Microclima: An R package for modelling meso- and microclimate

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this record1.Climate is of fundamental importance to the ecology and evolution of all organisms. However, studies of climate–organism interactions usually rely on climate variables interpolated from widely‐spaced measurements or modelled at coarse resolution, whereas the conditions experienced by many organisms vary over scales from millimetres to metres. 2.To help bridge this mismatch in scale, we present models of the mechanistic processes that govern fine‐scale variation in near‐ground air temperature. The models are flexible (enabling application to a wide variety of locations and contexts), can be run using freely available data and are provided as an R package. 3.We apply a mesoclimate to the Lizard Peninsula in Cornwall to provide hourly estimates of air temperature at resolution of 100m for the period Jan‐Dec 2010. A microclimate model is then applied to a one km2 region of the Lizard Peninsula, Caerthillean Valley (49.969 ºN, 5.215 ºW), to provide hourly estimates of near‐ground air temperature at resolution of one m2 during May 2010. 4.Our models reveal substantial spatial variation in near‐ground temperatures, driven principally by variation in topography and, at the microscale, by vegetation structure. At the meso‐scale, hours of exposure to air temperatures at one m height in excess of 25 °C ranged from 23 to 158 hours, despite this temperature never being recorded by the weather station within the study area during the study period. At the micro‐scale, steep south‐facing slopes with minimal vegetation cover experienced temperatures in excess of 40 °C. 5.The microclima package is flexible and efficient and provides an accurate means of modelling fine‐scale variation in temperature. We also provide functions that facilitate users to obtain and process a variety of freely available datasets needed to drive the model.This research was part-funded by the European Social Fund Project 09099NCO5 and NERC NE/P016790/

Climate change and crop exposure to adverse weather: changes to frost risk and grapevine flowering conditions

Open Access Article© 2015 Mosedale et al.The cultivation of grapevines in the UK and many other cool climate regions is expected to benefit from the higher growing season temperatures predicted under future climate scenarios. Yet the effects of climate change on the risk of adverse weather conditions or events at key stages of crop development are not always captured by aggregated measures of seasonal or yearly climates, or by downscaling techniques that assume climate variability will remain unchanged under future scenarios. Using fine resolution projections of future climate scenarios for south-west England and grapevine phenology models we explore how risks to cool-climate vineyard harvests vary under future climate conditions. Results indicate that the risk of adverse conditions during flowering declines under all future climate scenarios. In contrast, the risk of late spring frosts increases under many future climate projections due to advancement in the timing of budbreak. Estimates of frost risk, however, were highly sensitive to the choice of phenology model, and future frost exposure declined when budbreak was calculated using models that included a winter chill requirement for dormancy break. The lack of robust phenological models is a major source of uncertainty concerning the impacts of future climate change on the development of cool-climate viticulture in historically marginal climatic regions.European Social FundNatural Environment Research Council (NERC

Extraction of ellagitannins from oak wood of model casks

Eight experimental model casks were constructed using wood from four oak trees and filled with a 12 % ethanol solution for 200 days. The concentration of ellagitannins was subsequently measured in the solutions and in the inner and outer faces of the cask wood. Only a low proportion of the total ellagitannins was extracted from the wood, and this proportion varied significantly between both different casks and between the eight ellagitannins measured. The two most abundant ellagitannins, castalagin and vescalagin, were the least easily extracted. The concentration of ellagitannins was much lower in the solutions than expected from calculations based on the difference between the inner and outer faces of the wood. This degradation of ellagitannins occurs subsequent to their extraction into solution

Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach

Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains. Genetic mapping coupled with transcriptomic analysis in the liver was used to identify several candidate susceptibility genes including epoxide hydrolase 2, interferon regulatory factor 3, and mitochondrial fission factor. Gene pathway analysis revealed that oxidative stress and immune response pathways were activated in response to tolvaptan treatment across all strains, but genes involved in regulation of bile acid homeostasis were most associated with tolvaptan-induced elevations in ALT. Secretory leukocyte peptidase inhibitor (Slpi) mRNA was also induced in the susceptible strains and was associated with increased plasma levels of Slpi protein, suggesting a potential serum marker for DILI susceptibility. In summary, tolvaptan induced signs of oxidative stress, mitochondrial dysfunction, and innate immune response in all strains, but variation in bile acid homeostasis was most associated with susceptibility to the liver response. This CC study has indicated potential mechanisms underlying tolvaptan DILI and biomarkers of susceptibility that may be useful in managing the risk of DILI in ADPKD patients

NMR metabolomics reveals effects of Cryptosporidium infections on host cell metabolome

Background: Cryptosporidium is an important gut microbe whose contributions towards infant and immunocompromise patient mortality rates are steadily increasing. Over the last decade, we have seen the development of various tools and methods for studying Cryptosporidium infection and its interactions with their hosts. One area that is sorely overlooked is the effect infection has on host metabolic processes. Results: Using a 1H nuclear magnetic resonance approach to metabolomics, we have explored the nature of the mouse gut metabolome as well as providing the first insight into the metabolome of an infected cell line. Statistical analysis and predictive modelling demonstrated new understandings of the effects of a Cryptosporidium infection, while verifying the presence of known metabolic changes. Of note is the potential contribution of host derived taurine to the diarrhoeal aspects of the disease previously attributed to a solely parasite-based alteration of the gut environment, in addition to other metabolites involved with host cell catabolism. Conclusion: This approach will spearhead our understanding of the Cryptosporidium-host metabolic exchange and provide novel targets for tackling this deadly parasite

