Bats host major mammalian paramyxoviruses

The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data

Niche as a determinant of word fate in online groups

Patterns of word use both reflect and influence a myriad of human activities and interactions. Like other entities that are reproduced and evolve, words rise or decline depending upon a complex interplay between {their intrinsic properties and the environments in which they function}. Using Internet discussion communities as model systems, we define the concept of a word niche as the relationship between the word and the characteristic features of the environments in which it is used. We develop a method to quantify two important aspects of the size of the word niche: the range of individuals using the word and the range of topics it is used to discuss. Controlling for word frequency, we show that these aspects of the word niche are strong determinants of changes in word frequency. Previous studies have already indicated that word frequency itself is a correlate of word success at historical time scales. Our analysis of changes in word frequencies over time reveals that the relative sizes of word niches are far more important than word frequencies in the dynamics of the entire vocabulary at shorter time scales, as the language adapts to new concepts and social groupings. We also distinguish endogenous versus exogenous factors as additional contributors to the fates of words, and demonstrate the force of this distinction in the rise of novel words. Our results indicate that short-term nonstationarity in word statistics is strongly driven by individual proclivities, including inclinations to provide novel information and to project a distinctive social identity.Comment: Supporting Information is available here: http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00

The decoupled nature of basal metabolic rate and body temperature in endotherm evolution

The origins of endothermy in birds and mammals are important events in vertebrate evolution. Endotherms can maintain their body temperature (Tb) over a wide range of ambient temperatures primarily using the heat that is generated continuously by their high basal metabolic rate (BMR)1. There is also an important positive feedback loop as Tb influences BMR1,2,3. Owing to this interplay between BMRs and Tb, many ecologists and evolutionary physiologists posit that the evolution of BMR and Tb must have been coupled during the radiation of endotherms3,4,5, changing with similar trends6,7,8. However, colder historical environments might have imposed strong selective pressures on BMR to compensate for increased rates of heat loss and to keep Tb constant9,10,11,12. Thus, adaptation to cold ambient temperatures through increases in BMR could have decoupled BMR from Tb and caused different evolutionary routes to the modern diversity in these traits. Here we show that BMR and Tb were decoupled in approximately 90% of mammalian phylogenetic branches and 36% of avian phylogenetic branches. Mammalian BMRs evolved with rapid bursts but without a long-term directional trend, whereas Tb evolved mostly at a constant rate and towards colder bodies from a warmer-bodied common ancestor. Avian BMRs evolved predominantly at a constant rate and without a long-term directional trend, whereas Tb evolved with much greater rate heterogeneity and with adaptive evolution towards colder bodies. Furthermore, rapid shifts that lead to both increases and decreases in BMRs were linked to abrupt changes towards colder ambient temperatures—although only in mammals. Our results suggest that natural selection effectively exploited the diversity in mammalian BMRs under diverse, often-adverse historical thermal environments

The unrecognised cost of cancer patients' unrelieved symptoms:a nationwide follow-up of their surviving partners

We investigated if a cancer patient's unrelieved symptoms during the last 3 months of life increase the risk of long-term psychological morbidity of the surviving partner. All women (n=506) living in Sweden under 80 years of age, who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were asked to answer an anonymous postal questionnaire, 2–4 years after their loss. The widows' psychological morbidity was associated with the patient's unrelieved mental symptoms. When the patient was perceived to have been very anxious during last three months of life (compared to no observed symptoms) the relative risks for the widows' psychological morbidity were: 2.5 (1.4–4.3) for depression and 3.4 (1.4–8.2) for anxiety. When comparing reports of the patient's pain (much vs no), the relative risks were 0.8 (0.5–1.2) for widowhood depression, and 0.8 (0.4–1.7) for widowhood anxiety. The patients were found to have had adequate access to physical pain control but poor access to psychological symptom control. Efficiency in diagnosing and treating psychological complications of terminally ill cancer patients may not only improve their quality of life but possibly also prevent long-term psychological morbidity of their surviving partners

