Predicting the ecological impacts of a new freshwater invader:Functional responses and prey selectivity of the 'killer shrimp', Dikerogammarus villosus, compared to the native Gammarus pulex

The ability to predict the likely ecological impacts of invasive species in fresh waters is a pressing research requirement. Whilst comparisons of species traits and considerations of invasion history have some efficacy in this respect, we require robust methods that can compare the effects of native and invasive species. Here, we utilise comparative functional responses and prey selectivity experiments to understand and predict the ecological impact of an invader as compared to a native. We compared the predatory functional responses of an emerging invasive species in Europe, the 'killer shrimp', Dikerogammarus villosus, and an analogous native species, Gammarus pulex, towards three representative prey species: Asellus aquaticus, Daphnia magna and Chironomus sp. Furthermore, as ecological impact may be greater for invasive species with more indiscriminate feeding habits, we compared the selectivity for the three prey types between the invasive and native species. In both the presence and absence of experimental habitats, large D. villosus, and those matched for body size with G. pulex, generally showed higher (Type II) functional responses than G. pulex, with the invasive species exhibiting higher maximum feeding rates. Further, D. villosus exhibited significantly more indiscriminate prey selection compared with G. pulex, a trait that became more evident as the invader increased in size. Differences in functional responses and prey selectivity were prey species specific, with higher to lower predicted impacts in the order A. aquaticus, D. magna and Chironomus sp. This is in accord with the impact of this invasive species on macroinvertebrates in the field. We thus provide understanding of the known ecological impact of D. villosus and discuss the utility of the phenomenological use of comparative functional responses and resource use as a tool through which the potential ecological impacts of invasive species may be identified. © 2013 John Wiley & Sons Ltd.

Lessons from 'The Wire': Epistemological Reflections on the Practice of Sociological Research

Recent debates and controversies have highlighted several issues surrounding sociological research, which relate to the general conditions under which it is undertaken and how this is changing. There is a pressing need to respond to these issues as a whole, in particular by examining what they tell us about research practices. This article argues that a consideration of themes raised by the American television drama The Wire is useful for facilitating such a response, since it may be read as a discussion of working conditions within neoliberal societies. The following themes are pertinent here: the need to reflect upon the terms by which research is framed by funders, to take adequate time to conduct and complete research, and to encourage critical debate within research. Whilst these relate to influential epistemological discussions by Pierre Bourdieu and Michael Burawoy, this reading of The Wire is particularly helpful for highlighting the practical and inter-relational situations in which sociological research is carried out but which tend not to receive the systematic attention they deserve.

Legislating about Unhealthy Food: A Millian Approach

Tackling food-related health conditions is becoming one of the most pressing issues in the policy agendas of western liberal democratic governments. In this article, I intend to illustrate what the liberal philosopher John Stuart Mill would have said about legislation on unhealthy food and I focus especially on the arguments advanced by Mill in his classic essay On Liberty ([1859] 2006). Mill is normally considered as the archetype of liberal anti-paternalism and his ideas are often invoked by those who oppose state paternalism, including those who reject legislation that restricts the consumption of unhealthy food. Furthermore, his views have been applied to related policy areas such as alcohol minimum pricing (Saunders 2013) and genetically modified food (Holtug 2001). My analysis proceeds as follows. First, I show that Mill’s account warrants some restrictions on food advertising and justifies various forms of food labelling. Second, I assess whether and to what extent Mill’s ‘harm principle’ justifies social and legal non-paternalistic penalties against unhealthy eaters who are guilty of other-regarding harm. Finally, I show that Mill’s account warrants taxing unhealthy foods, thus restricting the freedom of both responsible and irresponsible eaters and de facto justifying what I call ‘secondary paternalism’.

Feasibility trial of a film-based educational intervention for increasing boy's and girl's intentions to avoid teenage pregnancy: study protocol

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs. (C) 2014 The Authors. Published by Elsevier Ltd.

