Exogenous glycosaminoglycans coat damaged bladder surfaces in experimentally damaged mouse bladder

BACKGROUND: Interstital cystitis is often treated with exogenous glycosaminoglycans such as heparin, chondroitin sulphate (Uracyst), hyaluronate (Cystistat) or the semi-synthetic pentosan polysulphate (Elmiron). The mechanism of action is presumed to be due to a coating of the bladder surface to replace the normally present chondroitin sulphate and heparan sulphate lost as a result of the disease. This study used fluorescent labelled chondroitin sulphate to track the distribution of glycosaminoglycans administered intravesically to mouse bladder that had been damaged on the surface. METHODS: The surfaces of mouse bladders were damaged by 3 mechanisms – trypsin, 10 mM HCl, and protamine sulphate. Texas Red-labeled chondroitin sulphate was instilled into the bladders of animals with damaged bladders and controls instilled only with saline. Bladders were harvested, frozen, and sectioned for examination by fluorescence. RESULTS: The normal mouse bladder bound a very thin layer of the labelled chondroitin sulphate on the luminal surface. Trypsin- and HCl-damaged bladders bound the labelled chondroitin sulphate extensively on the surface with little penetration into the bladder muscle. Protamine produced less overt damage, and much less labelling was seen, presumably due to loss of the label as it complexed with the protamine intercalated into the bladder surface. CONCLUSION: Glycosaminoglycan administered intravesically does bind to damaged bladder. Given that the changes seen following bladder damage resemble those seen naturally in interstitial cystitis, the mechanisms proposed for the action of these agents is consistent with a coating of damaged bladder

Prospects for seasonal forecasting of iceberg distributions in the North Atlantic

An efficient approach to ocean–iceberg modelling provides a means for assessing prospects for seasonal forecasting of iceberg distributions in the northwest Atlantic, where icebergs present a hazard to mariners each spring. The stand-alone surface (SAS) module that is part of the Nucleus for European Modelling of the Ocean (NEMO) is coupled with the NEMO iceberg module (ICB) in a “SAS-ICB” configuration with horizontal resolution of 0.25°. Iceberg conditions are investigated for three recent years, 2013–2015, characterized by widely varying iceberg distributions. The relative simplicity of SAS-ICB facilitates efficient investigation of sensitivity to iceberg fluxes and prevailing environmental conditions. SAS-ICB is provided with daily surface ocean analysis fields from the global Forecasting Ocean Assimilation Model (FOAM) of the Met Office. Surface currents, temperatures and height together determine iceberg advection and melting rates. Iceberg drift is further governed by surface winds, which are updated every 3 h. The flux of icebergs from the Greenland ice sheet is determined from engineering control theory and specified as an upstream flux in the vicinity of Davis Strait for January or February. Simulated iceberg distributions are evaluated alongside observations reported and archived by the International Ice Patrol. The best agreement with observations is obtained when variability in both upstream iceberg flux and oceanographic/atmospheric conditions is taken into account. Including interactive icebergs in an ocean–atmosphere model with sufficient seasonal forecast skill, and provided with accurate winter iceberg fluxes, it is concluded that seasonal forecasts of spring/summer iceberg conditions for the northwest Atlantic are now a realistic prospect

Minimal Holocene retreat of large tidewater glaciers in Køge Bugt, southeast Greenland

Abstract Køge Bugt, in southeast Greenland, hosts three of the largest glaciers of the Greenland Ice Sheet; these have been major contributors to ice loss in the last two decades. Despite its importance, the Holocene history of this area has not been investigated. We present a 9100 year sediment core record of glaciological and oceanographic changes from analysis of foraminiferal assemblages, the abundance of ice-rafted debris, and sortable silt grain size data. Results show that ice-rafted debris accumulated constantly throughout the core; this demonstrates that glaciers in Køge Bugt remained in tidewater settings throughout the last 9100 years. This observation constrains maximum Holocene glacier retreat here to less than 6 km from present-day positions. Retreat was minimal despite oceanic and climatic conditions during the early-Holocene that were at least as warm as the present-day. The limited Holocene retreat of glaciers in Køge Bugt was controlled by the subglacial topography of the area; the steeply sloping bed allowed glaciers here to stabilise during retreat. These findings underscore the need to account for individual glacier geometry when predicting future behaviour. We anticipate that glaciers in Køge Bugt will remain in stable configurations in the near-future, despite the predicted continuation of atmospheric and oceanic warming

Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology

BACKGROUND: Lack of agreement about criteria and terminology for children's language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology. METHODS: The Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities. RESULTS: We achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term ‘Language Disorder’ is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, ‘Developmental Language Disorder’ (DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co-occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability. CONCLUSIONS: This Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature

The Dual Effects of Critical Thinking Disposition on Worry

This study investigated the relationship between disposition (people’s consistent motivation) toward critical thinking (CT) and worrying. In spite of its connection to psychopathology, worry is thought to represent an effort at problem-solving. Moreover, worry has been found to be underpinned by cognitive development, leading us to predict a positive relationship between worry and CT disposition. On the other hand, cognitive behavioral therapy, which involves techniques similar to CT, has been shown to be effective in reducing worrying, suggesting that increasing CT disposition decreases worrying. This study attempted to reconcile these seemingly contrasting predictions about the relationship between CT disposition and worrying by using multiple mediator analysis. A model was proposed wherein the mediators, responsibility to continue thinking and detached awareness of negative thinking, were related to two opposing predictions. The former is thought to lead to enhanced worrying and the latter to reduced worrying, with both positively related to CT disposition. A questionnaire study with university students (N = 760) revealed that CT disposition enhanced worrying by obliging people to continue thinking about a problem, but that it also reduced worrying by enhancing the detached and objective awareness of their negative thoughts. This study thus demonstrated the dual effects of CT disposition on worrying through different mediators. Thus, when enhancing CT disposition, it is important for educators to be aware of possible disadvantages apart from its worry-reducing effect. Future studies should therefore examine the underlying mechanisms of these two effects of CT disposition