Focus: A Multifaceted Battle Against Cancer: Extracting Knowledge from Chemical Imaging Data Using Computational Algorithms for Digital Cancer Diagnosis

Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer.     

Functional classifications of coastal barrier island vegetation

Abstract. Due to the complexity of coastal barrier vegetation, it is useful to apply a functional-type approach to assess the response of barrier island vegetation to climate change. In this paper, a simple clustering analysis is applied to a group of 19 plant associations, based on six plant attributes and six environmental constraints. This analysis results in the suggestion that the main division of the vegetation types at Virginia Coast Reserve is between herbaceous and woody types, which differs from the existing classification which recognizes three groups: xeric-mesic herbaceous, woody and hydric-halophytic herbaceous. Considerations about grouping plant functional types are also addressed in this paper. At a global scale, inclusion of barrier plant functional types may not be so important for the climate-change response of vegetation, but it may be necessary to consider these important systems for spatially explicit modelling of landscape responses.     

Are research efforts on Animalia in the South Pacific associated with the conservation status or population trends?

Analyses of knowledge gaps can highlight imbalances in research, encouraging greater proportionality in the distribution of research efforts. In this research we used generalized linear mixed models (GLMM) with the aim to determine if research efforts for the period 2005–2015 for terrestrial vertebrates of Amphibia, Aves, Mammalia and Reptilia in the South Pacific region were correlated with conservation status (critically endangered (CR), endangered (EN), vulnerable (VU), least concern (LC) and near threatened (NT)) or population trends (increasing, stable, decreasing and unknown) through the International Union for Conservation of Nature (IUCN) database. Our results showed that research distribution was uneven across different classes. Out of 633623 investigated papers, the average number of publications per species was 43.7, 306.7, 717.6 and 115.3 for Amphibia (284 species), Aves (1306 species), Mammalia (243 species) and Reptilia (400 species), respectively. Consistently, the lower publication effort on Amphibia compared to other taxonomic classes was revealed as significant by GLMM analysis. There was no significant differences in research effort among levels of conservation status. However, we found significantly different publication efforts among population trends of all examined species in that species with “unknown” population trends gained significantly lower researchers’ attention compared to species with “decreasing” trend. Results also indicated that, although it was not significant, the highest attention is given to species with “increasing” population trend over all taxonomic classes. Using the Information Theoretic approach we also generated a set of competing models to identify most important factors influencing research efforts, revealing that the highest ranked model included taxonomic class and population trend.     

EMAP-Wetlands: A sampling design with global application

The U.S. Environmental Protection Agency (EPA) initiated the Environmental Monitoring and Assessment Program (EMAP) in 1988. The wetland component (EMAP-Wetlands) is designed to provide quantitative assessments of the current status and long-term trends in the ecological condition of wetland resources. EMAP-Wetlands will develop a wetland monitoring network and will identify and evaluate indicators that describe and quantify wetland condition. The EMAP-Wetlands network will represent a probability sample of the total wetland resource. The EMAP sample is based on a triangular grid of approximately 12,600 sample points in the conterminous U.S. The triangular grid adequately samples wetland resources that are common and uniformly distributed in a region, such as the prairie pothole wetlands of the Midwest. However, the design is flexible and allows the base grid density to be increased to adequately sample wetland resources, such as the coastal wetlands of the Gulf of Mexico, which are distributed linearly along the coast. The Gulf sample network required a 49-fold increase in base grid density. EMAP-Wetlands aggregates the 56 U.S. Fish and Wildlife Service's (FWS) National Wetland Inventory (NWI) categories (Cowardin et al. 1979) into 12 functionally similar groups (Leibowitz et al. 1991). Both the EMAP sample design and aggregated wetland classes are suitable for global inventory and assessment of wetlands.The research described in this report has been funded by the U.S. Environmental Protection Agency. This document has been prepared at the EPA Environmental Research Laboratory in Corvallis, OR, through contract No. 68-C8-0006 to Man Tech Environmental Technology, Inc. This paper has been subjected to the Agency's peer and administrative review and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.     

The Effects of Misspecification of a Regression Model

The consequences of the misspecification of a regression model are considered. For small effects of covariates a proportional consistency theorem is derived. The consistent estimation of the covariance matrix of the estimates is discussed.     

Analysis of Profiles Based on Ordinal Classification Functions and Rank Tests

In this article a test for the comparison of K groups of independent profiles is suggested. It is based on rank tests, in which the criterion is obtained by using a suitably chosen ordinal classification function. This function represents a specific view on the profiles. The test, which is easy to use, can be regarded as a generalisation of other well known tests and can be applied within a variety of situations. The relationships to other procedures for the analysis of profiles are described. Some properties are discussed.     

