Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations

Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of BMI and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition

Dazzle Camouflage Affects Speed Perception

Movement is the enemy of camouflage: most attempts at concealment are disrupted by motion of the target. Faced with this problem, navies in both World Wars in the twentieth century painted their warships with high contrast geometric patterns: so-called “dazzle camouflage”. Rather than attempting to hide individual units, it was claimed that this patterning would disrupt the perception of their range, heading, size, shape and speed, and hence reduce losses from, in particular, torpedo attacks by submarines. Similar arguments had been advanced earlier for biological camouflage. Whilst there are good reasons to believe that most of these perceptual distortions may have occurred, there is no evidence for the last claim: changing perceived speed. Here we show that dazzle patterns can distort speed perception, and that this effect is greatest at high speeds. The effect should obtain in predators launching ballistic attacks against rapidly moving prey, or modern, low-tech battlefields where handheld weapons are fired from short ranges against moving vehicles. In the latter case, we demonstrate that in a typical situation involving an RPG7 attack on a Land Rover the reduction in perceived speed is sufficient to make the grenade miss where it was aimed by about a metre, which could be the difference between survival or not for the occupants of the vehicle

The effectiveness and cost-effectiveness of a participative community singing programme as a health promotion initiative for older people: protocol for a randomised controlled trial

Background The growth in numbers of older people represents a considerable cost to health and social care services in the United Kingdom. There is an acknowledged need to address issues of social exclusion and both the physicial and mental health of this age group. In recent years there has been much interest in the potential contribution of the arts to the health of communities and individuals. There is some evidence that participative singing may be of benefit to older people, however studies to date are limited in number and have lacked rigour. There is therefore a need to build on this knowledge base to provide more quantifiable evidence of both effectiveness and cost efffectness of singing as a health intervention of this population group. Methods The proposed study is a pragmatic randomised controlled trial with two parallel arms. The primary hypothesis is that singing groups for older people improve both physical and mental aspects of qualaity of life when compared to usual activities. Potential participants will be volunteers over 60 years living in the community and recruited through publicity. Eligible and consenting participants will be randomized to either a singing group or a control group. Singing groups will take part in a twelve week planned programme of singing and control groups will continue with usual activities. The primary outcome measure will be the York SF-12, a health related quality of life measure which will be administered at baseline, three and six months after baseline. The study will evaluate both effectiveness and cost-effectiveness. Discussion This study proposes to add to the exisiting body of evidence on the value of singing for older people by using a rigorous methodological design, which includes a power calucation, a standardised intervention and assessment of cost-effectiveness. It should be regarded as a stage in a progressive programme of studies in this area. If group singing is found to be effective and cost-effective it may offer an alternative means to maintaining the health of people in later life

The effectiveness of digital storytelling in the classrooms: a comprehensive study

In recent years the use of new technologies in educational systems has increased worldwide as digital cameras, personal computers, scanners, and easy-to-use software have become available to educators to harness the digital world. The impact of new technologies in educational contexts has been mostly positive as new technologies have given educators the opportunity to enhance their knowledge, skills, and therefore enhance the standard of education. Researchers have found that student engagement, achievement and motivation are enhanced through integration of such technologies. However, education systems still face many challenges: one of these challenges is how to enhance student engagement to provide better educational outcomes. It has become increasingly important to use innovative pedagogical models to engage learners. Digital storytelling is one of the innovative pedagogical approaches that can engage students in deep and meaningful learning. This research project aimed to create a constructivist learning environment with digital storytelling. The research investigated the pedagogical aspects of digital storytelling and the impact of digital storytelling on student learning when teachers and students use digital stories. A multi-site case study was conducted in one Australian school at primary and secondary levels. In selected classrooms, students and teachers had the opportunity to engage in innovative learning experiences based on digital storytelling. In order to enhance the reliability and validity of the research, multiple methods of data collection and analysis were used. Data was collected with qualitative and quantitative methods. An evaluation rubric was used to collect quantitative data, while interviews and observation were used to collect qualitative data. Data collection was guided by a mixed methods research design in order to evaluate if and how digital storytelling enhances teaching and learning outcomes. The findings from this study suggest that digital storytelling is a powerful tool to integrate instructional messages with learning activities to create more engaging and exciting learning environments. It is a meaningful approach for creating a constructivist learning environment based on novel principles of teaching and learning. Thus, this approach has the potential to enhance student engagement and provide better educational outcomes for learners

Follow-up of atheroma burden with sequential whole body contrast enhanced MR angiography:a feasibility study

