A cost-effective strategy for nonoscillatory convection without clipping

Clipping of narrow extrema and distortion of smooth profiles is a well known problem associated with so-called high resolution nonoscillatory convection schemes. A strategy is presented for accurately simulating highly convective flows containing discontinuities such as density fronts or shock waves, without distorting smooth profiles or clipping narrow local extrema. The convection algorithm is based on non-artificially diffusive third-order upwinding in smooth regions, with automatic adaptive stencil expansion to (in principle, arbitrarily) higher order upwinding locally, in regions of rapidly changing gradients. This is highly cost effective because the wider stencil is used only where needed-in isolated narrow regions. A recently developed universal limiter assures sharp monotonic resolution of discontinuities without introducing artificial diffusion or numerical compression. An adaptive discriminator is constructed to distinguish between spurious overshoots and physical peaks; this automatically relaxes the limiter near local turning points, thereby avoiding loss of resolution in narrow extrema. Examples are given for one-dimensional pure convection of scalar profiles at constant velocity

The effect of preincubation time and myo-inositol supplementation on the quality of mouse mii oocytes

Background: It is demonstrated that optimal preincubation time improves oocyte quality, fertilization potential and developmental rate. This study aimed to evaluate the effect of preincubation time in the simple and myo-inositol supplemented medium on the oocyte quality regarding oxidative stress and mitochondrial alteration. Methods: Cumulus oocyte complexes (COCs) retrieved from superovulated NMRI mice were divided in groups of 0, 4 and 8 hr preincubation time in the simple and 20 mmol/L myo-inositol supplemented media. Intracellular reactive oxygen species (H2O2), glutathione (GSH), mitochondrial membrane potential (MMP), ATP content, and mitochondrial amount were measured and analyzed in experimental groups. One-way ANOVA and Kruskal-Wallis were respectively used for parametric and nonparametric variables. Statistical significance was defined as p<0.05. Results: In comparison to control group, variables including ROS, GSH, mitochondrial amount, fertilization and developmental rates were significantly changed after 4 hr of preincubation in the simple medium, while MMP decreased following 8 hr of preincubation in the simple medium (p<0.001). Preincubation of oocytes up to 8 hr in the simple medium could not decrease ATP content. For both 4 and 8 hr preincubation times, myo-inositole could decrease H2O2 and increase GSH and MMP levels and consequently could improve fertilization rate compared to oocytes preincubated in the simple culture. Conclusion: It seems that 4 hr or more preincubation time can decrease the oocyte quality and lead to reduced oocyte fertilization and developmental potential. Howevere, myo-inositol may prevent oocyte quality reduction and improve fertilization potential in comparision to the equivalent simple groups. © 2020 Avicenna Research Institute. All rights reserved

Cell Dispersal Influences Tumor Heterogeneity and Introduces a Bias in NGS Data Interpretation

Short and long distance cell dispersal can have a marked effect on tumor structure, high cellular motility could lead to faster cell mixing and lower observable intratumor heterogeneity. Here we evaluated a model for cell mixing that investigates how short-range dispersal and cell turnover will account for mutational proportions. We show that cancer cells can penetrate neighboring and distinct areas in a matter of days. In next generation sequencing runs, higher proportions of a given cell line generated frequencies with higher precision, while mixtures with lower amounts of each cell line had lower precision manifesting in higher standard deviations. When multiple cell lines were co-cultured, cellular movement altered observed mutation frequency by up to 18.5%. We propose that some of the shared mutations detected at low allele frequencies represent highly motile clones that appear in multiple regions of a tumor owing to dispersion throughout the tumor. In brief, cell movement will lead to a significant technical (sampling) bias when using next generation sequencing to determine clonal composition. A possible solution to this drawback would be to radically decrease detection thresholds and increase coverage in NGS analyses. © 2017 The Author(s)

A “rotating menu” of medical uncertainty for families affected by telomere biology disorders: A qualitative interview study

