Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

<p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt

Learning to teach data journalism: Innovation, influence and constraints

Journalism education has tended to respond slowly to developments in digital journalism, such as data journalism, despite or because of close links with the industry. This paper examines the obstacles to innovation in journalism education with particular reference to data journalism, drawing on the literature, a review of stakeholders and course documents, and the author’s reflections on developing a data journalism module as part of a new MA programme. It highlights the complexities linked to the particular demands of data journalism, and identifies critical issues around student satisfaction; reputation and job/career outcomes; relevance, currency and appeal; programme management; and coherence. Rather than holding it back, more specialized socialization could assist journalism education to innovate effectively, the author suggests

Metabolic, hygric and ventilatory physiology of a hypermetabolic marsupial, the honey possum (Tarsipes rostratus)

The honey possum is the only non-volant mammal to feed exclusively on a diet of nectar and pollen. Like other mammalian and avian nectarivores, previous studies indicated that the honey possum's basal metabolic rate was higher than predicted for a marsupial of equivalent body mass. However, these early measurements have been questioned. We re-examined the basal metabolic rate (2.52 +/- A 0.222 ml O(2) g(-1) h(-1)) of the honey possum and confirm that it is indeed higher (162%) than predicted for other marsupials both before and after accounting for phylogenetic history. This, together with its small body mass (5.4 +/- A 0.14 g; 1.3% of that predicted by phylogeny) may be attributed to its nectarivorous diet and mesic distribution. Its high-basal metabolic rate is associated with a high-standard body temperature (36.6 +/- A 0.48A degrees C) and oxygen extraction (19.4%), but interestingly the honey possum has a high point of relative water economy (17.0A degrees C) and its standard evaporative water loss (4.33 +/- A 0.394 mg H(2)O g(-1) h(-1)) is not elevated above that of other marsupials, despite its mesic habitat and high dietary water intake.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The Impact of HIV, an Antiretroviral Programme and Tuberculosis on Mortality in South African Platinum Miners, 1992–2010

HIV and tuberculosis (TB) are the most common causes of death in South Africa. Antiretroviral therapy (ART) programmes should have had an impact on mortality rates. This study describes the impact of HIV, a Wellness (HIV/ART) programme and TB on population-wide trends in mortality and causes of death among South African platinum miners, from before the HIV epidemic into the ART era

Polymicrobial Nature of Chronic Diabetic Foot Ulcer Biofilm Infections Determined Using Bacterial Tag Encoded FLX Amplicon Pyrosequencing (bTEFAP)

Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections. spp. and against difficult to culture bacteria such as anaerobes. While PCR methods also have bias, further work is now needed in comparing traditional culture results to high-resolution molecular diagnostic methods such as bTEFAP

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record

Involvement of the V2 Vasopressin Receptor in Adaptation to Limited Water Supply

Mammals adapted to a great variety of habitats with different accessibility to water. In addition to changes in kidney morphology, e.g. the length of the loops of Henle, several hormone systems are involved in adaptation to limited water supply, among them the renal-neurohypophysial vasopressin/vasopressin receptor system. Comparison of over 80 mammalian V2 vasopressin receptor (V2R) orthologs revealed high structural and functional conservation of this key component involved in renal water reabsorption. Although many mammalian species have unlimited access to water there is no evidence for complete loss of V2R function indicating an essential role of V2R activity for survival even of those species. In contrast, several marsupial V2R orthologs show a significant increase in basal receptor activity. An increased vasopressin-independent V2R activity can be interpreted as a shift in the set point of the renal-neurohypophysial hormone circuit to realize sufficient water reabsorption already at low hormone levels. As found in other desert mammals arid-adapted marsupials show high urine osmolalities. The gain of basal V2R function in several marsupials may contribute to the increased urine concentration abilities and, therefore, provide an advantage to maintain water and electrolyte homeostasis under limited water supply conditions

Long-term species, sexual and individual variations in foraging strategies of fur seals revealed by stable isotopes in whiskers

