Extreme weather caused by concurrent cyclone, front and thunderstorm occurrences

This is the final version of the article. Available from Springer Nature via the DOI in this recordPhenomena such as cyclones, fronts and thunderstorms can cause extreme weather in various regions throughout the world. Although these phenomena have been examined in numerous studies, they have not all been systematically examined in combination with each other, including in relation to extreme precipitation and extreme winds throughout the world. Consequently, the combined influence of these phenomena represents a substantial gap in the current understanding of the causes of extreme weather events. Here we present a systematic analysis of cyclones, fronts and thunderstorms in combination with each other, as represented by seven different types of storm combinations. Our results highlight the storm combinations that most frequently cause extreme weather in various regions of the world. The highest risk of extreme precipitation and extreme wind speeds is found to be associated with a triple storm type characterized by concurrent cyclone, front and thunderstorm occurrences. Our findings reveal new insight on the relationships between cyclones, fronts and thunderstorms and clearly demonstrate the importance of concurrent phenomena in causing extreme weather.This project is supported through funding from the Australian Government’s National Environmental Science Programme (NESP)

An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

Background: Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. Methods: We investigated urinary samples (n ¼ 121) from patients with bladder cancer (n ¼ 68) and age-matched controls (n ¼ 53). Fifteen miRs were quantified using real-time PCR. Results: We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs 15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA Po0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance). Conclusion: The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed

The future of midlatitude cyclones

This is the final version. Available from the publisher via the DOI in this record.Purpose of Review This review brings together recent research on the structure, characteristics, dynamics, and impacts of extratropical cyclones in the future. It draws on research using idealized models and complex climate simulations, to evaluate what is known and unknown about these future changes. Recent Findings There are interacting processes that contribute to the uncertainties in future extratropical cyclone changes, e.g., changes in the horizontal and vertical structure of the atmosphere and increasing moisture content due to rising temperatures. Summary While precipitation intensity will most likely increase, along with associated increased latent heating, it is unclear to what extent and for which particular climate conditions this will feedback to increase the intensity of the cyclones. Future research could focus on bridging the gap between idealized models and complex climate models, as well as better understanding of the regional impacts of future changes in extratropical cyclones.Natural Environment Research Council (NERC

Factor XIII A-Subunit V34L Variant Affects Thrombus Cross-Linking in a Murine Model of Thrombosis

Objective-Factor XIII (FXIII) cross-links fibrin upon activation by thrombin. Activation involves cleavage at residue 37 by thrombin, releasing an activation peptide. A common polymorphism (valine to leucine variant at residue 34, V34L), located in the activation peptide, has been associated with increased activation rates and paradoxically a protective effect in cardiovascular disease. There is, currently, no data available on the effects of V34L from in vivo models of thrombosis. We examined the effect of FXIII V34L on clot formation and cross-linking in vivo. Approach and Results-We generated a panel of full-length recombinant human FXIII-A2 variants with amino acid substitutions in the activation peptide to investigate the effect of these variants on activation rate, and we used wild-type, V34L, and alanine to glycine variant at residue 33 variants to study the effects of varying FXIII activation rate on thrombus formation in a murine model of FeCl3 injury. FXIII activation assay showed that residues 29, 30, 33, and 34 play a critical role in thrombin interaction. Full-length recombinant human FXIII-A2 V34L has significant effects on clot formation, structure, and lysis in vitro, using turbidity assay. This variant influenced fibrin cross-linking but not size of the thrombus in vivo. Conclusions-Mutations in the activation peptide of full-length recombinant FXIII regulate activation rates by thrombin, and V34L influences in vivo thrombus formation by increased cross-linking of the clot

The contributions of fronts, lows and thunderstorms to southern Australian rainfall

This is the final version. Available from the publisher via the DOI in this record.The correction to this article is available in ORE at http://hdl.handle.net/10871/126081A systematic analysis of the main weather types influencing southern Australian rainfall is presented for the period 1979–2015. This incorporates two multi-method datasets of cold fronts and low pressure systems, which indicate the more robust fronts and lows as distinguished from the weaker and less impactful events that are often indicated only by a single method. The front and low pressure system datasets are then combined with a dataset of environmental conditions associated with thunderstorms, as well as datasets of warm fronts and high pressure systems. The results demonstrate that these weather types collectively account for about 86% of days and more than 98% of rainfall in Australia south of 25° S. We also show how the key rain-bearing weather systems vary throughout the year and for different regions, with the co-occurrence of simultaneous lows, fronts and thunderstorm conditions particularly important during the spring and summer months in southeast Australia

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

The Ischemic Stroke Genetics Study (ISGS) Protocol

BACKGROUND: The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. DISCUSSION: The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes

Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and nondiabetic subjects: the Hoorn Study.

Background: Hyperhomocysteinaemia may constitute an independent risk factor for cardiovascular disease, but it is still unclear by which pathophysiological mechanisms homocysteine (tHcy) may promote atherothrombosis. The aim of this study was firstly to examine whether tHcy is associated with endothelial dysfunction, increased adherence of leukocytes, and/or chronic low-grade inflammation, as estimated from plasma levels of von Willebrand factor (vWf), soluble vascular cell adhesion molecule 1 (sVCAM-1) and C-reactive protein (CRP), respectively. Secondly we investigated whether the presence of type 2 diabetes modifies these associations. Materials and Methods: Six hundred and ten subjects of a general population of middle-aged and elderly subjects, 170 of whom had type 2 diabetes, participated in this cross-sectional study. Linear regression analyses were used to study whether tHcy was associated with vWf, sVCAM-1 and CRP, and whether the presence of diabetes modified these associations. Results: After adjustment for confounders, tHcy was significantly but weakly associated with vWf (β=0·15, P=0·05) and sVCAM-1 (β=0·082, P=0·04). tHcy was not significantly associated with CRP (β=0·02, P=0·91). The presence of diabetes did not significantly modify these associations. Conclusions: This study provides evidence that tHcy is, at most, weakly associated with endothelial dysfunction as estimated from plasma vWf, and with leukocyte adhesion as estimated from plasma sVCAM-1. tHcy was not significantly associated with chronic low-grade inflammation as estimated from plasma CRP. Our data thus suggest that the link between tHcy and atherothrombosis cannot be explained by associations of tHcy with vWf, sVCAM-1 or CRP

Health-related quality of life after treatment for bladder cancer in England

Background Little is known about quality of life after bladder cancer treatment. This common cancer is managed using treatments that can affect urinary, sexual and bowel function. Methods To understand quality of life and inform future care, the Department of Health (England) surveyed adults surviving bladder cancer 1–5 years after diagnosis. Questions related to disease status, co-existing conditions, generic health (EQ-5D), cancer-generic (Social Difficulties Inventory) and cancer-specific outcomes (Functional Assessment of Cancer Therapy—Bladder). Results In total, 673 (54%) patients responded; including 500 (74%) men and 539 (80%) with co-existing conditions. Most respondents received endoscopic treatment (60%), while 92 (14%) and 99 (15%) received radical cystectomy or radiotherapy, respectively. Questionnaire completion rates varied (51–97%). Treatment groups reported ≥1 problem using EQ-5D generic domains (59–74%). Usual activities was the most common concern. Urinary frequency was common after endoscopy (34–37%) and radiotherapy (44–50%). Certain populations were more likely to report generic, cancer-generic and cancer-specific problems; notably those with co-existing long-term conditions and those treated with radiotherapy. Conclusion The study demonstrates the importance of assessing patient-reported outcomes in this population. There is a need for larger, more in-depth studies to fully understand the challenges patients with bladder cancer face