Estimating gene flow across hybrid zones: how reliable are microsatellites?

Due to their high polymorphism, microsatellites have become one of the most valued genetic markers in population biology. We review the first two published studies on hybrid zones of the common shrew based on microsatellites. Both reveal surprisingly high interracial gene flow. It can be shown that these are overestimates. Indeed, in classical population genetics models as F-statistics, mutation is neglected. This constitutes an acceptable assumption as long as migration is higher than mutation. However, in hybrid zones where genetic exchanges can be rare, neglecting mutation will lead to strong overestimates of migration when working with microsatellites which display mutation rates up to 10(-3). As there seems to be no straightforward way to correct for this bias, interracial gene flow estimates based on microsatellites should be taken with caution. This problem should however not conceal the enormous potential of microsatellites to unravel the genetics of hybrid zones.

Wheat alleles introgress into selfing wild relatives: empirical estimates from approximate Bayesian computation in Aegilops triuncialis.

Extensive gene flow between wheat (Triticum sp.) and several wild relatives of the genus Aegilops has recently been detected despite notoriously high levels of selfing in these species. Here, we assess and model the spread of wheat alleles into natural populations of the barbed goatgrass (Aegilops triuncialis), a wild wheat relative prevailing in the Mediterranean flora. Our sampling, based on an extensive survey of 31 Ae. triuncialis populations collected along a 60 km × 20 km area in southern Spain (Grazalema Mountain chain, Andalousia, totalling 458 specimens), is completed with 33 wheat cultivars representative of the European domesticated pool. All specimens were genotyped with amplified fragment length polymorphism with the aim of estimating wheat admixture levels in Ae. triuncialis populations. This survey first confirmed extensive hybridization and backcrossing of wheat into the wild species. We then used explicit modelling of populations and approximate Bayesian computation to estimate the selfing rate of Ae. triuncialis along with the magnitude, the tempo and the geographical distance over which wheat alleles introgress into Ae. triuncialis populations. These simulations confirmed that extensive introgression of wheat alleles (2.7 × 10(-4) wheat immigrants for each Ae. triuncialis resident, at each generation) into Ae. triuncialis occurs despite a high selfing rate (Fis ≈ 1 and selfing rate = 97%). These results are discussed in the light of risks associated with the release of genetically modified wheat cultivars in Mediterranean agrosystems.

Quantification of Myocardial Blood Flow in Absolute Terms Using (82)Rb PET Imaging: The RUBY-10 Study.

OBJECTIVES: The purpose of this study was to compare myocardial blood flow (MBF) and myocardial flow reserve (MFR) estimates from rubidium-82 positron emission tomography ((82)Rb PET) data using 10 software packages (SPs) based on 8 tracer kinetic models. BACKGROUND: It is unknown how MBF and MFR values from existing SPs agree for (82)Rb PET. METHODS: Rest and stress (82)Rb PET scans of 48 patients with suspected or known coronary artery disease were analyzed in 10 centers. Each center used 1 of 10 SPs to analyze global and regional MBF using the different kinetic models implemented. Values were considered to agree if they simultaneously had an intraclass correlation coefficient >0.75 and a difference <20% of the median across all programs. RESULTS: The most common model evaluated was the Ottawa Heart Institute 1-tissue compartment model (OHI-1-TCM). MBF values from 7 of 8 SPs implementing this model agreed best. Values from 2 other models (alternative 1-TCM and Axially distributed) also agreed well, with occasional differences. The MBF results from other models (e.g., 2-TCM and retention) were less in agreement with values from OHI-1-TCM. CONCLUSIONS: SPs using the most common kinetic model-OHI-1-TCM-provided consistent results in measuring global and regional MBF values, suggesting that they may be used interchangeably to process data acquired with a common imaging protocol.

Extension of Murray's law using a non-Newtonian model of blood flow.