On the origin of spaces: morphometric foundations of urban form evolution

The modern discipline of urban morphology gives us a ground for the comparative analysis of cities, which increasingly includes specific quantitative elements. In this paper, we make a further step forward towards the definition of a general method for the classification of urban form. We draw from morphometrics and taxonomy in life sciences to propose such method, which we name ‘urban morphometrics’. We then test it on a unit of the urban landscape named ‘Sanctuary Area’ (SA), explored in 45 cities whose origins span four historic time periods: Historic (medieval), Industrial (19th century), New Towns (post-WWII, high-rise) and Sprawl (post-WWII, low-rise). We describe each SA through 207 physical dimensions and then use these to discover features that discriminate them among the four temporal groups. Nine dimensions emerge as sufficient to correctly classify 90% of the urban settings by their historic origins. These nine attributes largely identify an area's ‘visible identity’ as reflected by three characteristics: (1) block perimeterness, or the way buildings define the street-edge; (2) building coverage, or the way buildings cover the land and (3) regular plot coverage, or the extent to which blocks are made of plots that have main access from a street. Hierarchical cluster analysis utilising only the nine key variables nearly perfectly clusters each SA according to its historic origin; moreover, the resulting dendrogram shows, just after WWII, the first ‘bifurcation’ of urban history, with the emergence of the modern city as a new ‘species’ of urban form. With ‘urban morphometrics’ we hope to extend urban morphological research and contribute to understanding the way cities evolve

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

BACKGROUND: Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. OBJECTIVES: The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. METHODS: We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. RESULTS: When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five patients exhibited a significant difference (p < 0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). CONCLUSIONS: The developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40264-014-0145-z) contains supplementary material, which is available to authorised users

Long-term follow-up and treatment of congenital alveolar proteinosis

<p>Abstract</p> <p>Background</p> <p>Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.</p> <p>Case presentation</p> <p>A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.</p> <p>Conclusions</p> <p>The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.</p

HIPPIE: Integrating Protein Interaction Networks with Experiment Based Quality Scores

Protein function is often modulated by protein-protein interactions (PPIs) and therefore defining the partners of a protein helps to understand its activity. PPIs can be detected through different experimental approaches and are collected in several expert curated databases. These databases are used by researchers interested in examining detailed information on particular proteins. In many analyses the reliability of the characterization of the interactions becomes important and it might be necessary to select sets of PPIs of different confidence levels. To this goal, we generated HIPPIE (Human Integrated Protein-Protein Interaction rEference), a human PPI dataset with a normalized scoring scheme that integrates multiple experimental PPI datasets. HIPPIE's scoring scheme has been optimized by human experts and a computer algorithm to reflect the amount and quality of evidence for a given PPI and we show that these scores correlate to the quality of the experimental characterization. The HIPPIE web tool (available at http://cbdm.mdc-berlin.de/tools/hippie) allows researchers to do network analyses focused on likely true PPI sets by generating subnetworks around proteins of interest at a specified confidence level

Gas flows, star formation and galaxy evolution

In the first part of this article we show how observations of the chemical evolution of the Galaxy: G- and K-dwarf numbers as functions of metallicity, and abundances of the light elements, D, Li, Be and B, in both stars and the interstellar medium (ISM), lead to the conclusion that metal poor HI gas has been accreting to the Galactic disc during the whole of its lifetime, and is accreting today at a measurable rate, ~2 Msun per year across the full disc. Estimates of the local star formation rate (SFR) using methods based on stellar activity, support this picture. The best fits to all these data are for models where the accretion rate is constant, or slowly rising with epoch. We explain here how this conclusion, for a galaxy in a small bound group, is not in conflict with graphs such as the Madau plot, which show that the universal SFR has declined steadily from z=1 to the present day. We also show that a model in which disc galaxies in general evolve by accreting major clouds of low metallicity gas from their surroundings can explain many observations, notably that the SFR for whole galaxies tends to show obvious variability, and fractionally more for early than for late types, and yields lower dark to baryonic matter ratios for large disc galaxies than for dwarfs. In the second part of the article we use NGC 1530 as a template object, showing from Fabry-Perot observations of its Halpha emission how strong shear in this strongly barred galaxy acts to inhibit star formation, while compression acts to stimulate it.Comment: 20 pages, 10 figures, to be presented at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Africa, proceedings published by Kluwer, Eds. D.L. Block, K.C. Freeman, I. Puerari, & R. Groes