QTLMAS 2009: simulated dataset

Background - The simulation of the data for the QTLMAS 2009 Workshop is described. Objective was to simulate observations from a growth curve which was influenced by a number of QTL. Results - The data consisted of markers, phenotypes and pedigree. Genotypes of 453 markers, distributed over 5 chromosomes of 1 Morgan each, were simulated for 2,025 individuals. From those, 25 individuals were parents of the other 2,000 individuals. The 25 parents were genetically related. Phenotypes were simulated according to a logistic growth curve and were made available for 1,000 of the 2,000 offspring individuals. The logistic growth curve was specified by three parameters. Each parameter was influenced by six Quantitative Trait Loci (QTL), positioned at the five chromosomes. For each parameter, one QTL had a large effect and five QTL had small effects. Variance of large QTL was five times the variance of small QTL. Simulated data was made available at http://www.qtlmas2009.wur.nl/UK/Dataset

Comparison of analyses of the QTLMAS XIII common dataset. I: genomic selection

Background - Genomic selection, the use of markers across the whole genome, receives increasing amounts of attention and is having more and more impact on breeding programs. Development of statistical and computational methods to estimate breeding values based on markers is a very active area of research. A simulated dataset was analyzed by participants of the QTLMAS XIII workshop, allowing a comparison of the ability of different methods to estimate genomic breeding values. Methods - A best case scenario was analyzed by the organizers where QTL genotypes were known. Participants submitted estimated breeding values for 1000 unphenotyped individuals together with a description of the applied method(s). The submitted breeding values were evaluated for correlation with the simulated values (accuracy), rank correlation of the best 10% of individuals and error in predictions. Bias was tested by regression of simulated on estimated breeding values. Results - The accuracy obtained from the best case scenario was 0.94. Six research groups submitted 19 sets of estimated breeding values. Methods that assumed the same variance for markers showed accuracies, measured as correlations between estimated and simulated values, ranging from 0.75 to 0.89 and rank correlations between 0.58 and 0.70. Methods that allowed different marker variances showed accuracies ranging from 0.86 to 0.94 and rank correlations between 0.69 and 0.82. Methods assuming equal marker variances were generally more biased and showed larger prediction errors. Conclusions - The best performing methods achieved very high accuracies, close to accuracies achieved in a best case scenario where QTL genotypes were known without error. Methods that allowed different marker variances generally outperformed methods that assumed equal marker variances. Genomic selection methods performed well compared to traditional, pedigree only, methods; all methods showed higher accuracies than those obtained for breeding values estimated solely on pedigree relationship

Novel Properties of The Apparent Metal-Insulator Transition in Two-Dimensional Systems

The low-temperature conductivity of low-density, high-mobility, two-dimensional hole systems in GaAs was studied. We explicitly show that the metal-insulator transition, observed in these systems, is characterized by a well-defined critical density, p_0c. We also observe that the low-temperature conductivity of these systems depends linearly on the hole density, over a wide density range. The high-density linear conductivity extrapolates to zero at a density close to the critical density.Comment: 4 Figure

Impact of the new European Union In Vitro Diagnostics Regulation on the practice of hospital diagnostic laboratories.

OBJECTIVES: The In Vitro Diagnostics Regulation 2017/746 (IVDR) coming into force from May 2022, creates the first European regulatory recognition for biomarker tests linked to medicinal products, so-called companion diagnostics (CDx). Since the introduction of the IVDR is associated with uncertainties about its impact on hospital practice, it is urgent and valuable to investigate how and why CDx are currently used in hospital practice, which factors influence the choice for applying in-house or commercial CDx, and what the expectations are about how the IVDR may affect current practice. METHODS: We investigated these questions using an interview-based approach and focused on 15 hospital laboratories in the Netherlands, including 7 academic and 8 general hospitals. All types of CDx were considered relevant for this research, including both genetic and protein-based biomarkers. RESULTS: Factors found included: costs and convenience, complexity of application, and compatibility with existing workflows. Next to in-house and commercial CDx, hospital laboratories addressed compatibility by tweaking existing CDx. CONCLUSION: Although increased quality of CDx is welcomed, worries toward increased costs and administrative work, and decreased quality were expressed. Further, the IVDR might also hinder using optimized in-house and tweaked CDx. Additionally, increased administrative burden could decrease innovativeness toward CDx

Scaling of the Conductivity with Temperature and Uniaxial Stress in Si:B at the Metal-Insulator Transition

Using uniaxial stress to tune Si:B through the metal-insulator transition we find the conductivity at low temperatures shows an excellent fit to scaling with temperature and stress on both sides of the transition. The scaling functions yield the conductivity in the metallic and insulating phases, and allow a reliable determination of the temperature dependence in the critical regions on both sides of the transition

Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis

Background/Aims: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. Methods: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. Results: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. Conclusions: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies. Copyright (c) 2006 S. Karger AG, Basel

Conductivity of Metallic Si:B near the Metal-Insulator Transition: Comparison between Unstressed and Uniaxially Stressed Samples

The low-temperature dc conductivities of barely metallic samples of p-type Si:B are compared for a series of samples with different dopant concentrations, n, in the absence of stress (cubic symmetry), and for a single sample driven from the metallic into the insulating phase by uniaxial compression, S. For all values of temperature and stress, the conductivity of the stressed sample collapses onto a single universal scaling curve. The scaling fit indicates that the conductivity of si:B is proportional to the square-root of T in the critical range. Our data yield a critical conductivity exponent of 1.6, considerably larger than the value reported in earlier experiments where the transition was crossed by varying the dopant concentration. The larger exponent is based on data in a narrow range of stress near the critical value within which scaling holds. We show explicitly that the temperature dependences of the conductivity of stressed and unstressed Si:B are different, suggesting that a direct comparison of the critical behavior and critical exponents for stress- tuned and concentration-tuned transitions may not be warranted

Cytoreductive Surgery with the PlasmaJet Improved Quality-of-Life for Advanced Stage Ovarian Cancer Patients

Background: Knowledge of quality-of-life after cytoreductive surgery is important to counsel patients with advanced-stage epithelial ovarian cancer prior to surgery. The aim of this study was to determine whether the use of the PlasmaJet Surgical device during cytoreductive surgery has an effect on the quality-of-life of patients with advanced epithelial ovarian cancer. Methods: Data included in this prospective observational study were derived from the PlaComOv study, in which patients with advanced epithelial ovarian cancer were randomly assigned to have cytoreductive surgery with or without adjuvant use of the PlasmaJet. Quality-of-life was measured before surgery and one, six, 12, and 24 months after surgery with three questionnaires: the EORTC QLQ-C30, QLQ-OV28, and EQ-5D-5L. Results: Between 2018 and 2020, 326 patients were enrolled in the trial. The overall response rate was high, with the lowest response rate at 24 months of 77%. At 6 months, quality-of-life was higher in the intervention group (95%CI 0.009; 0.081, p = 0.045). At 12 months, quality-of-life was higher in the intervention group with fewer symptoms of fatigue, appetite loss, and diarrhea (95%CI 0.6; 10,0, p = 0.027); similarly, patients in the intervention group reported a better body image (95%CI −14.2; −3.0, p = 0.003) and a higher score on the visual analog scale (95%CI 1.99; 11.15, p = 0.005). At 24 months postoperatively, no further difference was found between the two groups except for pain (95%CI −12.9; −0.8, p = 0.027) and body image (95%CI −13.808; −0.733, p = 0.029). A higher quality-of-life in the intervention group was partially explained by the mediator ‘surgery outcome’. Conclusions: This study demonstrated knowledge of patients’ quality-of-life until two years after cytoreductive surgery. The use of the PlasmaJet Surgical device during cytoreductive surgery leads to a higher quality-of-life than conventional surgery with electrocoagulation alone. Even after adjustment for the mediator of surgical outcome, a higher quality-of-life was seen in patients who had surgery with the use of the PlasmaJet device.</p

Contemporary human H3N2 influenza a viruses require a low threshold of suitable glycan receptors for efficient infection

Recent human H3N2 influenza A viruses (IAV) have evolved to employ elongated glycans terminating in α2,6-linked sialic acid as their receptors. These glycans are displayed in low abundancies by (humanized) Madin-Darby Canine Kidney cells (MDCK and hCK) which are commonly employed to propagate IAV, resulting in low or no viral propagation. Here, we examined whether the overexpression of the glycosyltransferases B3GNT2 and B4GALT1, which are responsible for the elongation of poly-N-acetyllactosamines (LacNAc), would result in improved A/H3N2 propagation. Stable overexpression of B3GNT2 and B4GALT1 in MDCK and hCK cells was achieved by lentiviral integration and subsequent antibiotic selection and confirmed by qPCR and protein mass spectrometry experiments. Flow cytometry and glycan mass spectrometry experiments using the B3GNT2 and/or B4GALT1 knock-in cells demonstrated increased binding of viral hemagglutinins and the presence of a larger number of LacNAc repeating units, especially on hCK-B3GNT2 cells. An increase in the number of glycan receptors did, however, not result in a greater infection efficiency of recent human H3N2 viruses. Based on these results, we propose that H3N2 IAVs require a low number of suitable glycan receptors to infect cells and that an increase in the glycan receptor display above this threshold does not result in improved infection efficiency