Background: Individual variations in the use of the species niche are an important component of diversity in trophic interactions. A challenge in testing consistency of individual foraging strategy is the repeated collection of information on the same individuals. Methodology/Principal Findings: The foraging strategies of sympatric fur seals (Arctocephalus gazella and A. tropicalis) were examined using the stable isotope signature of serially sampled whiskers. Most whiskers exhibited synchronous delta C-13 and delta N-15 oscillations that correspond to the seal annual movements over the long term (up to 8 years). delta C-13 and delta N-15 values were spread over large ranges, with differences between species, sexes and individuals. The main segregating mechanism operates at the spatial scale. Most seals favored foraging in subantarctic waters (where the Crozet Islands are located) where they fed on myctophids. However, A. gazella dispersed in the Antarctic Zone and A. tropicalis more in the subtropics. Gender differences in annual time budget shape the seal movements. Males that do not perform any parental care exhibited large isotopic oscillations reflecting broad annual migrations, while isotopic values of females confined to a limited foraging range during lactation exhibited smaller changes. Limited inter-individual isotopic variations occurred in female seals and in male A. tropicalis. In contrast, male A. gazella showed large inter-individual variations, with some males migrating repeatedly to high-Antarctic waters where they fed on krill, thus meaning that individual specialization occurred over years. Conclusions/Significance: Whisker isotopic signature yields unique long-term information on individual behaviour that integrates the spatial, trophic and temporal dimensions of the ecological niche. The method allows depicting the entire realized niche of the species, including some of its less well-known components such as age-, sex-, individual- and migration-related changes. It highlights intrapopulation heterogeneity in foraging strategies that could have important implications for likely demographic responses to environmental variability

Toward a Theory of Child Well-Being

Assuring the well-being of children has emerged over the past several decades as an important goal for health and social policymakers. Although the concept of child well-being has been operationalized and measured in different ways by different child-serving entities, there are few unifying theories that could undergird and inform these various conceptual and measurement efforts. In this paper, we attempt to construct a theory of child well-being. We first review the social and policy history of the concept of child well-being, and briefly review its measurement based on these conceptualizations. We then examine three types of theories of well-being extant in philosophy - mental states theories, desire-based theories and needs-based theories - and investigate their suitability to serve as prototypes of a theory of child well-being. We develop a constraint that child well-being is important in and of itself and not merely as a way station to future adult well-being (we call this a non-reduction constraint). Using this constraint, we identify the limitations of each of the three sets of theories to serve as a basis for a theory of child well-being. Based on a developmentalist approach, we then articulate a theory of child well-being that contains two conditions. First, a child's stage-appropriate capacities that equip her for successful adulthood, given her environment; and, second, an engagement with the world in child-appropriate ways. We conclude by reviewing seven implications of this theoretical approach for the measurement of child well-being. Key Words Child well-being, philosophy, social policy, child developmentNoneThis is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11205-014-0665-

Human–agent collaboration for disaster response

In the aftermath of major disasters, first responders are typically overwhelmed with large numbers of, spatially distributed, search and rescue tasks, each with their own requirements. Moreover, responders have to operate in highly uncertain and dynamic environments where new tasks may appear and hazards may be spreading across the disaster space. Hence, rescue missions may need to be re-planned as new information comes in, tasks are completed, or new hazards are discovered. Finding an optimal allocation of resources to complete all the tasks is a major computational challenge. In this paper, we use decision theoretic techniques to solve the task allocation problem posed by emergency response planning and then deploy our solution as part of an agent-based planning tool in real-world field trials. By so doing, we are able to study the interactional issues that arise when humans are guided by an agent. Specifically, we develop an algorithm, based on a multi-agent Markov decision process representation of the task allocation problem and show that it outperforms standard baseline solutions. We then integrate the algorithm into a planning agent that responds to requests for tasks from participants in a mixed-reality location-based game, called AtomicOrchid, that simulates disaster response settings in the real-world. We then run a number of trials of our planning agent and compare it against a purely human driven system. Our analysis of these trials show that human commanders adapt to the planning agent by taking on a more supervisory role and that, by providing humans with the flexibility of requesting plans from the agent, allows them to perform more tasks more efficiently than using purely human interactions to allocate tasks. We also discuss how such flexibility could lead to poor performance if left unchecked