BACKGROUND: So far, none of the existing methods on Murray's law deal with the non-Newtonian behavior of blood flow although the non-Newtonian approach for blood flow modelling looks more accurate. MODELING: In the present paper, Murray's law which is applicable to an arterial bifurcation, is generalized to a non-Newtonian blood flow model (power-law model). When the vessel size reaches the capillary limitation, blood can be modeled using a non-Newtonian constitutive equation. It is assumed two different constraints in addition to the pumping power: the volume constraint or the surface constraint (related to the internal surface of the vessel). For a seek of generality, the relationships are given for an arbitrary number of daughter vessels. It is shown that for a cost function including the volume constraint, classical Murray's law remains valid (i.e. SigmaR(c) = cste with c = 3 is verified and is independent of n, the dimensionless index in the viscosity equation; R being the radius of the vessel). On the contrary, for a cost function including the surface constraint, different values of c may be calculated depending on the value of n. RESULTS: We find that c varies for blood from 2.42 to 3 depending on the constraint and the fluid properties. For the Newtonian model, the surface constraint leads to c = 2.5. The cost function (based on the surface constraint) can be related to entropy generation, by dividing it by the temperature. CONCLUSION: It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid.

High-performance liquid chromatography of the renal blood flow marker p-aminohippuric acid (PAH) and its metabolite N-acetyl PAH improves PAH clearance measurements.

PAH (N-(4-aminobenzoyl)glycin) clearance measurements have been used for 50 years in clinical research for the determination of renal plasma flow. The quantitation of PAH in plasma or urine is generally performed by colorimetric method after diazotation reaction but the measurements must be corrected for the unspecific residual response observed in blank plasma. We have developed a HPLC method to specifically determine PAH and its metabolite NAc-PAH using a gradient elution ion-pair reversed-phase chromatography with UV detection at 273 and 265 nm, respectively. The separations were performed at room temperature on a ChromCart (125 mmx4 mm I.D.) Nucleosil 100-5 microm C18AB cartridge column, using a gradient elution of MeOH-buffer pH 3.9 1:99-->15:85 over 15 min. The pH 3.9 buffered aqueous solution consisted in a mixture of 375 ml sodium citrate-citric acid solution (21.01 g citric acid and 8.0 g NaOH per liter), added up with 2.7 ml H3PO4 85%, 1.0 g of sodium heptanesulfonate and completed ad 1000 ml with ultrapure water. The N-acetyltransferase activity does not seem to notably affect PAH clearances, although NAc-PAH represents 10.2+/-2.7% of PAH excreted unchanged in 12 healthy subjects. The performance of the HPLC and the colorimetric method have been compared using urine and plasma samples collected from healthy volunteers. Good correlations (r=0.94 and 0.97, for plasma and urine, respectively) are found between the results obtained with both techniques. However, the colorimetric method gives higher concentrations of PAH in urine and lower concentrations in plasma than those determined by HPLC. Hence, both renal (ClR) and systemic (Cls) clearances are systematically higher (35.1 and 17.8%, respectively) with the colorimetric method. The fraction of PAH excreted by the kidney ClR/ClS calculated from HPLC data (n=143) is, as expected, always <1 (mean=0.73+/-0.11), whereas the colorimetric method gives a mean extraction ratio of 0.87+/-0.13 implying some unphysiological values (>1). In conclusion, HPLC not only enables the simultaneous quantitation of PAH and NAc-PAH, but may also provide more accurate and precise PAH clearance measurements.

