High genetic variability and low local diversity in a population of arbuscular mycorrhizal fungi.

Arbuscular mycorrhizal fungi (AMF) are ecologically important root symbionts of most terrestrial plants. Ecological studies of AMF have concentrated on differences between species; largely assuming little variability within AMF species. Although AMF are clonal, they have evolved to contain a surprisingly high within-species genetic variability, and genetically different nuclei can coexist within individual spores. These traits could potentially lead to within-population genetic variation, causing differences in physiology and symbiotic function in AMF populations, a consequence that has been largely neglected. We found highly significant genetic and phenotypic variation among isolates of a population of Glomus intraradices but relatively low total observed genetic diversity. Because we maintained the isolated population in a constant environment, phenotypic variation can be considered as variation in quantitative genetic traits. In view of the large genetic differences among isolates by randomly sampling two individual spores, <50% of the total observed population genetic diversity is represented. Adding an isolate from a distant population did not increase total observed genetic diversity. Genetic variation exceeded variation in quantitative genetic traits, indicating that selection acted on the population to retain similar traits, which might be because of the multigenomic nature of AMF, where considerable genetic redundancy could buffer the effects of changes in the genetic content of phenotypic traits. These results have direct implications for ecological research and for studying AMF genes, improving commercial AMF inoculum, and understanding evolutionary mechanisms in multigenomic organisms.

Clinical consequences of imatinib plasma concentrations variability in hemato-oncologic patients

Background: Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Considering the large inter-individual differences in the function of the systems involved in its disposition, exposure to imatinib can be expected to vary widely among patients. This observational study aimed at describing imatinib pharmacokinetic variability and its relationship with various biological covariates, especially plasma alpha1-acid glycoprotein (AGP), and at exploring the concentration-response relationship in patients. Methods: A population pharmacokinetic model (NONMEM) including 321 plasma samples from 59 patients was built up and used to derive individual post-hoc Bayesian estimates of drug exposure (AUC; area under curve). Associations between AUC and therapeutic response or tolerability were explored by ordered logistic regression. Influence of the target genotype (i.e. KIT mutation profile) on response was also assessed in GIST patients. Results: A one-compartment model with first-order absorption appropriately described the data, with an average oral clearance of 14.3 L/h (CL) and volume of distribution of 347 L (Vd). A large inter-individual variability remained unexplained, both on CL (36%) and Vd (63%), but AGP levels proved to have a marked impact on total imatinib disposition. Moreover, both total and free AUC correlated with the occurrence and number of side effects (e.g. OR 2.9±0.6 for a 2-fold free AUC increase; p<0.001). Furthermore, in GIST patients, higher free AUC predicted a higher probability of therapeutic response (OR 1.9±0.5; p<0.05), notably in patients with tumor harboring an exon 9 mutation or wild-type KIT, known to decrease tumor sensitivity towards imatinib. Conclusion: The large pharmacokinetic variability, associated to the pharmacokinetic-pharmacodynamic relationship uncovered are arguments to further investigate the usefulness of individualizing imatinib prescription based on TDM. For this type of drug, it should ideally take into consideration either circulating AGP concentrations or free drug levels, as well as KIT genotype for GIST.

Prevalence of alcohol-impaired drivers based on random breath tests in a roadside survey

Sobriety checkpoints are not usually randomly located by traffic authorities. As such, information provided by non-random alcohol tests cannot be used to infer the characteristics of the general driving population. In this paper a case study is presented in which the prevalence of alcohol-impaired driving is estimated for the general population of drivers. A stratified probabilistic sample was designed to represent vehicles circulating in non-urban areas of Catalonia (Spain), a region characterized by its complex transportation network and dense traffic around the metropolis of Barcelona. Random breath alcohol concentration tests were performed during spring 2012 on 7,596 drivers. The estimated prevalence of alcohol-impaired drivers was 1.29%, which is roughly a third of the rate obtained in non-random tests. Higher rates were found on weekends (1.90% on Saturdays, 4.29% on Sundays) and especially at night. The rate is higher for men (1.45%) than for women (0.64%) and the percentage of positive outcomes shows an increasing pattern with age. In vehicles with two occupants, the proportion of alcohol-impaired drivers is estimated at 2.62%, but when the driver was alone the rate drops to 0.84%, which might reflect the socialization of drinking habits. The results are compared with outcomes in previous surveys, showing a decreasing trend in the prevalence of alcohol-impaired drivers over time.

