Extensible Modeling and Simulation Framework (XMSF) Opportunities for Web-Based Modeling and Simulation

Technical Opportunities Workshop Whitepaper, 14 June 2002Purpose: As the Department of Defense (DoD) is engaged in both warfighting and institutional transformation for the new millennium, DoD Modeling & Simulation (M&S) also needs to identify and adopt transformational technologies which provide direct tactical relevance to warfighters. Because the only software systems that composably scale to worldwide scope utilize the World Wide Web, it is evident that an extensible Web-based framework shows great promise to scale up the capabilities of M&S systems to meet the needs of training, analysis, acquisition, and the operational warfighter. By embracing commercial web technologies as a shared-communications platform and a ubiquitous-delivery framework, DoD M&S can fully leverage mainstream practices for enterprise-wide software development

Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease

The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a unique bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Pervasiveness of Parasites in Pollinators

Many pollinator populations are declining, with large economic and ecological implications. Parasites are known to be an important factor in the some of the population declines of honey bees and bumblebees, but little is known about the parasites afflicting most other pollinators, or the extent of interspecific transmission or vectoring of parasites. Here we carry out a preliminary screening of pollinators (honey bees, five species of bumblebee, three species of wasp, four species of hoverfly and three genera of other bees) in the UK for parasites. We used molecular methods to screen for six honey bee viruses, Ascosphaera fungi, Microsporidia, and Wolbachia intracellular bacteria. We aimed simply to detect the presence of the parasites, encompassing vectoring as well as actual infections. Many pollinators of all types were positive for Ascosphaera fungi, while Microsporidia were rarer, being most frequently found in bumblebees. We also detected that most pollinators were positive for Wolbachia, most probably indicating infection with this intracellular symbiont, and raising the possibility that it may be an important factor in influencing host sex ratios or fitness in a diversity of pollinators. Importantly, we found that about a third of bumblebees (Bombus pascuorum and Bombus terrestris) and a third of wasps (Vespula vulgaris), as well as all honey bees, were positive for deformed wing virus, but that this virus was not present in other pollinators. Deformed wing virus therefore does not appear to be a general parasite of pollinators, but does interact significantly with at least three species of bumblebee and wasp. Further work is needed to establish the identity of some of the parasites, their spatiotemporal variation, and whether they are infecting the various pollinator species or being vectored. However, these results provide a first insight into the diversity, and potential exchange, of parasites in pollinator communities

Immediate versus sustained effects: interrupted time series analysis of a tailored intervention

Background: Detailed intervention descriptions and robust evaluations that test intervention impact—and explore reasons for impact—are an essential part of progressing implementation science. Time series designs enable the impact and sustainability of intervention effects to be tested. When combined with time series designs, qualitative methods can provide insight into intervention effectiveness and help identify areas for improvement for future interventions. This paper describes the development, delivery, and evaluation of a tailored intervention designed to increase primary health care professionals’ adoption of a national recommendation that women with mild to moderate postnatal depression (PND) are referred for psychological therapy as a first stage treatment. Methods: Three factors influencing referral for psychological treatment were targeted using three related intervention components: a tailored educational meeting, a tailored educational leaflet, and changes to an electronic system data template used by health professionals during consultations for PND. Evaluation comprised time series analysis of monthly audit data on percentage referral rates and monthly first prescription rates for anti-depressants. Interviews were conducted with a sample of health professionals to explore their perceptions of the intervention components and to identify possible factors influencing intervention effectiveness. Results: The intervention was associated with a significant, immediate, positive effect upon percentage referral rates for psychological treatments. This effect was not sustained over the ten month follow-on period. Monthly rates of anti-depressant prescriptions remained consistently high after the intervention. Qualitative interview findings suggest key messages received from the intervention concerned what appropriate antidepressant prescribing is, suggesting this to underlie the lack of impact upon prescribing rates. However, an understanding that psychological treatment can have long-term benefits was also cited. Barriers to referral identified before intervention were cited again after the intervention, suggesting the intervention had not successfully tackled the barriers targeted. Conclusion: A time series design allowed the initial and sustained impact of our intervention to be tested. Combined with qualitative interviews, this provided insight into intervention effectiveness. Future research should test factors influencing intervention sustainability, and promote adoption of the targeted behavior and dis-adoption of competing behaviors where appropriate

