Modeling the Instantaneous Pressure–Volume Relation of the Left Ventricle: A Comparison of Six Models

Simulations are useful to study the heart’s ability to generate flow and the interaction between contractility and loading conditions. The left ventricular pressure–volume (PV) relation has been shown to be nonlinear, but it is unknown whether a linear model is accurate enough for simulations. Six models were fitted to the PV-data measured in five sheep and the estimated parameters were used to simulate PV-loops. Simulated and measured PV-loops were compared with the Akaike information criterion (AIC) and the Hamming distance, a measure for geometric shape similarity. The compared models were: a time-varying elastance model with fixed volume intercept (LinFix); a time-varying elastance model with varying volume intercept (LinFree); a Langewouter’s pressure-dependent elasticity model (Langew); a sigmoidal model (Sigm); a time-varying elastance model with a systolic flow-dependent resistance (Shroff) and a model with a linear systolic and an exponential diastolic relation (Burkh). Overall, the best model is LinFree (lowest AIC), closely followed by Langew. The remaining models rank: Sigm, Shroff, LinFix and Burkh. If only the shape of the PV-loops is important, all models perform nearly identically (Hamming distance between 20 and 23%). For realistic simulation of the instantaneous PV-relation a linear model suffices

IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases

Search for two Higgs bosons in final states containing two photons and two bottom quarks in proton-proton collisions at 8 TeV

Peer reviewe

Computer assisted human follicle analysis for fertility prospects with 3D ultrasound

Knowledge about the status of the female reproductive system is important for fertility problems and age-related family planning. The volume of these fertility requests in our emancipated society is steadily increasing. Intravaginal 3D ultrasound imaging of the follicles in the ovary gives important information about the ovarian aging, i.e. number of follicles, size, position and response to hormonal stimulation. Manual analysis of the many follicles is laborious and error-prone. We present a multiscale analysis to automatically detect and quantify the number and shape of the patient’s follicles. Robust estimation of the centres of the follicles in the speckled echographic images is done by calculating so-called winding number of the intensity singularity, i.e. the path integral of the angular increment of the direction of the gradient vector over a closed neighbourhood around the point. The principal edges on 200–500 intensity traces radiating from the detected singularity points are calculated by a multiscale edge focussing technique on 1D winding numbers. They are fitted with 3D spherical harmonic functions, from which the volume and shape parameters are derived

Mollusc biodiversity in late Holocene nearshore environments of the Caspian Sea: A baseline for the current biodiversity crisis

The Caspian Sea is an evolutionary island whose rich and endemic fauna have evolved in partial isolation over the past two million years. Baseline studies of pre-20th Century communities are needed in order to assess the severity of the current Caspian biodiversity crisis, which mostly involves invasive species. An inventory of late Holocene shelly assemblages (c. 2000–2500 cal yr BP) from outcrops in and around Great Turali Lake (Dagestan, Russia) shows a diverse nearshore community consisting of 24 endemic Caspian species, two invasive species and two Caspian native species that lived in a shallow embayment with mesohaline salinities of circa 5–13 psu (parts per thousands). This pre-crisis Holocene Caspian mollusc community serves as a baseline against which modern mollusc diversity measurements can be evaluated. Examination of faunas from similar environments living today and in the past illustrates the dramatic changes in nearshore communities during the 20th Century. Our study identifies a habitat that may have served as a refuge, but that is currently under threat from invasive species. The severity of the Caspian biodiversity crisis is comparable with other well-known biodiversity crises in semi-isolated ecosystems such as the cichlid fish communities of Lake Victoria, Africa.Applied Geolog

Mollusc species from the Pontocaspian region – an expert opinion list

Defining and recording the loss of species diversity is a daunting task, especially if identities of species under threat are not fully resolved. An example is the Pontocaspian biota. The mostly endemic invertebrate faunas that evolved in the Black Sea – Caspian Sea – Aral Sea region and live under variable salinity conditions are undergoing strong change, yet within several groups species boundaries are not well established. Collection efforts in the past decade have failed to produce living material of various species groups whose taxonomic status is unclear. This lack of data precludes an integrated taxonomic assessment to clarify species identities and estimate species richness of Pontocaspian biota combining morphological, ecological, genetic, and distribution data. In this paper, we present an expert-working list of Pontocaspian and invasive mollusc species associated to Pontocaspian habitats. This list is based on published and unpublished data on morphology, ecology, anatomy, and molecular biology. It allows us to (1) document Pontocaspian mollusc species, (2) make species richness estimates, and (3) identify and discuss taxonomic uncertainties. The endemic Pontocaspian mollusc species richness is estimated between 55 and 99 species, but there are several groups that may harbour cryptic species. Even though the conservation status of most of the species is not assessed or data deficient, our observations point to deterioration for many of the Pontocaspian species