Novel summary metrics for insular biotic assemblages based on taxonomy and phylogeny: Biogeographical,palaeogeographical and possible conservational applications

Using the land‐bound vertebrates on the marine islands as model organisms, two metrics are presented that permit quantitative and succinct synopses of the ‘evolutionary maturity’ of the hosted faunal assemblages. In turn, these reflect the geo‐physical settings and geological developments of the substrates. The assemblage lineage‐taxonomy spectrum (ALTS) is based on the constituent lineages’ taxonomic distinctiveness and diversity. Individual lineages within assemblages can in most cases be assigned to one of six categories, LT1?LT6: LT1 is a non‐endemic taxon, whereas LT6 comprises multiple endemic genera from a family that arose elsewhere. If required, the scheme can be expanded: LT9 is an endemic order. The data can then be combined to provide an assemblage spectrum, for example, 00:08:38:30:08:15[ 13 ]. Here, the first six values denote the number of lineages assigned to each category expressed as percentages of the overall total, with the sum of the processed lineages listed as the seventh (in brackets and bold). The ALTS metric highlights efficiently the key features of a marine island's biological assemblage. Notably, the contrast between spectra for suites on geologically and geo‐physically varied island types can be striking, for instance the squamate suite on the young, proximate orogenic margin island of Taiwan is coded 78:16:05:00:00:00[ 37 ] whereas the one on the distantly located, Late Eocene composite terrane island of New Caledonia is 00:11:00:11:33:44[ 9 ]. To overcome the subjectivity that is inherent in assigning supraspecific ranks, an alternative assemblage lineage‐age spectrum (ALAS) is also introduced that makes use of the binary logarithm values of the colonization times of the island lineages (0–2, 2–4, … , 32–64, >64 Ma). It is represented using a seven‐plus‐two‐number code, for instance Madagascar's squamates are 00:06:00:00:19:62:12[ 19 ( 16 )]; most colonizations took place in the Palaeogene (66–23 Ma); there are 19 lineages, but only 16 are presently age‐dated. In addition to marine‐island biogeography studies, the ALTS–ALAS spectrum approach is potentially useful for encapsulating biotas in other sorts of insular setting (e.g. lakes, mountain tops), and for evaluating palaeogeographical models. Furthermore, it may help emphasize the conservation value of an island's faunal assemblage.     

Typologie des rivières oligotrophes du massif Ardennais (Belgique) par l'analyse multivariée de relevés de diatomées benthiques

Typology of oligotrophic streams of the Ardenne (Belgium) by multivariate analysis of benthic diatoms records.During three years, samples of water and algae has been taken in 72 stations distributed on the river system of the northern part of the Ardennes. 357 taxa of diatoms have been identified. Principal component analysis and cluster analysis, applied to diatoms counts, allowed to classify the records in a table comparable to phytosociological tables. A continuum in the data is an indication of the progressive modification of the communities according to the physico-chemical characteristics of the water. Ten diatoms assemblages have been described and this typology has been compared to some algal associations defined in the literature. In natural environments, these 10 assemblages are strictly correlated with the nature of the geological substrate and the physico-chemical characteristics of the water. The sensibility of the oligotrophic streams is revealed by the speedy changes in the communities after following a small modification of the environmental factors (seasonal variations or light eutrophication).

---

Typologie des rivières oligotrophes du massif Ardennais (Belgique) par l'analyse multivariée de relevés de diatomées benthiques

     

Reactivity and binding of benzo(a)pyrene diol epoxide to poly(dG-dC).(dG-dC) and poly(dG-m5dC).(dG-m5dC) in the B and Z forms

The physical and covalent binding of the carcinogen benzo(a)pyrene-7,8-diol-9,10-oxide (BaPDE) to poly(dG-dC).(dG-dC) and poly(dG-m5dC).(dG-m5dC) in the B and Z forms were studied utilizing absorbance, fluorescence and linear dichroism techniques. In the case of poly(dG-dC).(dG-dC) the decrease in the covalent binding of BaPDE with increasing NaCl concentration (0.1-4 M) as the B form is transformed to the Z form is attributed to the effects of high ionic strengths on the reactivity and physical binding of BaPDE to the polynucleotides; these effects tend to obscure differences in reactivities with the B and Z forms of the nucleic acids. In the case of poly(dG-m5dC).(dG-m5dC) the B-to-Z transition is induced at low ionic strength (2 mM NaCl + 10 microM Co(NH3)6Cl3) and the covalent binding is found to be 2-3-times lower to the Z form than to the B form. Physical binding of BaPDE by intercalation, which precedes the covalent binding reaction, is significantly lower in the Z form than in the B form, thus accounting, in part, for the lower covalent binding. The linear dichroism characteristics of BaPDE covalently bound to the Z and B forms of poly(dG-m5dC).(dG-m5dC) are consistent with nonintercalative, probably external conformations of the aromatic pyrenyl residues.     

Murine splenocyte proliferation by porin of Shigella dysenteriae type 1 and inhibition of bacterial invasion of HeLa cell by anti-porin antibody

Abstract A highly sensitive nested polymerase chain reaction method was designed for the detection of a wide spectrum of strains from Borrelia burgdorferi sensu lato. This technique allows the detection of as little as 3 fg of total genomic DNA extracted and purified from pure cultures of the organism, this amount corresponds to less than 10 organisms. Two sets of primers homologous to conserved spots in the coding region of the hbb gene, encoding a conserved histone-like protein, were constructed. These were based on a multiple sequence alignment of 39 strains representing all the genomic groups described in B. burgdorferi sensu lato.