Diurnal self-aggregation

Convective self-aggregation is a modelling paradigm for thunderstorm organisation over a constant-temperature tropical sea surface. This setup can give rise to cloud clusters over timescales of weeks. In reality, sea surface temperatures do oscillate diurnally, affecting the atmospheric state. Over land, surface temperatures vary more strongly, and rain rate is significantly influenced. Here, we carry out a substantial suite of cloud-resolving numerical experiments, and find that even weak surface temperature oscillations enable qualitatively different dynamics to emerge: the spatial distribution of rainfall is only homogeneous during the first day. Already on the second day, the rain field is firmly structured. In later days, the clustering becomes stronger and alternates from day-to-day. We show that these features are robust to changes in resolution, domain size, and surface temperature, but can be removed by a reduction of the amplitude of oscillation, suggesting a transition to a clustered state. Maximal clustering occurs at a scale of $\mathbf{l_{max}\approx 180\;km}$, a scale we relate to the emergence of mesoscale convective systems. At $\mathbf{l_{max}}$ rainfall is strongly enhanced and far exceeds the rainfall expected at random. We explain the transition to clustering using simple conceptual modelling. Our results may help clarify how continental extremes build up and how cloud clustering over the tropical ocean could emerge much faster than through conventional self-aggregation alone.Comment: 27 pages, 4 main figures, 7 supplementary figures, 2 main tables, 1 supplementary tabl

Blood glucose testing and primary prevention of diabetes mellitus type 2 - evaluation of the effect of evidence based patient information

<p>Abstract</p> <p>Background</p> <p>Evidence-based patient information (EBPI) has been recognised as important tool for informed choice in particular in the matter of preventive options. An objective, on the best scientific evidence-based consumer information about subthreshold elevated blood glucose levels (impaired fasting glucose and impaired glucose tolerance) and primary prevention of diabetes, is not available yet. Thus we developed a web-based EBPI and aim to evaluate its effects on informed decision making in people 50 years or older.</p> <p>Methods/Design</p> <p>We conduct a web-based randomised-controlled trial to evaluate the effect of information about elevated blood glucose levels and diabetes primary prevention on five specific outcomes: (i) knowledge of elevated blood glucose level-related issues (primary outcome); (ii) attitudes to a metabolic testing; (iii) intention to undergo a metabolic testing; (iv) decision conflict; (v) satisfaction with the information. The intervention group receives a specially developed EBPI about subthreshold elevated blood glucose levels and diabetes primary prevention, the control group information about this topic, available in the internet.</p> <p>The study population consists of people between 50 and 69 years of age without known diabetes. Participants will be recruited via the internet page of the cooperating health insurance company, Techniker Krankenkasse (TK), and the internet page of the German Diabetes Centre. Outcomes will be measured through online questionnaires. We expect better informed participants in the intervention group.</p> <p>Discussion</p> <p>The design of this study may be a prototype for other web-based prevention information and their evaluation.</p> <p>Trial registration</p> <p>Current Controlled Trial: ISRCTN22060616.</p

Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency

BACKGROUND & AIMS: Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. METHODS: We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7. RESULTS: In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. CONCLUSIONS: We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies