Characteristics of stable flows over Southern Greenland

The main characteristic features of stable atmospheric flows over a large mountain plateau are summarised and then compared with mesoscale and synoptic scale numerical simulation, meteorological analysis, satellite imagery, and surface observations for the cases of flows over Southern Greenland for four wind directions. The detailed features are identified using the concepts and scaling of stably stratified flow over large mountains with variations in surface roughness, elevation, and heating. For westerly and easterly winds detached jets form at the southern tip, where coastal jets converge, which propagate large distances across the ocean. Near coasts katabatic winds can combine with barrier jets and wake flows generated by synoptic winds. Note how the approach flow rises/falls over southern Greenland for easterly/westerly winds, leading in both cases to more cloud on the western side. Some conclusions are drawn about the large-scale influences of these flows; detached jets in the atmosphere; air-sea interaction; formation of low pressure systems. For accurate simulations of these flows, mesoscale models are necessary with resolutions of order of 20 km or less. © Birkhäuser Verlag, Basel, 2005

Evaluating future risk of NAFLD in adolescents:a prediction and decision curve analysis

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex. METHODS: Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed “routine clinical measures”. Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1. RESULTS: The “routine clinical measures” model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The “routine clinical measures” model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents’ assumption, was the “routine clinical measures” model. However, the net benefit was marginal (0.0054 [0.0034–0.0075]). CONCLUSION: In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-022-02401-y

Knowledge practices in design: The role of visual representations as 'epistemic objects'

We use a detailed study of the knowledge work around visual representations to draw attention to the multidimensional nature of `objects'. Objects are variously described in the literatures as relatively stable or in flux; as abstract or concrete; and as used within or across practices. We clarify these dimensions, drawing on and extending the literature on boundary objects, and connecting it with work on epistemic and technical objects. In particular, we highlight the epistemic role of objects, using our observations of knowledge work on an architectural design project to show how, in this setting, visual representations are characterized by a `lack' or incompleteness that precipitates unfolding. The conceptual design of a building involves a wide range of technical, social and aesthetic forms of knowledge that need to be developed and aligned. We explore how visual representations are used, and how these are meaningful to different stakeholders, eliciting their distinct contributions. As the project evolves and the drawings change, new issues and needs for knowledge work arise. These objects have an `unfolding ontology' and are constantly in flux, rather than fully formed. We discuss the implications for wider understandings of objects in organizations and for how knowledge work is achieved in practice

Zooming in and out : studying practices by switching theoretical lenses and trailing connections

This paper contributes to re-specifying a number of the phenomena of interest to organisational studies in terms of patterns of socio-material practices and their effects. It does so by outlining a vocabulary and strategy that make up a framework for theorising work and organisational practices. The vocabulary is based on number of sensitising concepts that connote practice as an open-ended, heterogeneous accomplishment which takes place within a specific horizon of sense and a set of concerns which the practice itself brings to bear. The strategy is based on the metaphorical movement of "zooming in" and "zooming out of" practice. The zooming in and out are obtained through switching theoretical lenses and repositioning in the field, so that certain aspects of the practice are fore-grounded while others are bracketed. Building on the results of an extended study of telemedicine, the paper discusses in detail the different elements of the framework and how it enhances our capacity to re-present practice. The paper concludes with some considerations on how the proposed approach can assist us in advancing the research agenda of organizational and work studies

Representational predicaments at three Hong Kong sites

Representational predicaments arise when a job incumbent believes that attributions and images assumed by dominant authorities unfavourably ignore, or disproportionately and unfavourably emphasize, aspects of the incumbent\u27s own work and social identity. This is likely to happen when the incumbent does not have a close relationship with a dominant authority, and when power asymmetries give the former relatively little control over which aspects of their work and social identity are made visible or invisible to the latter. We draw on critical incident interviews from three organizations to illustrate a typology of six types of representational predicament: invasive spotlighting, idiosyncratic spotlighting, embedded background work, paradoxical social visibility, standardization of work processes, and standardization of work outputs. We analyse responses to representational predicaments according to whether they entailed exit, voice, loyalty, or neglect. Incumbents tended to respond with loyalty if they felt able and willing to accommodate their work behaviour and/or social identity to the dominant representations, and if there were sufficient compensatory factors, such as intrinsic rewards from the work or solidarity with colleagues. Exit or neglect appeared to reflect the belief that it was impossible to accommodate. Power asymmetries appeared to deter voice. Individual employees with a close and cordial working relationship with a member of a dominant authority group, or who were relationally networked to one, appeared not to experience representational predicaments

Validation of loci at 2q14.2 and 15q21.3 as risk factors for testicular cancer.

Testicular germ cell tumor (TGCT), the most common cancer in men aged 18 to 45 years, has a strong heritable basis. Genome-wide association studies (GWAS) have proposed single nucleotide polymorphisms (SNPs) at a number of loci influencing TGCT risk. To further evaluate the association of recently proposed risk SNPs with TGCT at 2q14.2, 3q26.2, 7q36.3, 10q26.13 and 15q21.3, we analyzed genotype data on 3,206 cases and 7,422 controls. Our analysis provides independent replication of the associations for risk SNPs at 2q14.2 (rs2713206 at P = 3.03 × 10-2; P-meta = 3.92 × 10-8; nearest gene, TFCP2L1) and rs12912292 at 15q21.3 (P = 7.96 × 10-11; P-meta = 1.55 × 10-19; nearest gene PRTG). Case-only analyses did not reveal specific associations with TGCT histology. TFCP2L1 joins the growing list of genes located within TGCT risk loci with biologically plausible roles in developmental transcriptional regulation, further highlighting the importance of this phenomenon in TGCT oncogenesis

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

Cytochrome P450 Allele CYP3A7*1C Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer.

CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7*1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P = 0.03), all-cause mortality in lung cancer patients (HR, 1.43; P = 0.009), and CLL progression (HR, 1.62; P = 0.03). We also found borderline evidence of a statistical interaction between the CYP3A7*1C allele, treatment of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (Pinteraction = 0.06). The CYP3A7*1C allele, which results in adult expression of the fetal CYP3A7 gene, is likely to be the functional allele influencing levels of circulating endogenous sex hormones and outcome in these various malignancies. Further studies confirming these associations and determining the mechanism by which CYP3A7*1C influences outcome are required. One possibility is that standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximately 8% of cancer patients who are CYP3A7*1C carriers