Automated versus non-automated weaning for reducing the duration of mechanical ventilation in critically ill adults & children (Review)

Background Automated closed loop systems may improve adaptation of mechanical support for a patient's ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. This review was originally published in 2013 with an update published in 2014. Objectives The primary objective for this review was to compare the total duration of weaning from mechanical ventilation, defined as the time from study randomization to successful extubation (as defined by study authors), for critically ill ventilated patients managed with an automated weaning system versus no automated weaning system (usual care). Secondary objectives for this review were to determine differences in the duration of ventilation, intensive care unit (ICU) and hospital lengths of stay (LOS), mortality, and adverse events related to early or delayed extubation with the use of automated weaning systems compared to weaning in the absence of an automated weaning system. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (OvidSP) (1948 to September 2013); EMBASE (OvidSP) (1980 to September 2013); CINAHL (EBSCOhost) (1982 to September 2013); and the Latin American and Caribbean Health Sciences Literature (LILACS). Relevant published reviews were sought using the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA Database). We also searched the Web of Science Proceedings; conference proceedings; trial registration websites; and reference lists of relevant articles. The original search was run in August 2011, with database auto-alerts up to August 2012. Selection criteria We included randomized controlled trials comparing automated closed loop ventilator applications to non-automated weaning strategies including non-protocolized usual care and protocolized weaning in patients over four weeks of age receiving invasive mechanical ventilation in an ICU. Data collection and analysis Two authors independently extracted study data and assessed risk of bias. We combined data in forest plots using random-effects modelling. Subgroup and sensitivity analyses were conducted according to a priori criteria. Main results We included 21 trials (19 adult, two paediatric) totaling 1676 participants (1628 adults, 48 children) in this updated review. Pooled data from 16 eligible trials reporting weaning duration indicated that automated closed loop systems reduced the geometric mean duration of weaning by 30% (95% confidence interval (CI) 13% to 45%), however heterogeneity was substantial (I2 = 87%, P < 0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not in surgical populations or using other systems. Automated closed loop systems reduced the duration of ventilation (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of an effect on mortality rates, hospital LOS, reintubation rates, self-extubation and use of non-invasive ventilation following extubation. Prolonged mechanical ventilation > 21 days and tracheostomy were reduced in favour of automated systems (relative risk (RR) 0.51, 95% CI 0.27 to 0.95 and RR 0.67, 95% CI 0.50 to 0.90 respectively). Overall the quality of the evidence was high with the majority of trials rated as low risk. Authors' conclusions Automated closed loop systems may result in reduced duration of weaning, ventilation and ICU stay. Reductions are more likely to occur in mixed or medical ICU populations. Due to the lack of, or limited, evidence on automated systems other than Smartcare/PS™ and Adaptive Support Ventilation no conclusions can be drawn regarding their influence on these outcomes. Due to substantial heterogeneity in trials there is a need for an adequately powered, high quality, multi-centre randomized controlled trial in adults that excludes 'simple to wean' patients. There is a pressing need for further technological development and research in the paediatric population.

A simple and low-cost method for the preparation of self-supported TiO2-WO3 ceramic heterojunction wafers

Robust, bilayer heterojunction photodiodes of TiO₂-WO₃ were prepared successfully by a simple, low-cost powder pressing technique followed by heat-treatment. Exclusive photoirradiation of the TiO₂ side of the photodiode resulted in a rapid colour change (dark blue) on the WO₃ surface as a result of reduction of W⁶⁺ to W⁵⁺ (confirmed by X-ray photoelectron spectroscopy). This colour was long lived and shown to be stable in a dry environment in air for several hours. A similar photoirradiation experiment in the presence of a mask showed that charge transfer across the heterojunction occurred approximately normal to the TiO₂ surface, with little smearing out of the mask image. As a result of the highly efficient vectorial charge separation, the photodiodes showed a tremendous increase in photocatalytic activity for the degradation of stearic acid, compared to wafers of the respective individual materials when tested separately.

Developing an international Pseudomonas aeruginosa reference panel

Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis (CF) patients and causes a wide range of infections among other susceptible populations. Its inherent resistance to many antimicrobials also makes it difficult to treat infections with this pathogen. Recent evidence has highlighted the diversity of this species, yet despite this, the majority of studies on virulence and pathogenesis focus on a small number of strains. There is a pressing need for a P. aeruginosa reference panel to harmonize and coordinate the collective efforts of the P. aeruginosa research community. We have collated a panel of 43 P. aeruginosa strains that reflects the organism's diversity. In addition to the commonly studied clones, this panel includes transmissible strains, sequential CF isolates, strains with specific virulence characteristics, and strains that represent serotype, genotype or geographic diversity. This focussed panel of P. aeruginosa isolates will help accelerate and consolidate the discovery of virulence determinants, improve our understanding of the pathogenesis of infections caused by this pathogen, and provide the community with a valuable resource for the testing of novel therapeutic agents.