How geographic distance and depth drive ecological variability and isolation of demersal fish communities in an archipelago system (Cape Verde, Eastern Atlantic Ocean)

Cape Verde is a tropical oceanic ecosystem, highly fragmented and dispersed, with islands physically isolated by distance and depth. To understand how isolation affects the ecological variability in this archipelago, we conducted a research project on the community structure of the 18 commercially most important demersal fishes. An index of ecological distance based on species relative dominance (Di) is developed from Catch Per Unit Effort, derived from an extensive database of artisanal fisheries. Two ecological measures of distance between islands are calculated: at the species level, DDi, and at the community level, DD (sum of DDi). A physical isolation factor (Idb) combining distance (d) and bathymetry (b) is proposed. Covariance analysis shows that isolation factor is positively correlated with both DDi and DD, suggesting that Idb can be considered as an ecological isolation factor. The effect of Idb varies with season and species. This effect is stronger in summer (May to November), than in winter (December to April), which appears to be more unstable. Species react differently to Idb, independently of season. A principal component analysis on the monthly (DDi) for the 12 islands and the 18 species, complemented by an agglomerative hierarchical clustering, shows a geographic pattern of island organization, according to Idb. Results indicate that the ecological structure of demersal fish communities of Cape Verde archipelago, both in time and space, can be explained by a geographic isolation factor. The analytical approach used here is promising and could be tested in other archipelago systems.

A theory of optimal random crackdowns

An incentives based theory of policing is developed which can explain the phenomenon of random “crackdowns,” i.e., intermittent periods of high interdiction/surveillance. For a variety of police objective functions, random crackdowns can be part of the optimal monitoring strategy. We demonstrate support for implications of the crackdown theory using traffic data gathered by the Belgian Police Department and use the model to estimate the deterrence effectof additional resources spent on speeding interdiction.

Phenotypic variability of retinocytomas: preregression and postregression growth patterns.

AIM: To describe the incidence of retinocytomas, their variability at presentation and their growth patterns both before and after regression.¦METHODS: Medical notes of the 525 patients of the Jules-Gonin Eye Hospital Retinoblastoma Clinic between 1964 and 2008 were reviewed and the charts of 36 patients with retinocytomas and/or phthisis bulbi were selected.¦RESULTS: The proportion of patients with retinocytomas and/or phthisis bulbi was 3.2%. The mean age at diagnosis was 28.7±17 years. Five tumours presented a cystic pattern (5.8%). Evidence of aggressive exophytic disease prior to spontaneous regression was documented in two eyes, and of invasive endophytic disease (regressed vitreous seeding or internal limiting membrane disruption) in three eyes. Twenty patients were followed with a mean follow-up of 44±60 months. Tumour growth was observed in 16% cases, benign cystic enlargement in 4% and malignant transformation in 12%.¦CONCLUSION: This large study of retinocytomas substantially expands the published features of retinocytoma by describing the cystic nature of some retinocytomas as well as clinical characteristics of the endophytic and exophytic preregression growth patterns. The authors report two different patterns of reactivation: benign cystic enlargement and malignant transformation with or without cystic growth. Higher than previously reported frequency of growth and possible life-threatening complications impose close lifetime follow-up of retinocytoma patients.

Natural variability of in vitro adherence to fibrinogen and fibronectin does not correlate with in vivo infectivity of Staphylococcus aureus.

Adherence to fibrinogen and fibronectin plays a crucial role in Staphylococcus aureus experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as clfA and fnbA. We set out to determine the range of adherence phenotypes in carriage isolates of S. aureus, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for in vitro adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox.

On the closed-form approximation of short-time random strike options

In this paper we propose a general technique to develop first and second order closed-form approximation formulas for short-time options withrandom strikes. Our method is based on Malliavin calculus techniques andallows us to obtain simple closed-form approximation formulas dependingon the derivative operator. The numerical analysis shows that these formulas are extremely accurate and improve some previous approaches ontwo-assets and three-assets spread options as Kirk's formula or the decomposition mehod presented in Alòs, Eydeland and Laurence (2011).