Genome-wide association study for calving performance using high-density genotypes in dairy and beef cattle

peer-reviewedBackground Calving difficulty and perinatal mortality are prevalent in modern-day cattle production systems. It is well-established that there is a genetic component to both traits, yet little is known about their underlying genomic architecture, particularly in beef breeds. Therefore, we performed a genome-wide association study using high-density genotypes to elucidate the genomic architecture of these traits and to identify regions of the bovine genome associated with them. Results Genomic regions associated with calving difficulty (direct and maternal) and perinatal mortality were detected using two statistical approaches: (1) single-SNP (single nucleotide polymorphism) regression and (2) a Bayesian approach. Data included high-density genotypes on 770 Holstein-Friesian, 927 Charolais and 963 Limousin bulls. Several novel or previously identified genomic regions were detected but associations differed by breed. For example, two genomic associations, one each on chromosomes 18 and 2 explained 2.49 % and 3.13 % of the genetic variance in direct calving difficulty in the Holstein-Friesian and Charolais populations, respectively. Imputed Holstein-Friesian sequence data was used to refine the genomic regions responsible for significant associations. Several candidate genes on chromosome 18 were identified and four highly significant missense variants were detected within three of these genes (SIGLEC12, CTU1, and ZNF615). Nevertheless, only CTU1 contained a missense variant with a putative impact on direct calving difficulty based on SIFT (0.06) and Polyphen (0.95) scores. Using imputed sequence data, we refined a genomic region on chromosome 4 associated with maternal calving difficulty in the Holstein-Friesian population and found the strongest association with an intronic variant in the PCLO gene. A meta-analysis was performed across the three breeds for each calving performance trait to identify common variants associated with these traits in the three breeds. Our results suggest that a portion of the genetic variation in calving performance is common to all three breeds. Conclusion The genomic architecture of calving performance is complex and mainly influenced by many polymorphisms of small effect. We identified several associations of moderate effect size but the majority were breed-specific, indicating that breed-specific alleles exist for calving performance or that the linkage phase between genotyped allele and causal mutation varies between breeds

Benthic Foraminiferal response to sea level change in the mixed siliciclastic-carbonate system of southern Ashmore Trough (Gulf of Papua)

Ashmore Trough in the western Gulf of Papua (GoP) represents an outstanding modern example of a tropical mixed siliciclastic-carbonate depositional system where significant masses of both river-borne silicates and bank-derived neritic carbonates accumulate. In this study, we examine how benthic foraminiferal populations within Ashmore Trough vary in response to sea level–driven paleoenvironmental changes, particularly organic matter and sediment supply. Two 11.3-m-long piston cores and a trigger core were collected from the slope of Ashmore Trough and dated using radiocarbon and oxygen isotope measurements of planktic foraminifera. Relative abundances, principal component analyses, and cluster analyses of benthic foraminiferal assemblages in sediment samples identify three distinct assemblages whose proportions changed over time. Assemblage 1, with high abundances of Uvigerina peregrina and Bolivina robusta, dominated between ∼83 and 70 ka (early regression); assemblage 2, with high abundances of Globocassidulina subglobosa, dominated between ∼70 and 11 ka (late regression through lowstand and early transgression); and assemblage 3, with high abundances of neritic benthic species such as Planorbulina mediterranensis, dominated from ∼11 ka to the present (late transgression through early highstand). Assemblage 1 represents heightened organic carbon flux or lowered bottom water oxygen concentration, and corresponds to a time of maximum siliciclastic fluxes to the slope with falling sea level. Assemblage 2 reflects lowered organic carbon flux or elevated bottom water oxygen concentration, and corresponds to an interval of lowered siliciclastic fluxes to the slope due to sediment bypass during sea level lowstand. Assemblage 3 signals increased off-shelf delivery of neritic carbonates, likely when carbonate productivity on the outer shelf (Great Barrier Reef) increased significantly when it was reflooded. Benthic foraminiferal assemblages in the sediment sink (slopes of Ashmore Trough) likely respond to the amount and type of sediment supplied from the proximal source (outer GoP shelf)

In silico evaluation and optimisation of magnetic resonance elastography of the liver

