The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality

Background

The occurrence of variations in the spectrum of cardiovascular disease between different regions of the world and ethnic groups have been the subject of great interest. This study report the 24-h variation of myocardial infarction (MI) occurrence in patients recruited from CCU located in Argentina and Uruguay.

Methods

A cohort of 1063 patients admitted to the CCU within 24 h of the onset of symptoms of an acute MI was examined. MI incidence along the day was computed in 1 h-intervals.

Results

A minimal MI incidence between 03:00 and 07:00 h and the occurrence of a first maximum between 08:00 and 12:00 h and a second maximum between 15:00 and 22:00 h were verified. The best fit curve was a 24 h cosinor (acrophase ~ 19:00 h, accounting for 63 % of variance) together with a symmetrical gaussian bell (maximum at ~ 10:00 h, accounting for 37 % of variance). A similar picture was observed for MI frequencies among different excluding subgroups (older or younger than 70 years; with or without previous symptoms; diabetics or non diabetics; Q wave- or non-Q wave-type MI; anterior or inferior MI location). Proportion between cosinor and gaussian probabilities was maintained among most subgroups except for older patients who had more MI at the afternoon and patients with previous symptoms who were equally distributed among the morning and afternoon maxima.

Conclusion

The results support the existence of two maxima (at morning and afternoon hours) in MI incidence in the Argentine and Uruguayan population.     

Mainstreaming animal-assisted therapy

The term animal-assisted therapy (AAT) commonly refers to the presentation of an animal to one or more persons for the purpose of providing a beneficial impact on human health or well-being. AAT is an ideal example of "One Health" because of numerous studies and widespread testimonials indicating that many humans feel better in the presence of pets and other domesticated animals, and, conversely, that some of those creatures appear to respond positively to human company for their emotional and perhaps physical betterment. Many AAT studies have claimed a wide range of human health benefits, but much of the research is characterized by small-scale interventions among disparate fields, resulting in criticisms about weak study design or inconsistent methodology. Such criticisms contrast with the strongly held belief among many that interaction with friendly animals has a strong and innate value for the persons involved. Consequently the appeal of AAT in human medicine today may be generally characterized as a "push" by enthusiastic advocates rather than a "pull" by prescribing physicians. To fully integrate AAT into conventional medical practice as an accepted therapeutic modality, more convincing intervention studies are necessary to confirm its clinical merits, along with an understanding of the underlying mechanism of the human response to the company of friendly animals.     

Ranking non-synonymous single nucleotide polymorphisms based on disease concepts

As the number of non-synonymous single nucleotide polymorphisms (nsSNPs) identified through whole-exome/whole-genome sequencing programs increases, researchers and clinicians are becoming increasingly reliant upon computational prediction algorithms designed to prioritize potential functional variants for further study. A large proportion of existing prediction algorithms are ‘disease agnostic’ but are nevertheless quite capable of predicting when a mutation is likely to be deleterious. However, most clinical and research applications of these algorithms relate to specific diseases and would therefore benefit from an approach that discriminates between functional variants specifically related to that disease from those which are not. In a whole-exome/whole-genome sequencing context, such an approach could substantially reduce the number of false positive candidate mutations. Here, we test this postulate by incorporating a disease-specific weighting scheme into the Functional Analysis through Hidden Markov Models (FATHMM) algorithm. When compared to traditional prediction algorithms, we observed an overall reduction in the number of false positives identified using a disease-specific approach to functional prediction across 17 distinct disease concepts/categories. Our results illustrate the potential benefits of making disease-specific predictions when prioritizing candidate variants in relation to specific diseases. A web-based implementation of our algorithm is available at http://fathmm.biocompute.org.uk.     

Comparison of methods for determining the numbers and species distribution of coliform bacteria in well water samples

AIMS: Enumeration of coliform bacteria and Escherichia coli is the most widely used method in the estimation of hygienic quality of drinking water. The yield of target bacteria and the species composition of different populations of coliform bacteria may depend on the method.Three methods were compared. METHODS AND RESULTS: Three membrane filtration methods were used for the enumeration of coliform bacteria in shallow well waters. The yield of confirmed coliform bacteria was highest on Differential Coliform agar, followed by LES Endo agar. Differential Coliform agar had the highest proportion of typical colonies, of which 74% were confirmed as belonging to the Enterobacteriaceae. Of the typical colonies on Lactose Tergitol 7 TTC agar, 75% were confirmed as Enterobacteriaceae, whereas 92% of typical colonies on LES Endo agar belonged to the Enterobacteriaceae. LES Endo agar yielded many Serratia strains, Lactose Tergitol 7 TTC agar yielded numerous strains of Rahnella aquatilis and Enterobacter, whereas Differential Coliform agar yielded the widest range of species. CONCLUSION: The yield of coliform bacteria varied between methods. Each method compared had a characteristic species distribution of target bacteria and a typical level of interference of non-target bacteria. Identification with routine physiological tests to distinct species was hampered by the slight differences between species. High yield and sufficient selectivity are difficult to achieve simultaneously, especially if the target group is diverse. SIGNIFICANCE AND IMPACT OF THE STUDY: The results showed that several aspects of method performance should be considered, and that the target group must be distinctly defined to enable method comparisons.     

Mesoscale distribution and functional diversity of picoeukaryotes in the first-year sea ice of the Canadian Arctic

Sea ice, a characteristic feature of polar waters, is home to diverse microbial communities. Sea-ice picoeukaryotes (unicellular eukaryotes with cell size <3 μm) have received little attention compared with diatoms that dominate the spring bloom in Arctic first-year sea ice. Here, we investigated the abundance of all picoeukaryotes, and of 11 groups (chlorophytes, cryptophytes, bolidophytes, haptophytes, Pavlovaphyceae, Phaeocystis spp., pedinellales, stramenopiles groups MAST-1, MAST-2 and MAST-6 and Syndiniales Group II) at 13 first-year sea-ice stations localized in Barrow Strait and in the vicinity of Cornwallis Island, Canadian Arctic Archipelago. We applied Catalyzed Reporter Deposition–Fluorescence In Situ Hybridization to identify selected groups at a single cell level. Pavlovaphyceae and stramenopiles from groups MAST-2 and MAST-6 were for the first time reported from sea ice. Total numbers of picoeukaryotes were significantly higher in the vicinity of Cornwallis Island than in Barrow Strait. Similar trend was observed for all the groups except for haptophytes. Chlorophytes and cryptophytes were the dominant plastidic, and MAST-2 most numerous aplastidic of all the groups investigated. Numbers of total picoeukaryotes, chlorophytes and MAST-2 stramenopiles were positively correlated with the thickness of snow cover. All studied algal and MAST groups fed on bacteria. Presence of picoeukaryotes from various trophic groups (mixotrophs, phagotrophic and parasitic heterotrophs) indicates the diverse ecological roles picoeukaryotes have in sea ice. Yet, >50% of total sea-ice picoeukaryote cells remained unidentified, highlighting the need for further study of functional and phylogenetic sea-ice diversity, to elucidate the risks posed by ongoing Arctic changes.     

A simple approach to estimate similarity in ecosystem analysis

A simple rank similarity index is proposed to use in estimation of ecological community similarities. The analysis of similarities is based on hypergeometric probabilities of the coincidence of dominant species in the samples. When 4 dominant species are ranked in samples, two sets of ranks can be compared in 133 different ways. In the case of total similarity rank similarity index M=10 and for dissimilarity M=0. Critical levels of M are given for total amount of species from 10 to 300. The proposed approach useful in rapid similarity analysis of planktonic communities.     

A probability-based indicator of ecological condition

We introduce a new method for quantifying the ecological condition (C) of sites based on documented species’ responses to environmental stress. Preliminary research is needed to establish species-specific logistic functions, representing probabilities of finding individual species across an explicit reference gradient, ranging from maximally stressed (C = 0) to minimally stressed (C = 10) localities. Each function takes into account the species’ tolerance to stress, the species’ overall ubiquity, and the probability of detecting the species when it is present. Given a set of standardized species-specific functions, the ecological condition of any site can be derived by iteration, converging on the value of C that best “predicts” the species that are actually present. Species from multiple taxonomic groups can be included in the calculations, and results are not directly affected by species richness or sampling area. We demonstrate a successful application of this method for bird species assemblages in the U.S. portion of the Great Lakes coastal zone. Approximately, 28% of the bird species observed in the Eastern Deciduous Forest Ecological Province and 35% of the species in the Laurentian Mixed Forest Ecological Province showed strong relationships with a reference gradient of land cover variables. Functional stress–response relationships of these species can be used effectively to estimate ecological condition at new sites. The estimated condition based on bird species generally mirrors the reference condition, but deviations from the expected 1:1 relationship provide meaningful insights about ecological condition of the target areas. Sensitivity analysis using different numbers of species shows that our method is robust and can be applied consistently with 25–30 species exhibiting strong stress–response functions.     

Accelerated maximum likelihood parameter estimation for stochastic biochemical systems

ABSTRACT: BACKGROUND: A prerequisite for the mechanistic simulation of a biochemical system is detailed knowledge of its kinetic parameters. Despite recent experimental advances, the estimation of unknown parameter values from observed data is still a bottleneck for obtaining accurate simulation results. Many methods exist for parameter estimation in deterministic biochemical systems; methods for discrete stochastic systems are less well developed. Given the probabilistic nature of stochastic biochemical models, a natural approach is to choose parameter values that maximize the probability of the observed data with respect to the unknown parameters, a.k.a. the maximum likelihood parameter estimates (MLEs). MLE computation for all but the simplest models requires the simulation of many system trajectories that are consistent with experimental data. For models with unknown parameters, this presents a computational challenge, as the generation of consistent trajectories can be an extremely rare occurrence. RESULTS: We have developed Monte Carlo Expectation-Maximization with Modified Cross-Entropy Method (MCEM2): an accelerated method for calculating MLEs that combines advances in rare event simulation with a computationally efficient version of the Monte Carlo expectation-maximization (MCEM) algorithm. Our method requires no prior knowledge regarding parameter values, and it automatically provides a multivariate parameter uncertainty estimate. We applied the method to five stochastic systems of increasing complexity, progressing from an analytically tractable pure-birth model to a computationally demanding model of yeast-polarization. Our results demonstrate that MCEM2 substantially accelerates MLE computation on all tested models when compared to a stand-alone version of MCEM. Additionally, we show how our method identifies parameter values for certain classes of models more accurately than two recently proposed computationally efficient methods. CONCLUSIONS: This work provides a novel, accelerated version of a likelihood-based parameter estimation method that can be readily applied to stochastic biochemical systems. In addition, our results suggest opportunities for added efficiency improvements that will further enhance our ability to mechanistically simulate biological processes.     

Veratridine enhancement of agonist-induced synaptic membrane depolarization in electroplax.

Veratridine in low concentrations (20 μ$\text{M}$) and at high pH (pH 9) acts as a synergist for carbamylcholine-induced depolarizations in the electroplax of electric eel. This potentiation is not sensitive to tetrodotoxin, but is significantly reduced by d-tubocurarine. Veratridine alone does not depolarize this preparation at the concentration used (20 μ$\text{M}$). The increased carbamylcholine depolarization arising in the presence of veratridine does not simply sum with the carbamylcholine depolarization; the fractional contribution of veratridine to the total depolarization decreases as the carbamylcholine concentration is increased, and at 50 μM carbamylcholine no significant difference is apparent between groups with and without veratridine. Depolarization with increased external K⁺, unlike carbamylcholine depolarization, is not potentiated by veratridine.