describes how to apply the TDF to achieve implementation objectives. Examples from the implementation research literature are presented to illustrate relevant methods and practical considerations. Methods: Researchers from Canada, the UK and Australia attended a 3-day meeting in December 2012 to build an international collaboration among researchers and decision-makers interested in the advancing use of the TDF. The participants were experienced in using the TDF to assess implementation problems, design interventions, and/or understand change processes. This guide is an output of the meeting and also draws on the a uthors' collective experience. Examples from the implementation research literature judged by authors to be representative of specific applications of the TDF are included in this guide. Results: We explain and illustrate methods, with a focus on qualitative approaches, for selecting and specifying target behaviours key to implementation, selecting the study design, deciding the sampling strategy, developing study materials, collecting and analysing data, and reporting findings of TDF-based studies. Areas for development include methods for triangulating data, e.g. from interviews, questionnaires and observation and methods for designing interventions based on TDF-based problem analysis. Conclusions: We offer this guide to the implementation community to assist in the application of the TDF to achieve implementation objectives. Benefits of using the TDF include the provision of a theoretical basis for implementation studies, good coverage of potential reasons for slow diffusion of evidence into practice and a method for progressing from theory-based investigation to intervention

The sinus tarsi approach in displaced intra-articular calcaneal fractures: a systematic review

Purpose: Although open reduction and internal fixation is currently considered the gold standard in surgical treatment of displaced intra-articular calcaneal fractures, various different approaches exist including the limited lateral approach. The aim of this systematic review was to combine the results of studies using the sinus tarsi approach, which is the most frequently applied limited lateral approach. Method: A literature search in the electronic databases of the Cochrane Library and Pubmed Medline, between January 1st 2000 to December 1st 2010, was conducted to identify studies in which the sinus tarsi approach or a modified sinus tarsi approach was utilized for the treatment of displaced intra-articular calcaneal fractures. The methodological quality of the included studies was assessed using the Coleman methodology score. Results: A total of eight case series reporting on 256 patients with 271 calcaneal fractures was identified. Overall good to excellent outcome was reached in three-quarters of all patients. An average complication rate of minor wound complications of 4.1% was reported and major wound complications in 0.7%. The need for a secondary subtalar arthrodesis occurred at an average rate of 4.3%. The average Coleman methodology score was 56.8 (range 39-72) points. Conclusion: The results, i.e. functional outcome and complication rates, of the sinus tarsi approach compare similarly or favourably to the extended lateral approach. Therefore, in the process of tailoring the best treatment modality to the right patient and the right fracture type, the sinus tarsi approach might be a valuable asset

Asymmetric recurrent laryngeal nerve conduction velocities and dorsal cricoarytenoid muscle electromyographic characteristics in clinically normal horses

The dorsal cricoarytenoid (DCA) muscles, are a fundamental component of the athletic horse’s respiratory system: as the sole abductors of the airways, they maintain the size of the rima glottis which is essential for enabling maximal air intake during intense exercise. Dysfunction of the DCA muscle leads to arytenoid collapse during exercise, resulting in poor performance. An electrodiagnostic study including electromyography of the dorsal cricoarytenoid muscles and conduction velocity testing of the innervating recurrent laryngeal nerves (RLn) was conducted in horses with normal laryngeal function. We detected reduced nerve conduction velocity of the left RLn, compared to the right, and pathologic spontaneous activity (PSA) of myoelectrical activity within the left DCA muscle in half of this horse population and the horses with the slowest nerve conduction velocities. The findings in this group of horses are consistent with left sided demyelination and axonal loss, consistent with Recurrent Laryngeal Neuropathy (RLN), a highly prevalent degenerative disorder of the RLn in horses that predominantly affects the left side. The detection of electromyographic changes compatible with RLN in clinically unaffected horses is consistent with previous studies that identified “subclinical” subjects, presenting normal laryngeal function despite neuropathologic changes within nerve and muscle confirmed histologically

Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Interleukin-2 (IL-2) induces durable objective responses in a small cohort of patients with metastatic renal cell carcinoma (RCC) but the antigen(s) responsible for tumor rejection are not known. 5T4 is a non-secreted membrane glycoprotein expressed on clear cell and papillary RCCs. A modified vaccinia virus Ankara (MVA) encoding 5T4 was tested in combination with high-dose IL-2 to determine the safety, objective response rate and effect on humoral and cell-mediated immunity.</p> <p>Methods</p> <p>25 patients with metastatic RCC who qualified for IL-2 were eligible and received three immunizations every three weeks followed by IL-2 (600,000 IU/kg) after the second and third vaccinations. Blood was collected for analysis of humoral, effector and regulatory T cell responses.</p> <p>Results</p> <p>There were no serious vaccine-related adverse events. While no objective responses were observed, three patients (12%) were rendered disease-free after nephrectomy or resection of residual metastatic disease. Twelve patients (48%) had stable disease which was associated with improved median overall survival compared to patients with progressive disease (not reached vs. 28 months, p = 0.0261). All patients developed 5T4-specific antibody responses and 13 patients had an increase in 5T4-specific T cell responses. Although the baseline frequency of Tregs was elevated in all patients, those with stable disease showed a trend toward increased effector CD8+ T cells and a decrease in Tregs.</p> <p>Conclusion</p> <p><b>V</b>accination with MVA-5T4 did not improve objective response rates of IL-2 therapy but did result in stable disease associated with an increase in the ratio of 5T4-specific effector to regulatory T cells in selected patients.</p> <p>Trial registration number</p> <p>ISRCTN83977250</p