Regional methods for evaluating the effects of flow alteration on stream ecosystems

2012 Summer.Includes bibliographical references.Three stand-alone chapters explore the development and implementation of regional flow-ecology methods. Ecohydrology is an interdisciplinary field that brings together specialized research in hydrology, hydraulics, geomorphology and ecology. My dissertation reflects the need for interdisciplinary knowledge, tackling issues as diverse as low flows for trout (Chapter 2) to peak flows for cottonwood (Chapter 3). A regional-scale view unifies these investigations, with Chapter 1 establishing the scientific foundation and management objectives for regional flow-ecology methods. Summary Chapter 1 - To balance the benefits of dams and water diversions against society's expectations for the natural environment, flow managers require scientific advice on the ecosystem response to flow alteration. The methods selected to investigate the ecosystem effects of flow alteration (e.g., PHABSIM - Physical Habitat Simulation) should reflect the scale of flow management and the information requirements of flow managers. In addition, a hierarchical habitat framework provides an ecological foundation for the development and implementation of flow-ecology methods, because ecosystem response to flow is constrained by large-scale processes. This can be put into practice using hydrogeomorphic classification to define the higher-level physical processes (e.g., sediment transport, disturbance) that dictate the mechanisms of biotic response to flow. Regional flow-ecology methods provide a vehicle for incorporating prior knowledge and hydrogeomorphic processes into flow management at both regional and local scales. Chapter 2 - Changes in hydraulic habitat (depth and velocity) with flow can be predicted using intensive reach-specific methods, such as PHABSIM. I used existing PHABSIM data to develop GHMs (Generalized Habitat Models) that predict trout habitat-flow curves for unsurveyed streams of the southern Rocky Mountains. Predicted habitat was significantly correlated with the abundance of large brown trout (P40% flow reduction). Historic photographs revealed that narrowleaf in the Middle Park area (Colorado) have increased in abundance since dam closure, colonizing previously bare gravel bars. That narrowleaf appear less sensitive to flow alteration than plains cottonwood could reflect different species traits (e.g., alternative sources of disturbance for root suckering by narrowleaf), together with the many physical transitions from plains to mountains that are associated with the species transition

Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea-hypnoea index (AHI).

INTRODUCTION: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA. METHODS AND ANALYSIS: This is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea-hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA1c) ≥47 mmol/mol), will be recruited from diabetes and sleep medicine outpatient clinics in primary and secondary care settings across Liverpool. Patients will be allocated equally, using computer-generated random, permuted blocks of unequal sizes, to each of the four treatment arms for 26 weeks: (i) liraglutide (1.8 mg once per day) alone, (ii) liraglutide 1.8 mg once per day with CPAP, (iii) CPAP alone (conventional care) or (iv) no treatment (control). The primary outcome measure is change in OSA severity, determined by AHI. Secondary outcome measures include effects on glycaemic control (glycated haemoglobin (HbA1c)), body weight and quality of life measures. Exploratory measures include measures of physical activity, MRI-derived measures of regional body composition including fat mass (abdominal subcutaneous, visceral, neck and liver fat) and skeletal muscle mass (cross-sectional analysis of thigh), indices of cardiac function (using transthoracic echocardiography) and endothelial function. ETHICAL APPROVAL: The study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBERS: ISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677

Joint diffraction and modeling approach to the structure of liquid alumina

The structure of liquid alumina at a temperature ∼2400 K near its melting point was measured using neutron and high-energy x-ray diffraction by employing containerless aerodynamic–levitation and laser-heating techniques. The measured diffraction patterns were compared to those calculated from molecular dynamics simulations using a variety of pair potentials, and the model found to be in best agreement with experiments was refined using the reverse Monte Carlo method. The resultant model shows that the melt is composed predominantly of AlO4 and AlO5 units, in the approximate ratio of 2:1, with only minor fractions of AlO3 and AlO6 units. The majority of Al-O-Al connections involve corner-sharing polyhedra (83%), although a significant minority involve edge-sharing polyhedra (16%), predominantly between AlO5 and either AlO5 or AlO4 units. Most of the oxygen atoms (81%) are shared among three or more polyhedra, and the majority of these oxygen atoms are triply shared among one or two AlO4 units and two or one AlO5 units, consistent with the abundance of these polyhedra in the melt and their fairly uniform spatial distribution

The potential of trading activity income to fund third sector organisations operating in deprived areas

In the United Kingdom, as in other countries, Third Sector Organisations (TSOs) have been drawn towards income sources associated with trading activities (Teasdale, 2010), but many remain reliant on grant funding to support such activities (Chell, 2007). Using a multivariate analysis approach and data from the National Survey of Charities and Social Enterprises (NSCSE), it is found that trading activities are used relatively commonly in deprived areas. These organisations are also more likely to attempt to access public sector funds. This suggests policy-makers need to consider the impact of funding cuts on TSOs in the most deprived areas as TSOs are unlikely achieve their objectives without continuing support

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes A Prespecified Secondary Analysis of a Randomized Clinical Trial

ImportanceSodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown.ObjectiveTo assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).Design, setting, and participantsThis secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (InterventionsDapagliflozin vs placebo.Main outcomes and measuresThe dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF.ResultsAt baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher.Conclusions and relevanceThe effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria.Trial registrationClinicalTrials.gov Identifier: NCT01730534

What’s missing from legal geography and materialist studies of law? Absence and the assembling of asylum appeal hearings in Europe

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: Due to the ethical and legally sensitive nature of the research, ethnographic notes taken in court could not be made openly available. Appellant interviewees were not asked for their permission to share their interview transcripts in an online open archive because of concerns that they could misunderstand what was being asked for, or feel obliged to agree but subsequently feel less able to conduct free conversation in research interviews as a result, thereby negatively impacting on the quality of the data generated. Additional details relating to, and data resulting from, to a survey taken during observations of British asylum appeals between 2013 and 2016 are available from the UK Data Archive (persistent identifier: 10.5255/UKDA-SN-852032).There is an absence of absence in legal geography and materialist studies of the law. Drawing on a multi‐sited ethnography of European asylum appeal hearings, this paper illustrates the importance of absences for a fully‐fledged materiality of legal events. We show how absent materials impact hearings, that non‐attending participants profoundly influence them, and that even when participants are physically present, they are often simultaneously absent in other, psychological registers. In so doing we demonstrate the importance and productivity of thinking not only about law's omnipresence but also the absences that shape the way law is experienced and practiced. We show that attending to the distribution of absence and presence at legal hearings is a way to critically engage with legal performance.Economic and Social Research Council (ESRC)European Research Council (ERC

The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58

OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk. RESEARCH DESIGN AND METHODS DECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance >60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (15 to = 30 to 300 mg/g) by treatment arm. The composite cardiorenal outcome was a >= 40% sustained decline in the estimated glomerular filtration rate (eGFR) to 15 to 300 mg/g. Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories (all P = 1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 1.45 [95% CI 1.35-1.56], P = 30 mg/g (P < 0.0125, P-interaction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P < 0.05, P-interaction = 0.480). CONCLUSIONS In DECLARE-TIMI 58, dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease

Interactive Marine Spatial Planning: Siting Tidal Energy Arrays around the Mull of Kintyre

The rapid development of the offshore renewable energy sector has led to an increased requirement for Marine Spatial Planning (MSP) and, increasingly, this is carried out in the context of the ‘ecosystem approach’ (EA) to management. We demonstrate a novel method to facilitate implementation of the EA. Using a real-time interactive mapping device (touch-table) and stakeholder workshops we gathered data and facilitated negotiation of spatial trade-offs at a potential site for tidal renewable energy off the Mull of Kintyre (Scotland). Conflicts between the interests of tidal energy developers and commercial and recreational users of the area were identified, and use preferences and concerns of stakeholders were highlighted. Social, cultural and spatial issues associated with conversion of common pool to private resource were also revealed. The method identified important gaps in existing spatial data and helped to fill these through interactive user inputs. The workshops developed a degree of consensus between conflicting users on the best areas for potential development suggesting that this approach should be adopted during MSP

Deciphering mollusc shell production: the roles of genetic mechanisms through to ecology, aquaculture and biomimetics

Most molluscs possess shells, constructed from a vast array of microstructures and architectures. The fully formed shell is composed of calcite or aragonite. These CaCO3 crystals form complex biocomposites with proteins, which although typically less than 5% of total shell mass, play significant roles in determining shell microstructure. Despite much research effort, large knowledge gaps remain in how molluscs construct and maintain their shells, and how they produce such a great diversity of forms. Here we synthesize results on how shell shape, microstructure, composition and organic content vary among, and within, species in response to numerous biotic and abiotic factors. At the local level, temperature, food supply and predation cues significantly affect shell morphology, whilst salinity has a much stronger influence across latitudes. Moreover, we emphasize how advances in genomic technologies [e.g. restriction site-associated DNA sequencing (RAD-Seq) and epigenetics] allow detailed examinations of whether morphological changes result from phenotypic plasticity or genetic adaptation, or a combination of these. RAD-Seq has already identified single nucleotide polymorphisms associated with temperature and aquaculture practices, whilst epigenetic processes have been shown significantly to modify shell construction to local conditions in, for example, Antarctica and New Zealand. We also synthesize results on the costs of shell construction and explore how these affect energetic trade-offs in animal metabolism. The cellular costs are still debated, with CaCO3 precipitation estimates ranging from 1-2 J/mg to 17-55 J/mg depending on experimental and environmental conditions. However, organic components are more expensive (~29 J/mg) and recent data indicate transmembrane calcium ion transporters can involve considerable costs. This review emphasizes the role that molecular analyses have played in demonstrating multiple evolutionary origins of biomineralization genes. Although these are characterized by lineage-specific proteins and unique combinations of co-opted genes, a small set of protein domains have been identified as a conserved biomineralization tool box. We further highlight the use of sequence data sets in providing candidate genes for in situ localization and protein function studies. The former has elucidated gene expression modularity in mantle tissue, improving understanding of the diversity of shell morphology synthesis. RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats - CRISPR-associated protein 9 (CRISPR-Cas9) experiments have provided proof of concept for use in the functional investigation of mollusc gene sequences, showing for example that Pif (aragonite-binding) protein plays a significant role in structured nacre crystal growth and that the Lsdia1 gene sets shell chirality in Lymnaea stagnalis. Much research has focused on the impacts of ocean acidification on molluscs. Initial studies were predominantly pessimistic for future molluscan biodiversity. However, more sophisticated experiments incorporating selective breeding and multiple generations are identifying subtle effects and that variability within mollusc genomes has potential for adaption to future conditions. Furthermore, we highlight recent historical studies based on museum collections that demonstrate a greater resilience of molluscs to climate change compared with experimental data. The future of mollusc research lies not solely with ecological investigations into biodiversity, and this review synthesizes knowledge across disciplines to understand biomineralization. It spans research ranging from evolution and development, through predictions of biodiversity prospects and future-proofing of aquaculture to identifying new biomimetic opportunities and societal benefits from recycling shell products.FCT: UID/Multi/04326/2019; European Marine Biological Research Infrastructure Cluster-EMBRIC (EU H2020 research and innovation program) 654008; European Union Seventh Framework Programme [FP7] ITN project 'CACHE: Calcium in a Changing Environment' under REA 60505; NERC Natural Environment Research Council NE/J500173/1info:eu-repo/semantics/publishedVersio

Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis

In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated.We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development.This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function