Background Medical uncertainty may cause distress and challenge medical decision-making for patients with rare diseases and their caregivers. Few studies have examined the experience and management of medical uncertainty in rare disease and the dynamics of multiple medical uncertainty sources, issues, and management strategies. Objective We explored the experience and management of uncertainty in individuals with telomere biology disorders (TBDs), a set of rare cancer-prone bone marrow failure syndromes, and their caregivers. Design Participants (N=32) in this qualitative-descriptive study were individuals with a TBD (n=17) and/or their caregivers (n=15). We thematically analyzed transcripts to describe the presence and dynamics of medical uncertainty in TBDs using categories from a previously published taxonomy. Results Individuals with TBDs and caregivers described medical uncertainty as a chronic burden embodied amidst a range of interrelated sources and issues. Scientific uncertainty included diagnostic and prognostic ambiguity. Practical uncertainty focused on logistical challenges of building and maintaining medical care teams. Personal uncertainty included difficulty realigning self-identity, goals, and relationship expectations post-diagnosis. Scientific, practical, and personal uncertainty issues were entangled. The rarity of TBDs resulted in limited scientific knowledge, which gave rise to practical and personal uncertainties affecting medical decision-making and relationship formation (e.g., creating trusted care teams where patient knowledge of TBDs may exceed that of clinicians). Participants used multiple strategies for uncertainty management, particularly information-seeking and community-building. However, these management strategies could intensify, rather than resolve, participants’ medical uncertainty. Conclusion In TBDs, medical uncertainty manifests as a network of multiple, interrelated, sources and issues, which require evolving management strategies. Researchers must be mindful that complex, synergistic uncertainty networks contribute to psychosocial challenges in TBDs. Additional research is warranted to address scientific uncertainty in TBDs, including clinical manifestations and underlying biology, and to develop psychosocial interventions that recognize and anticipate evolving uncertainty

Genomic characterization of malignant progression in neoplastic pancreatic cysts

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention

Who is behind the Model? Classifying Modelers based on Pragmatic Model Features

\u3cp\u3eProcess modeling tools typically aid end users in generic, non-personalized ways. However, it is well conceivable that different types of end users may profit from different types of modeling support. In this paper, we propose an approach based on machine learning that is able to classify modelers regarding their expertise while they are creating a process model. To do so, it takes into account pragmatic features of the model under development. The proposed approach is fully automatic, unobtrusive, tool independent, and based on objective measures. An evaluation based on two data sets resulted in a prediction performance of around 90%. Our results further show that all features can be efficiently calculated, which makes the approach applicable to online settings like adaptive modeling environments. In this way, this work contributes to improving the performance of process modelers.\u3c/p\u3

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods

The Etiology of Acute Renal Failure in the Newborn Infants Admitted to the NICU at Afzalipour Medical Centre, Kerman, IRAN

Abstract: Introduction: Despite the countless benefits of breast milk, each year many infants are admitted to NICU's with clinical symptoms and laboratory indicators of dehydration and renal failure due to the lack of a national program to monitor post discharge breastfeeding over the first few days of life. In addition to identifying the role of inadequate breast milk intake as a cause of renal failure, the purpose of this study was to assess causes, clinical presentations and laboratory tests in acute renal failure and to identify the most available and practical laboratory test to differentiate prerenal from renal azotemia. Methods: A cross-sectional prospective study was performed between April 2005 and May 2006 (14 months) at Afzalipour Medical Centre in Kerman, Iran. All neonates with high serum blood urea and creatinine were included in the study. The percentage of weight loss, breast feeding, mode of delivery, and clinical presentations were recorded. Laboratory tests such as blood urea, serum and urine sodium and creatinine and, urine specific gravity were done. Data were analyzed by SPSS software, chi- square test and t- test. Results: Among 36 neonates, who were eligible for the study, 29 cases (80%) had dehydration (group I) and 7 cases (20%) had intrinsic renal failure (group II). In the first group, mean weight loss was 14% and mean age at admission was 10 days. Reasons for admission were poor feeding (69%), lethargy (58%), fever (30%), jaundice, vomiting and seizure. The mode of delivery in 69% of cases were vaginal route and 82% of cases were breast-fed. Decreased urine frequency in the previous day (<6 times per day) was considered more significant than decreased stool frequency (< 3 times per day). Serum sodium and urine specific gravity in group I was significantly higher than group II (P< 0.05). Conclusion: This study confirms that an excessive weight loss over the first few days of life and decreased urine and stool frequency might be considered as a warning for failure of receiving enough milk. Serum sodium and urine specific gravity are the most sensitive laboratory parameters, for the assessment of dehydration. Keywords: Acute renal failure, Newborn infant, Dehydration, Azotemia, Breastfeedin