Assess the feasibility of whole body magnetic resonance angiography (WB-MRA) for monitoring global atheroma burden in a population with peripheral arterial disease (PAD). 50 consecutive patients with symptomatic PAD referred for clinically indicated MRA were recruited. Whole body MRA (WB-MRA) was performed at baseline, 6 months and 3 years. The vasculature was split into 31 anatomical arterial segments. Each segment was scored according to degree of luminal narrowing: 0 = normal, 1 = <50 %, 2 = 50–70 %, 3 = 71–99 %, 4 = vessel occlusion. The score from all assessable segments was summed, and then normalised to the number of assessable vessels. This normalised score was divided by four (the maximum vessel score) and multiplied by 100 to give a final standardised atheroma score (SAS) with a score of 0–100. Progression was assessed with repeat measure ANOVA. 36 patients were scanned at 0 and 6 months, with 26 patients scanned at the 3 years follow up. Only those who completed all three visits were included in the final analysis. Baseline atherosclerotic burden was high with a mean SAS of 15.7 ± 10.3. No significant progression was present at 6 months (mean SAS 16.4 ± 10.5, p = 0.67), however there was significant disease progression at 3 years (mean SAS 17.7 ± 11.5, p = 0.01). Those with atheroma progression at follow-up were less likely to be on statin therapy (79 vs 100 %, p = 0.04), and had significantly higher baseline SAS (17.6 ± 11.2 vs 10.7 ± 5.1, p = 0.043). Follow up of atheroma burden is possible with WB-MRA, which can successfully quantify and monitor atherosclerosis progression at 3 years follow-up

Occupational stress, work-home interference and burnout among Belgian veterinary practitioners

There have been few formal studies on stress in veterinary surgeons and, in the rare studies available, stress is not examined jointly through the levels of job strain and job engagement, the sources of stress in the issue of work environment and the work-home interference. The authors' goal in this study was to analyse job engagement, job strain, burnout, work-home interference and job stress factors among 216 Belgian veterinary surgeons. Rural practice was compared to small animal and mixed activity. The mean job strain and job engagement level in veterinary surgeons was not higher than what we found in other working populations. However, 15.6% of the group were found to be suffering from high burnout. Rural practitioners had a lower level of job engagement than small animal veterinary surgeons. These small animal practitioners had a lower level of job strain than the mixed practitioners. The level of burnout did not differ significantly across the three types of activity. In comparison to other Belgian and Dutch workers, veterinary surgeons perceived more negative work-home interference. Bovine and mixed practitioners were the most concerned with this problem. The two most important sources of stress reported by bovine practitioners were relations to farmers and working time management (including emergencies and availability)

Recent Salmon Declines: A Result of Lost Feeding Opportunities Due to Bad Timing?

As the timing of spring productivity blooms in near-shore areas advances due to warming trends in global climate, the selection pressures on out-migrating salmon smolts are shifting. Species and stocks that leave natal streams earlier may be favoured over later-migrating fish. The low post-release survival of hatchery fish during recent years may be in part due to static release times that do not take the timing of plankton blooms into account. This study examined the effects of release time on the migratory behaviour and survival of wild and hatchery-reared coho salmon (Oncorhynchus kisutch) using acoustic and coded-wire telemetry. Plankton monitoring and near-shore seining were also conducted to determine which habitat and food sources were favoured. Acoustic tags (n = 140) and coded-wire tags (n = 266,692) were implanted into coho salmon smolts at the Seymour and Quinsam Rivers, in British Columbia, Canada. Differences between wild and hatchery fish, and early and late releases were examined during the entire lifecycle. Physiological sampling was also carried out on 30 fish from each release group. The smolt-to-adult survival of coho salmon released during periods of high marine productivity was 1.5- to 3-fold greater than those released both before and after, and the fish's degree of smoltification affected their downstream migration time and duration of stay in the estuary. Therefore, hatchery managers should consider having smolts fully developed and ready for release during the peak of the near-shore plankton blooms. Monitoring chlorophyll a levels and water temperature early in the spring could provide a forecast of the timing of these blooms, giving hatcheries time to adjust their release schedule

Tailored vs. Standardized Internet-Based Cognitive Behavior Therapy for Depression and Comorbid Symptoms: A Randomized Controlled Trial

Background and Aims:Major depression can be treated by means of cognitive behavior therapy, delivered via the Internet as guided self-help. Individually tailored guided self-help treatments have shown promising results in the treatment of anxiety disorders. This randomized controlled trial tested the efficacy of an Internet-based individually tailored guided selfhelp treatment which specifically targeted depression with comorbid symptoms. The treatment was compared both to standardized (non-tailored) Internet-based treatment and to an active control group in the form of a monitored online discussion group. Both guided self-help treatments were based on cognitive behavior therapy and lasted for 10 weeks. The discussion group consisted of weekly discussion themes related to depression and the treatment of depression. Methods:A total of 121 participants with diagnosed major depressive disorder and with a range of comorbid symptoms were randomized to three groups. The tailored treatment consisted of a prescribed set of modules targeting depression as well as comorbid problems. The standardized treatment was a previously tested guided self-help program for depression. Results:From pre-treatment to post-treatment, both treatment groups improved on measures of depression, anxiety and quality of life. The results were maintained at a 6-month follow-up. Subgroup analyses showed that the tailored treatment was more effective than the standardized treatment among participants with higher levels of depression at baseline and more comorbidity, both in terms of reduction of depressive symptoms and on recovery rates. In the subgroup with lower baseline scores of depression, few differences were seen between treatments and the discussion group. Conclusions:This study shows that tailored Internet-based treatment for depression is effective and that addressing comorbidity by tailoring may be one way of making guided self-help treatments more effective than standardized approaches in the treatment of more severe depression