Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts

Background

Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study.

Methods and Results

We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors.

Conclusions

We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM.     

Asynchrony between Host Plant and Insects-Defoliator within a Tritrophic System: The Role of Herbivore Innate Immunity

The effects of asynchrony in the phenology of spring-feeding insect-defoliators and their host plants on insects’ fitness, as well as the importance of this effect for the population dynamics of outbreaking species of insects, is a widespread and well-documented phenomenon. However, the spreading of this phenomenon through the food chain, and especially those mechanisms operating this spreading, are still unclear. In this paper, we study the effect of seasonally declined leafquality (estimated in terms of phenolics and nitrogen content) on herbivore fitness, immune parameters and resistance against pathogen by using the silver birch Betula pendula—gypsy moth Lymantria dispar—nucleopolyhedrovirus as the tritrophic system. We show that a phenological mismatch induced by the delay in the emergence of gypsy moth larvae and following feeding on mature leaves has negative effects on the female pupal weight, on the rate of larval development and on the activity of phenoloxidase in the plasma of haemolymph. In addition, the larval susceptibility to exogenous nucleopolyhydrovirus infection as well as covert virus activation were both enhanced due to the phenological mismatch. The observed effects of phenological mismatch on insect-baculovirus interaction may partially explain the strong and fast fluctuations in the population dynamics of the gypsy moth that is often observed in the studied part of the defoliator area. This study also reveals some indirect mechanisms of effect related to host plant quality, which operate through the insect innate immune status and affect resistance to both exogenous and endogenous virus.     

Using QTL mapping to investigate the relationships between abiotic stress tolerance (drought and salinity) and agronomic and physiological traits

Background

Drought and salinity are two major abiotic stresses that severely limit barley production worldwide. Physiological and genetic complexity of these tolerance traits has significantly slowed the progress of developing stress-tolerant cultivars. Marker-assisted selection (MAS) may potentially overcome this problem. In the current research, seventy two double haploid (DH) lines from a cross between TX9425 (a Chinese landrace variety with superior drought and salinity tolerance) and a sensitive variety, Franklin were used to identify quantitative trait loci (QTL) for drought and salinity tolerance, based on a range of developmental and physiological traits.

Results

Two QTL for drought tolerance (leaf wilting under drought stress) and one QTL for salinity tolerance (plant survival under salt stress) were identified from this population. The QTL on 2H for drought tolerance determined 42% of phenotypic variation, based on three independent experiments. This QTL was closely linked with a gene controlling ear emergency. The QTL on 5H for drought tolerance was less affected by agronomic traits and can be effectively used in breeding programs. A candidate gene for this QTL on 5H was identified based on the draft barley genome sequence. The QTL for proline accumulation, under both drought and salinity stresses, were located on different positions to those for drought and salinity tolerance, indicating no relationship with plant tolerance to either of these stresses.

Conclusions

Using QTL mapping, the relationships between QTL for agronomic and physiological traits and plant drought and salinity tolerance were studied. A new QTL for drought tolerance which was not linked to any of the studied traits was identified. This QTL can be effectively used in breeding programs. It was also shown that proline accumulation under stresses was not necessarily linked with drought or salinity tolerance based on methods of phenotyping used in this experiment. The use of proline content in breeding programs can also be limited by the accuracy of phenotyping.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1243-8) contains supplementary material, which is available to authorized users.     

Very stable high molecular mass multiprotein complex with DNase and amylase activities in human milk

For breastfed infants, human milk is more than a source of nutrients; it furnishes a wide array of proteins, peptides, antibodies, and other components promoting neonatal growth and protecting infants from viral and bacterial infection. It has been proposed that most biological processes are performed by protein complexes. Therefore, identification and characterization of human milk components including protein complexes is important for understanding the function of milk. Using gel filtration, we have purified a stable high molecular mass (~1000 kDa) multiprotein complex (SPC) from 15 preparations of human milk. Light scattering and gel filtration showed that the SPC was stable in the presence of high concentrations of NaCl and MgCl₂ but dissociated efficiently under the conditions that destroy immunocomplexes (2 M MgCl₂, 0.5 M NaCl, and 10 mM DTT). Such a stable complex is unlikely to be a casual associate of different proteins. The relative content of the individual SPCs varied from 6% to 25% of the total milk protein. According to electrophoretic and mass spectrometry analysis, all 15 SPCs contained lactoferrin (LF) and α‐lactalbumin as major proteins, whereas human milk albumin and β‐casein were present in moderate or minor amounts; a different content of IgGs and sIgAs was observed. All SPCs efficiently hydrolyzed Plasmid supercoiled DNA and maltoheptaose. Some freshly prepared SPC preparations contained not only intact LF but also small amounts of its fragments, which appeared in all SPCs during their prolonged storage; the fragments, similar to intact LF, possessed DNase and amylase activities. LF is found in human epithelial secretions, barrier body fluids, and in the secondary granules of leukocytes. LF is a protein of the acute phase response and nonspecific defense against different types of microbial and viral infections. Therefore, LF complexes with other proteins may be important for its functions not only in human milk. Copyright © 2014 John Wiley & Sons, Ltd.     