Objective. Magnetic resonance elastography (MRE) is widely adopted as a biomarker of liver fibrosis. However, in vivo MRE accuracy is difficult to assess. Approach. Finite element model (FEM) simulation was employed to evaluate liver MRE accuracy and inform methodological optimisation. MRE data was simulated in a 3D FEM of the human torso including the liver, and compared with spin-echo echo-planar imaging MRE acquisitions. The simulated MRE results were compared with the ground truth magnitude of the complex shear modulus (∣G*∣) for varying: (1) ground truth liver ∣G*∣; (2) simulated imaging resolution; (3) added noise; (4) data smoothing. Motion and strain-based signal-to-noise (SNR) metrics were evaluated on the simulated data as a means to select higher-quality voxels for preparation of acquired MRE summary statistics of ∣G*∣. Main results. The simulated MRE accuracy for a given ground truth ∣G*∣ was found to be a function of imaging resolution, motion-SNR and smoothing. At typical imaging resolutions, it was found that due to under-sampling of the MRE wave-field, combined with motion-related noise, the reconstructed simulated ∣G*∣ could contain errors on the scale of the difference between liver fibrosis stages, e.g. 54% error for ground truth ∣G*∣ = 1 kPa. Optimum imaging resolutions were identified for given ground truth ∣G*∣ and motion-SNR levels. Significance. This study provides important knowledge on the accuracy and optimisation of liver MRE. For example, for motion-SNR ≤ 5, to distinguish between liver ∣G*∣ of 2 and 3 kPa (i.e. early-stage liver fibrosis) it was predicted that the optimum isotropic voxel size is 4–6 mm

A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics

Background & aimsBlood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output.MethodsHealthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging.ResultsTen of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index.ConclusionsA smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid

Perception and automatic detection of wind-induced microphone noise

Wind can induce noise on microphones, causing problems for users of hearing aids and for those making recordings outdoors. Perceptual tests in the laboratory and via the Internet were carried out to understand what features of wind noise are important to the perceived audio quality of speech recordings. The average A-weighted sound pressure level of the wind noise was found to dominate the perceived degradation of quality, while gustiness was mostly unimportant. Large degradations in quality were observed when the signal to noise ratio was lower than about 15 09dB. A model to allow an estimation of wind noise level was developed using an ensemble of decision trees. The model was designed to work with a single microphone in the presence of a variety of foreground sounds. The model outputted four classes of wind noise: none, low, medium, and high. Wind free examples were accurately identified in 79% of cases. For the three classes with noise present, on average 93% of samples were correctly assigned. A second ensemble of decision trees was used to estimate the signal to noise ratio and thereby infer the perceived degradation caused by wind noise

Determinants of Acceptance of Cervical Cancer Screening in Dar es Salaam, Tanzania.

To describe how demographic characteristics and knowledge of cervical cancer influence screening acceptance among women living in Dar es Salaam, Tanzania. Multistage cluster sampling was carried out in 45 randomly selected streets in Dar es Salaam. Women between the ages of 25-59 who lived in the sampled streets were invited to a cervical cancer screening; 804 women accepted and 313 rejected the invitation. Information on demographic characteristics and knowledge of cervical cancer were obtained through structured questionnaire interviews. Women aged 35-44 and women aged 45-59 had increased ORs of 3.52 and 7.09, respectively, for accepting screening. Increased accepting rates were also found among single women (OR 2.43) and among women who had attended primary or secondary school (ORs of 1.81 and 1.94). Women who had 0-2 children were also more prone to accept screening in comparison with women who had five or more children (OR 3.21). Finally, knowledge of cervical cancer and awareness of the existing screening program were also associated with increased acceptance rates (ORs of 5.90 and 4.20). There are identifiable subgroups where cervical cancer screening can be increased in Dar es Salaam. Special attention should be paid to women of low education and women of high parity. In addition, knowledge and awareness raising campaigns that goes hand in hand with culturally acceptable screening services will likely lead to an increased uptake of cervical cancer screening

Spot the difference: Comparing results of analyses from real patient data and synthetic derivatives

BACKGROUND: Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification. OBJECTIVES: To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd., Beer Sheva, Israel) for its ability to produce data that can be used for research purposes while obviating privacy and confidentiality concerns. METHODS: We explored three use cases and tested the robustness of synthetic data by comparing the results of analyses using synthetic derivatives to analyses using the original data using traditional statistics, machine learning approaches, and spatial representations of the data. We designed these use cases with the purpose of conducting analyses at the observation level (Use Case 1), patient cohorts (Use Case 2), and population-level data (Use Case 3). RESULTS: For each use case, the results of the analyses were sufficiently statistically similar ( DISCUSSION AND CONCLUSION: This article presents the results of each use case and outlines key considerations for the use of synthetic data, examining their role in clinical research for faster insights and improved data sharing in support of precision healthcare

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials