Cell viscoelasticity is linked to fluctuations in cell biomass distributions.

The viscoelastic properties of mammalian cells can vary with biological state, such as during the epithelial-to-mesenchymal (EMT) transition in cancer, and therefore may serve as a useful physical biomarker. To characterize stiffness, conventional techniques use cell contact or invasive probes and as a result are low throughput, labor intensive, and limited by probe placement. Here, we show that measurements of biomass fluctuations in cells using quantitative phase imaging (QPI) provides a probe-free, contact-free method for quantifying changes in cell viscoelasticity. In particular, QPI measurements reveal a characteristic underdamped response of changes in cell biomass distributions versus time. The effective stiffness and viscosity values extracted from these oscillations in cell biomass distributions correlate with effective cell stiffness and viscosity measured by atomic force microscopy (AFM). This result is consistent for multiple cell lines with varying degrees of cytoskeleton disruption and during the EMT. Overall, our study demonstrates that QPI can reproducibly quantify cell viscoelasticity

Quantum Films Adsorbed on Graphite: Third and Fourth Helium Layers

Using a path-integral Monte Carlo method for simulating superfluid quantum films, we investigate helium layers adsorbed on a substrate consisting of graphite plus two solid helium layers. Our results for the promotion densities and the dependence of the superfluid density on coverage are in agreement with experiment. We can also explain certain features of the measured heat capacity as a function of temperature and coverage.Comment: 13 pages in the Phys. Rev. two-column format, 16 Figure

A proposition for the diagnosis and treatment of gastro-oesophageal reflux disease in children: A report from a working group on gastro-oesophageal reflux disease

In this paper, a Working Group on Gastro-Oesophageal Reflux discusses recommendations for the first line diagnostic and therapeutic approach of gastro-oesophageal reflux disease in infants and children. All members of the Working Group agreed that infants with uncomplicated gastro-oesophageal reflux can be safely treated before performing (expensive and often unnecessary) complementary investigations. However, the latter are mandatory if symptoms persist despite appropriate treatment. Oesophageal pH monitoring of long duration (18-24 h) is recommended as the investigation technique of choice in infants and children with atypical presentations of gastro-oesophageal reflux. Upper gastro-intestinal endoscopy in a specialised centre is the technique of choice in infants and children presenting with symptoms suggestive of peptic oesophagitis. Prokinetics, still a relatively new drug family, have already obtained a definitive place in the treatment of gastro-oesophageal reflux disease in infants and children, especially if "non-drug" treatment (positional therapy, dietary recommendations, etc.) was unsuccessful. It was the aim of the Working Group to help the paediatrician with this consensus statement and guide-lines to establish a standardised management of gastro-oesophageal reflux disease in infants and children

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Setting international standards for patient and parent involvement and engagement in childhood, adolescent and young adult cancer research: A report from a European Collaborative Workshop

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) in research, advocates for research conducted ‘with’ not ‘for’ the affected population. In paediatric oncology research, the parents of children, adolescents and young adults affected by cancer are represented by the term ‘public’ in the acronym PPIE. Patients (those with cancer and cancer survivors) are also passionate advocates who drive forward the research priorities of children, adolescents and young adults throughout the entire research process. AIMS: A workshop was held at an international professional meeting in 2019 with the aim to define Patient and Parent Involvement and Engagement (PPIE); capture PPIE activities on a European level; and to explore the role of PPIE in non-interventional research. A proposed framework for a European PPIE strategy for childhood, adolescent and young adult cancers was also discussed. METHODS: The 60-minute workshop was attended by health care professionals, researchers, scientists, parents, survivors and charity/support organisations. A presentation to define PPIE, including the difference in terminology for PPIE in the context of childhood, adolescent, and young adult cancers was discussed. Best practice examples from the United Kingdom (UK) helped to demonstrate the positive impact of PPIE in paediatric oncology research. Three breakout groups then explored themes relating to PPIE, namely PPIE priorities, PPIE mapping for Europe, and PPIE in non-interventional research and data-linkage. RESULTS: Disparity in PPIE activities across Europe was evident, with ambiguity surrounding terminology and expected roles for PPIE representatives in paediatric oncology research. A lack of PPIE activity in Eastern Europe correlated with a lack of availability for clinical trials and poorer survival rates for paediatric oncology patients. There was unanimous support for PPIE embedded research in all areas, including in non-interventional studies. CONCLUSION: A European-level definition of PPIE for paediatric oncology research is needed. Further exploration into the role and responsibilities of patients, parents, and professionals when undertaking PPIE related activities is also recommended. Best practice examples from the UK, France, Germany, The Netherlands and Belgium demonstrated a preliminary evidence base from which a European PPIE strategy framework can be designed, inclusive of the patient and parent voice

The ACER pollen and charcoal database: A global resource to document vegetation and fire response to abrupt climate changes during the last glacial period

This is the final version of the article. Available from Copernicus Publications via the DOI in this record.Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard-Oeschger (D-O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D-O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73-15ka) with a temporal resolution better than 1000years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (14C, 234U/230Th, optically stimulated luminescence (OSL), 40Ar/39Ar-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft Access™ at https://doi.org/10.1594/PANGAEA.870867.The members of the ACER project wish to thank the QUEST-DESIRE (UK and France) bilateral project, the INQUA International Focus Group ACER and the INTIMATE-COST action for funding a suite of workshops to compile the ACER pollen and charcoal database and the workshop on ACER chronology that allow setting the basis for harmonizing the chronologies. Josué M. Polanco-Martinez was funded by a Basque Government postdoctoral fellowship (POS_2015_1_0006) and Sandy P. Harrison by the ERC Advanced Grant GC2.0: unlocking the past for a clearer future