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD). No liver injury has been observed with tolvaptan treatment in healthy subjects and in non-ADPKD indications, but ADPKD clinical trials showed evidence of drug-induced liver injury (DILI). Although all DILI events resolved, additional monitoring in tolvaptan-treated ADPKD patients is required. In vitro assays identified alterations in bile acid disposition and inhibition of mitochondrial respiration as potential mechanisms underlying tolvaptan hepatotoxicity. This report details the application of DILIsym software to determine whether these mechanisms could account for the liver safety profile of tolvaptan observed in ADPKD clinical trials. DILIsym simulations included physiologically based pharmacokinetic estimates of hepatic exposure for tolvaptan and2 metabolites, and their effects on hepatocyte bile acid transporters and mitochondrial respiration. The frequency of predicted alanine aminotransferase (ALT) elevations, following simulated 90/30 mg split daily dosing, was 7.9% compared with clinical observations of 4.4% in ADPKD trials. Toxicity was multifactorial as inhibition of bile acid transporters and mitochondrial respiration contributed to the simulated DILI. Furthermore, simulation analysis identified both pre-treatment risk factors and on-treatment biomarkers predictive of simulated DILI. The simulations demonstrated that in vivo hepatic exposure to tolvaptan and the DM-4103 metabolite, combined with these 2 mechanisms of toxicity, were sufficient to account for the initiation of tolvaptan-mediated DILI. Identification of putative risk-factors and potential novel biomarkers provided insight for the development of mechanism-based tolvaptan risk-mitigation strategies

Urinary tract infections and antibiotic use in pregnancy - qualitative analysis of online forum content

Background Antibiotics are standard treatment for asymptomatic and symptomatic urinary tract infections (UTIs) in pregnancy. Their overuse, however, can contribute to antimicrobial resistance (AMR) and expose the foetus to drugs that might affect its development. Preventative behaviours are currently the best option to reduce incidences of UTIs and to avoid the use of antibiotics in pregnancy. The aim of this study was to explore women’s experiences of UTIs in pregnancy to develop an understanding of their concerns and to optimise and encourage behaviours that facilitate appropriate use of antibiotics. Methods An online pregnancy forum in the United Kingdom (UK) was used to collect data on women’s discussions of UTIs. A total of 202 individual threads generated by 675 different usernames were selected for analysis. The data was organised using NVivo 11® software and then analysed qualitatively using inductive thematic analysis. Results Women’s perceptions of UTIs and antibiotic use in pregnancy were driven by their pre-natal attachment to the foetus. UTIs were thought to be common and high risk in pregnancy, which meant that antibiotics were viewed as essential in the presence of suspected symptoms. The dominant view about antibiotics was that their use was safe and of little concern in pregnancy. Women reported an emotional reaction to developing a UTI. They coped by seeking information about behaviour change strategies to assist with recovery and through emotional support from the online forum. Conclusions Women face dual risks when they experience UTIs; the risk from the infection and the risk from antibiotic treatment. Pre-natal attachment to the foetus is highlighted in the decision making process. The focus is on the shorter term risk from UTIs while undermining the longer term risks from antibiotic use, especially the risk of AMR. A balanced view needs to be presented, and evidence-based infection prevention strategies should be promoted, to women to ensure appropriate antibiotic use in pregnancy, to address the global challenge of AMR

Divided we stand: institutional collaboration in tourism planning and development in the Central Region of Ghana

This research is an exploratory study that examines collaboration at the institutional level in the tourism sector of the Central Region, Ghana. The research begins with a review of the key issues related to collaboration in tourism planning and development followed by an extensive exploration of three main issues related to institutional collaboration in tourism in the Central Region. The three main issues are the vision of tourism development shared among stakeholders, collaboration and coordination within the public sector and between the public and private sectors and the factors that constrain and facilitate collaboration and coordination. Using extensive interviews with key stakeholders and reviewing policy documents, the research indicates low levels of collaboration between tourism institutions both within the public sector and across the public?private sectors. This is notwithstanding a shared awareness of the benefits of collaboration among all actors. The research thus contributes interesting insights into the politics of collaboration in tourism destinations. Given tourism's contribution to the Ghanaian economy, it is imperative that efforts are made towards improving the levels of collaboration and coordination between tourism agencies and institutions

Anatomy of Indian heatwaves

India suffers from major heatwaves during March-June. The rising trend of number of intense heatwaves in recent decades has been vaguely attributed to global warming. Since the heat waves have a serious effect on human mortality, root causes of these heatwaves need to be clarified. Based on the observed patterns and statistical analyses of the maximum temperature variability, we identified two types of heatwaves. The first-type of heatwave over the north-central India is found to be associated with blocking over the North Atlantic. The blocking over North Atlantic results in a cyclonic anomaly west of North Africa at upper levels. The stretching of vorticity generates a Rossby wave source of anomalous Rossby waves near the entrance of the African Jet. The resulting quasi-stationary Rossby wave-train along the Jet has a positive phase over Indian subcontinent causing anomalous sinking motion and thereby heatwave conditions over India. On the other hand, the second-type of heatwave over the coastal eastern India is found to be due to the anomalous Matsuno-Gill response to the anomalous cooling in the Pacific. The Matsuno-Gill response is such that it generates northwesterly anomalies over the landmass reducing the land-sea breeze, resulting in heatwaves