Text-derived concept profiles support assessment of DNA microarray data for acute myeloid leukemia and for androgen receptor stimulation

Background  

High-throughput experiments, such as with DNA microarrays, typically result in hundreds of genes potentially relevant to the process under study, rendering the interpretation of these experiments problematic. Here, we propose and evaluate an approach to find functional associations between large numbers of genes and other biomedical concepts from free-text literature. For each gene, a profile of related concepts is constructed that summarizes the context in which the gene is mentioned in literature. We assign a weight to each concept in the profile based on a likelihood ratio measure. Gene concept profiles can then be clustered to find related genes and other concepts.     

Reviewing Biosphere Reserves globally: effective conservation action or bureaucratic label?

The Biosphere Reserve (BR) model of UNESCO's Man and the Biosphere Programme reflects a shift towards more accountable conservation. Biosphere Reserves attempt to reconcile environmental protection with sustainable development; they explicitly acknowledge humans, and human interests in the conservation landscape while still maintaining the ecological values of existing protected areas. Conceptually, this model is attractive, with 610 sites currently designated globally. Yet the practical reality of implementing dual ‘conservation’ and ‘development’ goals is challenging, with few examples successfully conforming to the model's full criteria. Here, we review the history of Biosphere Reserves from first inception in 1974 to the current status quo, and examine the suitability of the designation as an effective conservation model. We track the spatial expansion of Biosphere Reserves globally, assessing the influence of the Statutory Framework of the World Network of Biosphere Reserves and Seville strategy in 1995, when the BR concept refocused its core objectives on sustainable development. We use a comprehensive range of case studies to discuss conformity to the Programme, the social and ecological consequences associated with implementation of the designation, and challenges in aligning conservation and development. Given that the ‘Biosphere Reserve’ label is a relatively unknown designation in the public arena, this review also provides details on popularising the Biosphere Reserve brand, as well as prospects for further research, currently unexploited, but implicit in the designation.     

Geographic sampling bias in the South African Frog Atlas Project: implications for conservation planning

Quality conservation planning requires quality input data. However, the broad scale sampling strategies typically employed to obtain primary species distribution data are prone to geographic bias in the form of errors of omission. This study provides a quantitative measure of sampling bias to inform accuracy assessment of conservation plans based on the South African Frog Atlas Project. Significantly higher sampling intensity near to cities and roads is likely to result in overstated conservation priority and heightened conservation conflicts in urban areas. Particularly well sampled protected areas will also erroneously appear to contribute highly to amphibian biodiversity targets. Conversely, targeted sampling in the arid northwest and along mountain ranges is needed to ensure that these under-sampled regions are not excluded from conservation plans. The South African Frog Atlas Project offers a reasonably accurate picture of the broad scale west-to-east increase in amphibian richness and abundance, but geographic bias may limit its applicability for fine scale conservation planning. The Global Amphibian Assessment species distribution data offered a less biased alternative, but only at the cost of inflated commission error.     

Sociosexuality as predictor of sexual harassment and coercion in female and male high school students

Sexual harassment and coercion have mainly been considered from a sex difference perspective. While traditional social science theories have explained harassment as male dominance of females, the evolutionary perspective has suggested that sex differences in the desire for sex are a better explanation. This study attempts to address individual differences associated with harassment from an evolutionary perspective. Considering previous research that has found links between sociosexual orientation inventory (SOI) and harassment, we consider whether this association can be replicated in a large, representative sample of high school students (N=1199) from a highly egalitarian culture. Expanding the previous studies which mainly focused on male perpetrators and female victims, we also examine females and males as both perpetrators and as victims. We believe that unrestricted sociosexuality motivates people to test whether others are interested in short-term sexual relations in ways that sometimes might be defined as harassment. Furthermore, unrestricted individuals signal their sociosexual orientation, and while they do not desire all individuals that react to these signals with sexual advances, they attract much more sexual advances than individuals with restricted sociosexual orientations, especially from other unrestricted members of the opposite sex. This more or less unconscious signaling thus makes them exploitable, i.e., harassable. We find that SOI is a predictor for sexual harassment and coercion among high school students. The paper concludes that, as expected, unrestricted sociosexuality predicts being both a perpetrator and a victim of both same-sex and opposite-sex harassment.     

Specific IgA and metalloproteinase activity in bronchial secretions from stable chronic obstructive pulmonary disease patients colonized by Haemophilus influenzae

Background

Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.

Methods

A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed. Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples. Levels in patients colonized by H. influenzae and non-colonized patients were compared.

Results

Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test). Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test). Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).

Conclusions

Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients. Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases.     

A review of exotic animal disease in Great Britain and in Scotland specifically between 1938 and 2007

Background

Incursions of contagious diseases of livestock into disease-free zones are inevitable as long as the diseases persist elsewhere in the world. Knowledge of where, when and how incursions have occurred helps assess the risks, and regionalize preventative and reactive measures.

Methodology

Based on reports of British governmental veterinary services, we review occurrence of the former OIE List A diseases, and of Aujeszky''s disease, anthrax and bovine tuberculosis (bTB) in farm-animals in Great Britain (GB) between 1938 and 2007. We estimate incidence of each disease on GB agricultural holdings and fraction of susceptible farm-animals culled to control the disease each year. We then consider the frequency and incidence of the diseases in Scotland alone. The limitations of available data on historical disease occurrence and denominator populations are detailed in Text S2.

