Evaluating the Effect of Integrated System Health Management on Mission Effectiveness

This research used systems architecture to develop a model that determined the effect of Integrated System Health Management (ISHM) on mission success rates for unmanned aerial systems (UAS). To evaluate this effect, a simulation model was developed and used to analyze the difference between mission success rates for a theoretical UAS with and without ISHM. Design of Experiments analysis techniques were used to map a response surface that modeled the difference between mission success rates calculated for current health management technology and ISHM. Using representative data for a UAS, the analysis determined that the failure distribution parameters, sensor quality (which determines the relationship between probability of detection and probability of false alarm), and probability of an imminent fault during a mission were significant to the model. The result of the model determined that ISHM can result in a significant improvement on mission assurance, especially when implemented with higher quality sensors and on vehicles where the probability of imminent failure is higher relative to the mission times and time between preventative maintenance. This appears consistent with the premise that ISHM can support an extension of preventative maintenance intervals with an attendant reduction in sustainment cost

Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development

The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella, a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E. tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of EtAMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Socio-emotional problems in boys with sex chromosome aneuploidies compared to a clinical sample

Boys with sex chromosome aneuploidies (SCA) represent an understudied group. We examined parent-reported physical and socio-emotional problems in 25 boys with SCA (Mean age = 11.7 years, SD = 4.5). The majority had no severe physical health problems. One third of the sample had sleep problems and half of them had weekly or monthly pain. Total emotional and behavior problems, as assessed with the Strengths and Difficulties Questionnaire, were at the same level as reported for boys referred to child mental health clinics. Thus, boys with SCA may have the same need for psychological assessment and intervention as clinic-referred boys

Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007.

BACKGROUND: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. METHODS: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. RESULTS: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. CONCLUSIONS: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved

New structural systematics in the lanthanide elements at high pressure

The pressure-induced structural phase transitions in the lanthanide elements provide insight into changes in their electronic structures at high densities. After a series of transitions via close-packed structures, the regular trivalent lanthanides (La to Lu, excluding Ce, Eu and Yb) undergo first-order transitions to so-called collapsed phases, the structures of which have long been reported as monoclinic. However, the diffraction data from these phases are not well fitted by this monoclinic structure, and the patterns from Nd and Sm are distinctly different to those from the higher-Z lanthanides (Gd→). Here we present results from recent diffraction studies on Tb, Gd, Sm, Nd and Y to above 300 GPa, which reveal that there are two different collapsed structures, neither of which is monoclinic. High-precision equation of state studies of the same elements reveal distinct changes in compressibility once the collapsed phases are obtained. We also show that these new structures are strikingly similar to those observed in the higher-Z actinides at high pressure, greatly strengthening the structural systematics of the 4f and 5f elements