Acting, predicting and intervening in a socio-hydrological world

This paper asks a simple question: if humans and their actions co-evolve with hydrological systems (Sivapalan et al., 2012), what is the role of hydrological scientists, who are also humans, within this system? To put it more directly, as traditionally there is a supposed separation of scientists and society, can we maintain this separation as socio-hydrologists studying a socio-hydrological world? This paper argues that we cannot, using four linked sections. The first section draws directly upon the concern of science-technology studies to make a case to the (socio-hydrological) community that we need to be sensitive to constructivist accounts of science in general and socio-hydrology in particular. I review three positions taken by such accounts and apply them to hydrological science, supported with specific examples: (a) the ways in which scientific activities frame socio-hydrological research, such that at least some of the knowledge that we obtain is constructed by precisely what we do; (b) the need to attend to how socio-hydrological knowledge is used in decision-making, as evidence suggests that hydrological knowledge does not flow simply from science into policy; and (c) the observation that those who do not normally label themselves as socio-hydrologists may actually have a profound knowledge of socio-hydrology. The second section provides an empirical basis for considering these three issues by detailing the history of the practice of roughness parameterisation, using parameters like Manning's n, in hydrological and hydraulic models for flood inundation mapping. This history sustains the third section that is a more general consideration of one type of socio-hydrological practice: predictive modelling. I show that as part of a socio-hydrological analysis, hydrological prediction needs to be thought through much more carefully: not only because hydrological prediction exists to help inform decisions that are made about water management; but also because those predictions contain assumptions, the predictions are only correct in so far as those assumptions hold, and for those assumptions to hold, the socio-hydrological system (i.e. the world) has to be shaped so as to include them. Here, I add to the ``normal'' view that ideally our models should represent the world around us, to argue that for our models (and hence our predictions) to be valid, we have to make the world look like our models. Decisions over how the world is modelled may transform the world as much as they represent the world. Thus, socio-hydrological modelling has to become a socially accountable process such that the world is transformed, through the implications of modelling, in a fair and just manner. This leads into the final section of the paper where I consider how socio-hydrological research may be made more socially accountable, in a way that is both sensitive to the constructivist critique (Sect. 1), but which retains the contribution that hydrologists might make to socio-hydrological studies. This includes (1) working with conflict and controversy in hydrological science, rather than trying to eliminate them; (2) using hydrological events to avoid becoming locked into our own frames of explanation and prediction; (3) being empirical and experimental but in a socio-hydrological sense; and (4) co-producing socio-hydrological predictions. I will show how this might be done through a project that specifically developed predictive models for making interventions in river catchments to increase high river flow attenuation. Therein, I found myself becoming detached from my normal disciplinary networks and attached to the co-production of a predictive hydrological model with communities normally excluded from the practice of hydrological science.

Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

Combining niche modelling and landscape genetics to study local adaptation: A novel approach illustrated using alpine plants

Understanding the factors that shape adaptive genetic variation across species niches has become of paramount importance in evolutionary ecology, especially to understand how adaptation to changing climate affects the geographic range of species. The distribution of adaptive alleles in the ecological niche is determined by the emergence of novel mutations, their fitness consequences and gene flow that connects populations across species niches. Striking demographical differences and source sink dynamics of populations between the centre and the margin of the niche can play a major role in the emergence and spread of adaptive alleles. Although some theoretical predictions have long been proposed, the origin and distribution of adaptive alleles within species niches remain untested. In this paper, we propose and discuss a novel empirical approach that combines landscape genetics with species niche modelling, to test whether alleles that confer local adaptation are more likely to occur in either marginal or central populations of species niches. We illustrate this new approach by using a published data set of 21 alpine plant species genotyped with a total of 2483 amplified fragment length polymorphisms (AFLP), distributed over more than 1733 sampling sites across the Alps. Based on the assumption that alleles that were statistically associated with environmental variables were adaptive, we found that adaptive alleles in the margin of a species niche were also present in the niche centre, which suggests that adaptation originates in the niche centre. These findings corroborate models of species range evolution, in which the centre of the niche contributes to the emergence of novel adaptive alleles, which diffuse towards niche margins and facilitate niche and range expansion through subsequent local adaptation. Although these results need to be confirmed via fitness measurements in natural populations and functionally characterised genetic sequences, this study provides a first step towards understanding how adaptive genetic variation emerges and shapes species niches and geographic ranges along environmental gradients.