Conclusions

The numbers of livestock and poultry farmed in GB grew over the years 1938–2007; the number of agricultural holdings decreased. An amalgamation of production on larger holdings took place from the 1940s to the 1980s. The maximum annual incidence of a reviewed disease in GB 1938–2007 was reported for bTB, 1.69% of holdings in 1961. This was followed by Newcastle disease, 1.50% of holdings in 1971, and classical swine fever, 1.09% of holdings in 1940. The largest fractional cull of susceptible livestock in a single year in each of the four decades 1950s–1980s was due to a viral disease primarily affecting swine. During the periods 1938–1949 and 2000–2007 this was due to outbreaks of foot and mouth disease. In the absence of incursions of the former OIE List A diseases in the 1990s, this was due to bTB. Over the 70 years, the diseases were reported with lower frequency and lower annual incidence in Scotland, as compared to when these statistics are considered for GB as a whole.     

Peptide vaccine candidates against classical swine fever virus: T cell and neutralizing antibody responses of dendrimers displaying E2 and NS2–3 epitopes

Three peptide‐based systems integrating B and T antigenic sites of CSFV and displaying the B epitopes in fourfold presentation have been designed and produced, and shown to bring about significant enhancements in immunogenicity over the peptides in monomeric form. Of the different strategies tested for producing the dendrimeric constructs, stepwise SPPS using 3,6‐dioxaoctanoic acid as flexible, PEG‐like spacer units at the branching points is clearly advantageous, in particular over ligation in solution. The constructs have been used for immunization of domestic pigs, in order to evaluate the protective response induced by each peptide constructs, and to characterize the B‐ and T‐cell response against CSFV in the natural host. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Effectiveness of a Supportive Telephone Counseling Intervention in Type 2 Diabetes Patients: Randomized Controlled Study

Objectives

This randomized controlled trial investigated whether a patient-centered supportive counseling intervention comprising monthly telephone-based counseling sessions by practice nurses over 12 months improved diabetes-related medical and psycho-social outcomes above usual care in type 2 diabetes patients with poor glycemic control at baseline (HbA_1c >7.5%) in a primary care setting.

Research Design

Patients were individually randomized into intervention (n = 103) and usual care group (n = 101). The primary outcome was change in HbA_1c-concentration after 12 and 18 months. Secondary outcomes were lipid levels, blood pressure, health-related quality of life and symptoms of depression. Follow-up-measurements were carried out after 6, 12 and 18 months to assess potential immediate and maintained effects of the intervention. For the multivariate analysis, hierarchical linear models were computed for each outcome to assess within-group changes in outcomes over time and between-group differences in patterns of change.

Results

HbA_1c (in %) decreased significantly from baseline to 12-month follow-up measurement both in the intervention (−0.44) and the usual care group (−0.51), but there was no significant between-group intervention effect. Significant improvements in the intervention group along with significant between-group differences were seen for health-related quality of life and, transiently, for systolic blood pressure and depression.

Conclusions

Although we found no beneficial effect of the supportive telephone counseling in terms of a reduction of HbA_1c above usual care, our findings suggest some beneficial effects on cardiovascular risk factors, quality of life and depression. Continuous efforts might be needed to sustain improvements in patient outcomes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00742547","term_id":"NCT00742547"}}NCT00742547     

Generic Information Can Retrieve Known Biological Associations: Implications for Biomedical Knowledge Discovery

Motivation

Weighted semantic networks built from text-mined literature can be used to retrieve known protein-protein or gene-disease associations, and have been shown to anticipate associations years before they are explicitly stated in the literature. Our text-mining system recognizes over 640,000 biomedical concepts: some are specific (i.e., names of genes or proteins) others generic (e.g., ‘Homo sapiens’). Generic concepts may play important roles in automated information retrieval, extraction, and inference but may also result in concept overload and confound retrieval and reasoning with low-relevance or even spurious links. Here, we attempted to optimize the retrieval performance for protein-protein interactions (PPI) by filtering generic concepts (node filtering) or links to generic concepts (edge filtering) from a weighted semantic network. First, we defined metrics based on network properties that quantify the specificity of concepts. Then using these metrics, we systematically filtered generic information from the network while monitoring retrieval performance of known protein-protein interactions. We also systematically filtered specific information from the network (inverse filtering), and assessed the retrieval performance of networks composed of generic information alone.

Results

Filtering generic or specific information induced a two-phase response in retrieval performance: initially the effects of filtering were minimal but beyond a critical threshold network performance suddenly drops. Contrary to expectations, networks composed exclusively of generic information demonstrated retrieval performance comparable to unfiltered networks that also contain specific concepts. Furthermore, an analysis using individual generic concepts demonstrated that they can effectively support the retrieval of known protein-protein interactions. For instance the concept “binding” is indicative for PPI retrieval and the concept “mutation abnormality” is indicative for gene-disease associations.

Conclusion

Generic concepts are important for information retrieval and cannot be removed from semantic networks without negative impact on retrieval performance.