Parallel and nonparallel genome‐wide divergence among replicate population pairs of freshwater and anadromous Atlantic salmon

Little is known about the genetic basis differentiating resident and anadromous forms found in many salmonid species. Using a medium‐density SNP array, we documented genomic diversity and divergence at 2336 genetically mapped loci among three pairs of North American anadromous and freshwater Atlantic salmon populations. Our results show that across the genome, freshwater populations have lower diversity and a smaller proportion of private polymorphism relative to anadromous populations. Moreover, differentiation was more pronounced among freshwater than among anadromous populations at multiple spatial scales, suggesting a large effect of genetic drift in these isolated freshwater populations. Using nonhierarchical and hierarchical genome scans, we identified hundreds of markers spread across the genome that are potentially under divergent selection between anadromous and freshwater populations, but few outlier loci were repeatedly found in all three freshwater–anadromous comparisons. Similarly, a sliding window analysis revealed numerous regions of high divergence that were nonparallel among the three comparisons. These last results show little evidence for the parallel evolution of alleles selected for in freshwater populations, but suggest nonparallel adaptive divergence at many loci of small effects distributed through the genome. Overall, this study emphasizes the important role of genetic drift in driving genome‐wide reduction in diversity and divergence in freshwater Atlantic salmon populations and suggests a complex multigenic basis of adaptation to resident and anadromous strategies with little parallelism.     

Biomechanical models to simulate consequences of maxillofacial surgery

This paper presents the biomechanical finite element models that have been developed in the framework of the computer-assisted maxillofacial surgery. After a brief overview of the continuous elastic modelling method, two models are introduced and their use for computer-assisted applications discussed. The first model deals with orthognathic surgery and aims at predicting the facial consequences of maxillary and mandibular osteotomies. For this, a generic three-dimensional model of the face is automatically adapted to the morphology of the patient by the mean of elastic registration. Qualitative simulations of the consequences of an osteotomy of the mandible can thus be provided. The second model addresses the Sleep Apnoea Syndrome. Its aim is to develop a complete modelling of the interaction between airflow and upper airways walls during breathing. Dynamical simulations of the interaction during a respiratory cycle are computed and compared with observed phenomena.     

Beyond species area curves: application of a scale‐free measure for spatial variability of species richness

We report a novel pattern in species richness, complementary to the well‐known species–area relationship. We show that, as sample area increases, the variation in relative richness decreases among otherwise comparable spatial units. This pattern holds for southern African birds, French birds, Cape Proteaceae and the trees of Barro Colorado Island. We propose a scale‐free method for quantifying this pattern by measuring the multifractal intensity of species richness, which is the multi‐scale tendency of adjacent patches with the same area to differ in richness. By this measure, spatial variability is strongest for Cape Proteaceae and weakest for Barro Colorado Island trees. Our results have implications for area‐dependent estimates of species‐richness, for example in reserve planning and in simulation‐based studies. They imply that such estimates are most accurate for large areas, and will be subject to substantial uncertainty when the multifractal intensity is high and the area is small. For comparative purposes, multifractal intensity may be used as a supplement or as an alternative to mean richness, as well as for other ecological densities, such as biomass distribution and local abundance.     

Human 293 cell metabolism in low glutamine-supplied culture: interpretation of metabolic changes through metabolic flux analysis

Metabolic flux analysis is a useful tool to analyze cell metabolism. In this study, we report the use of a metabolic model with 34 fluxes to study the 293 cell, in order to improve its growth capacity in a DMEM/F12 medium. A batch, fed-batch with glutamine feeding, fed-batch with essential amino acids, and finally a fed-batch experiment with both essential and nonessential amino acids were compared. The fed-batch with glutamine led to a maximum cell density of 2.4x10(6) cells/ml compared to 1.8x10(6) cells/ml achieved in a batch mode. In this fed-batch with glutamine, it was also found that 2.5 mM ammonia was produced compared to the batch which had a final ammonia concentration of 1 mM. Ammonia was found to be growth inhibiting for this cell line at a concentration starting at 1 mM. During the fed-batch with glutamine, the flux analysis shows that a majority of amino acid fluxes and Kreb's cycle fluxes, except for glutamine flux, are decreased. This observation led to the conclusion that the main nutrient used is glutamine and that during the batch there is an overflow in the Kreb's cycle. Thus, a fed-batch with glutamine permits a better utilization of this nutrient. A fed-batch with essential amino acid without glutamine was also assayed in order to reduce ammonia production. The maximum cell density was increased further to 3x10(6) cells/ml and ammonia production was reduced below 1 mM. Flux analysis shows that the cells could adapt to a medium with low glutamine by increasing the amino acid fluxes toward the Kreb's cycle. Adding nonessential amino acids during this feeding strategy did not improve growth further and the nonessential amino acids accumulated in the medium.     

IL-1 family in breast cancer: Potential interplay with leptin and other adipocytokines

Obesity is associated with an increased risk of breast cancer. interleukin-1 (IL-1), a pro-inflammatory cytokine secreted by adipose tissue, is involved in breast cancer development. There is also convincing evidence that other adipocytokines including leptin not only have a role in haematopoiesis, reproduction and immunity but are also growth factors in cancer. Therefore, IL-1 family and leptin family are adipocytokines which could represent a major link between obesity and breast cancer progression. This minireview provides insight into recent findings on the prognostic significance of IL-1 and leptin in mammary tumours, and discusses the potential interplay between IL-1 family members and adipocyte-derived hormones in breast cancer.     

Blood T lymphocyte populations in the hemophiliac

We have studied a group of 31 hemophiliac patients (hemophilia A: 26 patients, hemophilia B: 5 patients); 29 healthy men were used as controls. Hemophiliac patients had increased percentages of suppressor T-lymphocytes and depressed T4/T8 ratios. These abnormalities were found to be significantly correlated with the amount of F VIII used per year.     

Ruling out pulmonary embolism across different healthcare settings: A systematic review and individual patient data meta-analysis

BackgroundThe challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings.Methods and findingsWe performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care (n = 12,612), primary healthcare clinics (n = 3,174), referred secondary care (n = 17,052), and hospitalized or nursing home patients (n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the “failure rate” of each strategy—i.e., the proportion of missed PE among patients categorized as “PE excluded” and “efficiency”—defined as the proportion of patients categorized as “PE excluded” among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust.ConclusionsThe capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy.

Geert-Jan Geersing and colleagues assess the capability of ruling-out pulmonary embolism by available diagnostic strategies across a range of healthcare settings.