Evolution of Genome Size and Complexity in Pinus

BACKGROUND: Genome evolution in the gymnosperm lineage of seed plants has given rise to many of the most complex and largest plant genomes, however the elements involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Gymny is a previously undescribed retrotransposon family in Pinus that is related to Athila elements in Arabidopsis. Gymny elements are dispersed throughout the modern Pinus genome and occupy a physical space at least the size of the Arabidopsis thaliana genome. In contrast to previously described retroelements in Pinus, the Gymny family was amplified or introduced after the divergence of pine and spruce (Picea). If retrotransposon expansions are responsible for genome size differences within the Pinaceae, as they are in angiosperms, then they have yet to be identified. In contrast, molecular divergence of Gymny retrotransposons together with other families of retrotransposons can account for the large genome complexity of pines along with protein-coding genic DNA, as revealed by massively parallel DNA sequence analysis of Cot fractionated genomic DNA. CONCLUSIONS/SIGNIFICANCE: Most of the enormous genome complexity of pines can be explained by divergence of retrotransposons, however the elements responsible for genome size variation are yet to be identified. Genomic resources for Pinus including those reported here should assist in further defining whether and how the roles of retrotransposons differ in the evolution of angiosperm and gymnosperm genomes

Food for pollinators: quantifying the nectar and pollen resources of urban flower meadows

Planted meadows are increasingly used to improve the biodiversity and aesthetic amenity value of urban areas. Although many ‘pollinator-friendly’ seed mixes are available, the floral resources these provide to flower-visiting insects, and how these change through time, are largely unknown. Such data are necessary to compare the resources provided by alternative meadow seed mixes to each other and to other flowering habitats. We used quantitative surveys of over 2 million flowers to estimate the nectar and pollen resources offered by two exemplar commercial seed mixes (one annual, one perennial) and associated weeds grown as 300m2 meadows across four UK cities, sampled at six time points between May and September 2013. Nectar sugar and pollen rewards per flower varied widely across 65 species surveyed, with native British weed species (including dandelion, Taraxacum agg.) contributing the top five nectar producers and two of the top ten pollen producers. Seed mix species yielding the highest rewards per flower included Leontodon hispidus, Centaurea cyanus and C. nigra for nectar, and Papaver rhoeas, Eschscholzia californica and Malva moschata for pollen. Perennial meadows produced up to 20x more nectar and up to 6x more pollen than annual meadows, which in turn produced far more than amenity grassland controls. Perennial meadows produced resources earlier in the year than annual meadows, but both seed mixes delivered very low resource levels early in the year and these were provided almost entirely by native weeds. Pollen volume per flower is well predicted statistically by floral morphology, and nectar sugar mass and pollen volume per unit area are correlated with flower counts, raising the possibility that resource levels can be estimated for species or habitats where they cannot be measured directly. Our approach does not incorporate resource quality information (for example, pollen protein or essential amino acid content), but can easily do so when suitable data exist. Our approach should inform the design of new seed mixes to ensure continuity in floral resource availability throughout the year, and to identify suitable species to fill resource gaps in established mixes

Influence of exercise intensity on training-induced tendon mechanical properties changes in older individuals

This study compared the effects of low vs. high intensity training on tendon properties in an elderly population. Participants were pair-matched (gender, habitual physical activity, anthropometrics, and baseline knee extension strength) and then randomly assigned to low (LowR, i.e., ∼40 % 1RM) or high (High R, i.e., ∼80 % 1RM) intensity resistance training programmes for 12 weeks, 3x per week (LowR, n = 9, age 74 ± 5 years; HighR, n = 8, age 68 ± 6 years). Patellar tendon properties (stiffness [K], Young's modulus [YM], cross-sectional area [T CSA], and tendon length [T L]) were measured pre and post training using a combination of magnetic resonance imaging (MRI), B-mode ultrasonography, dynamometry, electromyography and ramped isometric knee extensions. With training K showed no significant change in the LowR group while it incremented by 57.7 % in the HighR group (p < 0.05). The 51.1 % group difference was significant (p < 0.05). These differences were still apparent when the data was normalized for T CSA and T L, i.e., significant increase in YM post-intervention in HighR (p < 0.05), but no change in LowR. These findings suggest that when prescribing exercise for a mixed genders elderly population, exercise intensities of ≤40 % 1RM may not be sufficient to affect tendon properties. © 2014 American Aging Association