Visualizing the Topical Structure of the Medical Sciences: A Self-Organizing Map Approach

Background

We implement a high-resolution visualization of the medical knowledge domain using the self-organizing map (SOM) method, based on a corpus of over two million publications. While self-organizing maps have been used for document visualization for some time, (1) little is known about how to deal with truly large document collections in conjunction with a large number of SOM neurons, (2) post-training geometric and semiotic transformations of the SOM tend to be limited, and (3) no user studies have been conducted with domain experts to validate the utility and readability of the resulting visualizations. Our study makes key contributions to all of these issues.

Methodology

Documents extracted from Medline and Scopus are analyzed on the basis of indexer-assigned MeSH terms. Initial dimensionality is reduced to include only the top 10% most frequent terms and the resulting document vectors are then used to train a large SOM consisting of over 75,000 neurons. The resulting two-dimensional model of the high-dimensional input space is then transformed into a large-format map by using geographic information system (GIS) techniques and cartographic design principles. This map is then annotated and evaluated by ten experts stemming from the biomedical and other domains.

Conclusions

Study results demonstrate that it is possible to transform a very large document corpus into a map that is visually engaging and conceptually stimulating to subject experts from both inside and outside of the particular knowledge domain. The challenges of dealing with a truly large corpus come to the fore and require embracing parallelization and use of supercomputing resources to solve otherwise intractable computational tasks. Among the envisaged future efforts are the creation of a highly interactive interface and the elaboration of the notion of this map of medicine acting as a base map, onto which other knowledge artifacts could be overlaid.     

Associations between Extending Access to Primary Care and Emergency Department Visits: A Difference-In-Differences Analysis

BackgroundHealth services across the world increasingly face pressures on the use of expensive hospital services. Better organisation and delivery of primary care has the potential to manage demand and reduce costs for hospital services, but routine primary care services are not open during evenings and weekends.Extended access (evening and weekend opening) is hypothesized to reduce pressure on hospital services from emergency department visits. However, the existing evidence-base is weak, largely focused on emergency out-of-hours services, and analysed using a before-and after-methodology without effective comparators.ConclusionsThe study found that extending access was associated with a reduction in emergency department visits in the first 12 months. The results of the research have already informed the decision by National Health Service England to extend primary care access across Greater Manchester from 2016. However, further evidence is needed to understand whether extending primary care access is cost-effective and sustainable.     

Decoupled genomic elements and the evolution of partner quality in nitrogen‐fixing rhizobia

Understanding how mutualisms evolve in response to a changing environment will be critical for predicting the long‐term impacts of global changes, such as increased N (nitrogen) deposition. Bacterial mutualists in particular might evolve quickly, thanks to short generation times and the potential for independent evolution of plasmids through recombination and/or HGT (horizontal gene transfer). In a previous work using the legume/rhizobia mutualism, we demonstrated that long‐term nitrogen fertilization caused the evolution of less‐mutualistic rhizobia. Here, we use our 63 previously isolated rhizobium strains in comparative phylogenetic and quantitative genetic analyses to determine the degree to which variation in partner quality is attributable to phylogenetic relationships among strains versus recent genetic changes in response to N fertilization. We find evidence of distinct evolutionary relationships between chromosomal and pSym genes, and broad similarity between pSym genes. We also find that nifD has a unique evolutionary history that explains much of the variation in partner quality, and suggest MoFe subunit interaction sites in the evolution of less‐mutualistic rhizobia. These results provide insight into the mechanisms behind the evolutionary response of rhizobia to long‐term N fertilization, and we discuss the implications of our results for the evolution of the mutualism.     

Rescue of cytochrome P450 oxidoreductase (Por) mouse mutants reveals functions in vasculogenesis, brain and limb patterning linked to retinoic acid homeostasis

Cytochrome P450 oxidoreductase (POR) acts as an electron donor for all cytochrome P450 enzymes. Knockout mouse Por(-/-) mutants, which are early embryonic (E9.5) lethal, have been found to have overall elevated retinoic acid (RA) levels, leading to the idea that POR early developmental function is mainly linked to the activity of the CYP26 RA-metabolizing enzymes (Otto et al., Mol. Cell. Biol. 23, 6103-6116). By crossing Por mutants with a RA-reporter lacZ transgene, we show that Por(-/-) embryos exhibit both elevated and ectopic RA signaling activity e.g. in cephalic and caudal tissues. Two strategies were used to functionally demonstrate that decreasing retinoid levels can reverse Por(-/-) phenotypic defects, (i) by culturing Por(-/-) embryos in defined serum-free medium, and (ii) by generating compound mutants defective in RA synthesis due to haploinsufficiency of the retinaldehyde dehydrogenase 2 (Raldh2) gene. Both approaches clearly improved the Por(-/-) early phenotype, the latter allowing mutants to be recovered up until E13.5. Abnormal brain patterning, with posteriorization of hindbrain cell fates and defective mid- and forebrain development and vascular defects were rescued in E9.5 Por(-/-) embryos. E13.5 Por(-/-); Raldh2(+/-) embryos exhibited abdominal/caudal and limb defects that strikingly phenocopy those of Cyp26a1(-/-) and Cyp26b1(-/-) mutants, respectively. Por(-/-); Raldh2(+/-) limb buds were truncated and proximalized and the anterior-posterior patterning system was not established. Thus, POR function is indispensable for the proper regulation of RA levels and tissue distribution not only during early embryonic development but also in later morphogenesis and molecular patterning of the brain, abdominal/caudal region and limbs.     

Shedding and intracage transmission of Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus) model

The mechanism(s) by which Sin Nombre (SN) hantavirus is maintained in deer mouse populations is unclear. Field studies indicate that transmission occurs primarily if not exclusively via a horizontal mechanism. Using an experimental deer mouse infection model in an outdoor laboratory, we tested whether infected rodents shed SN virus in urine, feces, and saliva, whether infected mice transmit infection to na?ve cage mates, and whether infected dams are able to vertically transmit virus or antibody to offspring. Using pooled samples of urine, feces, and saliva collected from mice infected 8 to 120 days postinoculation (p.i.), we found that a subset of saliva samples, collected between 15 and 90 days p.i., contained viral RNA. Parallel studies conducted on wild-caught, naturally infected deer mice showed a similar pattern of intermittent positivity, also only in saliva samples. Attempts to isolate virus through inoculation of cells or na?ve deer mice with the secreta or excreta of infected mice were uniformly negative. Of 54 attempts to transmit infection by cohousing infected deer mice with seronegative cage mates, we observed only a single case of transmission, which occurred between 29 and 42 days p.i. Dams passively transferred antibodies to neonatal pups via milk, and those antibodies persisted for at least 2 months after weaning, but none transmitted infection to their pups. Compared to other hantavirus models, SN virus is shed less efficiently and transmits inefficiently among cage mates. Transmission of SN virus among reservoir rodents may require factors that are not required for other hantaviruses.