Collective action problem in heterogeneous groups

I review the theoretical and experimental literature on the collective action problem in groups whose members differ in various characteristics affecting individual costs, benefits and preferences in collective actions. I focus on evolutionary models that predict how individual efforts and fitnesses, group efforts and the amount of produced collective goods depend on the group''s size and heterogeneity, as well as on the benefit and cost functions and parameters. I consider collective actions that aim to overcome the challenges from nature or win competition with neighbouring groups of co-specifics. I show that the largest contributors towards production of collective goods will typically be group members with the highest stake in it or for whom the effort is least costly, or those who have the largest capability or initial endowment. Under some conditions, such group members end up with smaller net pay-offs than the rest of the group. That is, they effectively behave as altruists. With weak nonlinearity in benefit and cost functions, the group effort typically decreases with group size and increases with within-group heterogeneity. With strong nonlinearity in benefit and cost functions, these patterns are reversed. I discuss the implications of theoretical results for animal behaviour, human origins and psychology.     

Population genomic analysis uncovers African and European admixture in Drosophila melanogaster populations from the south‐eastern United States and Caribbean Islands

Drosophila melanogaster is postulated to have colonized North America in the past several 100 years in two waves. Flies from Europe colonized the east coast United States while flies from Africa inhabited the Caribbean, which if true, make the south‐east US and Caribbean Islands a secondary contact zone for African and European D. melanogaster. This scenario has been proposed based on phenotypes and limited genetic data. In our study, we have sequenced individual whole genomes of flies from populations in the south‐east US and Caribbean Islands and examined these populations in conjunction with population sequences from the west coast US, Africa, and Europe. We find that west coast US populations are closely related to the European population, likely reflecting a rapid westward expansion upon first settlements into North America. We also find genomic evidence of African and European admixture in south‐east US and Caribbean populations, with a clinal pattern of decreasing proportions of African ancestry with higher latitude. Our genomic analysis of D. melanogaster populations from the south‐east US and Caribbean Islands provides more evidence for the Caribbean Islands as the source of previously reported novel African alleles found in other east coast US populations. We also find the border between the south‐east US and the Caribbean island to be the admixture hot zone where distinctly African‐like Caribbean flies become genomically more similar to European‐like south‐east US flies. Our findings have important implications for previous studies examining the generation of east coast US clines via selection.     

Psychometric properties of the Russian version of the Composite Scale of Morningness

Morningness–eveningness preference is commonly measured by questionnaires, such as the Composite Scale of Morningness (CSM). Purpose of our study was to assess the Russian translation of the CSM and provide psychometric properties of this scale. Participants (N = 406) were students from high schools and university in Petrozavodsk. Mean age was 20.47 ± 3.66 with a range of 12–38 years. Mean CSM scores were 31.43 ± 6.32, with a range from 14 to 50. Internal reliability, as measured by Cronbach’s α, was 0.823. There was no negative correlation among the items. The reliability of 0.82 is good and fits into previous work done with the CSM in many different countries. The factor structure appears as a two-factor structure based on parallel analysis and a three-factor structure based on the eigenvalue greater than one criterion. We suggest retaining the two-factor structure, one factor could be labelled as morning affect and the other one as self-assessment/activity planning. Construct validity was checked with the MCTQ and showed that the correlations between midpoint of sleep and CSM are comparable to other studies.     

Heteromerous Bistricyclic Aromatic Enes: Dynamic Stereochemistry of Xanthylidene‐Anthrones

The heteromerous bistricyclic aromatic ene (BAE) 2,2'‐dimethyl‐10‐(9H‐xanthylidene)‐9(10H)‐anthrone (DMXA) was synthesized by a condensation of 10,10‐dichloro‐2‐methylxanthene with 2‐methylanthrone. X‐ray crystallography of (E)‐DMXA and xanthylidene‐anthrone (XA) indicated that the molecules adopt anti‐folded conformations with folding dihedral angles of 44°/44° and 39°/41°, respectively . The crystal structure of anti‐folded (E)‐DMXA does not indicate any xanthenylium–anthracenolate push–pull effect. E,Z‐diastereomerization of DMXA was studied by ¹H‐NMR coalescence‐temperature measurements at different magnetic field strengths and by kinetic equilibration experiments . Free energy of activation for this process was 81.5 (±1.3) kJ/mol. B3LYP/6‐311+G(d,p) calculations showed that anti‐folded conformers of XA, (E)‐DMXA, bianthrone (AA), and dixanthylene (XX) were global minima. The twisted conformers of XA, AA, and XX were local minima (ΔG₂₉₈ = 16, 18, and 24 kJ/mol) with a substantial dipolar xanthenylium–anthracenolate dipolar contribution for XA. Chirality 27:919–928, 2015. © 2015 Wiley Periodicals, Inc.