Sea-level changes in Iceland and the influence of the North Atlantic Oscillation during the last half millennium

We present a new, diatom-based sea-level reconstruction for Iceland spanning the last -500 years, and investigate the possible mechanisms driving the sea-level changes. A sea-level reconstruction from near the Icelandic low pressure system is important as it can improve understanding of ocean-atmosphere forcing on North Atlantic sea-level variability over multi-decadal to centennial timescales. Our reconstruction is from Viarhólmi salt marsh in Snæfellsnes in western Iceland, a site from where we previously obtained a 2000-yr record based upon less precise sea-level indicators (salt-marsh foraminifera). The 20th century part of our record is corroborated by tide-gauge data from Reykjavik. Overall, the new reconstruction shows ca0.6m rise of relative sea level during the last four centuries, of which ca0.2m occurred during the 20th century. Low-amplitude and high-frequency sea-level variability is super-imposed on the pre-industrial long-term rising trend of 0.65m per 1000 years. Most of the relative sea-level rise occurred in three distinct periods: AD 1620-1650, AD 1780-1850 and AD 1950-2000, with maximum rates of ~3±2mm/yr during the latter two of these periods. Maximum rates were achieved at the end of large shifts (from negative to positive) of the winter North Atlantic Oscillation (NAO) Index as reconstructed from proxy data. Instrumental data demonstrate that a strong and sustained positive NAO (a deep Icelandic Low) generates setup on the west coast of Iceland resulting in rising sea levels. There is no strong evidence that the periods of rapid sea-level rise were caused by ocean mass changes, glacial isostatic adjustment or regional steric change. We suggest that wind forcing plays an important role in causing regional-scale coastal sea-level variability in the North Atlantic, not only on (multi-)annual timescales, but also on multi-decadal to centennial timescales.

Human Perception of Laughter from Context-free Whole Body Motion Dynamic Stimuli

Laughter is a ubiquitous social signal in human interactions yet it remains understudied from a scientific point of view. The need to understand laughter and its role in human interactions has become more pressing as the ability to create conversational agents capable of interacting with humans has come closer to a reality. This paper reports on three aspects of the human perception of laughter when context has been removed and only the body information from the laughter episode remains. We report on ability to categorise the laugh type and the sex of the laugher; the relationship between personality factors with laughter categorisation and perception; and finally the importance of intensity in the perception and categorisation of laughter.

Finding Merit in Judicial Appointments: NIJAC and the Search for a New Judiciary in Northern Ireland

The post-Agreement constitutional architecture has produced a new legal space in Northern Ireland. While the court structure has largely endured in a recognisable format there are perhaps now new expectations of how it will function in the next stage of Northern Ireland’s transition from a society in conflict. These expectations come into focus around the nature and role of the judiciary that is to oversee this new legal space. At the same time there are other, wider forces pressing upon the judiciary across the United Kingdom and these are being acted out in the various appointment commissions and regimes that have been created to modernise the judiciary. This all contributes to establishing a dynamic context for considering whether and/or how the judiciary in Northern Ireland is changing, and the forces that may be conditioning any change. This chapter looks at some of the expectations that might arise for the judiciary. It focuses both on some ideas about what might be the role of a judge in a transitional context, and the debate about how judges generally should be appointed across the United Kingdom where the idea of “merit” emerges as governing concept. Next consideration is given to how this idea of merit plays out in the Northern Ireland context and, in particular, how it impacts on the appointment of women to senior judicial roles which has emerged as the central concern in the new dispensation. Here the chapter draws on two pieces of research: the first looking at the issues surrounding judicial appointments and attitudes towards seeking such posts in the Northern Ireland context, and a second project where the idea of “merit” as a governing factor in judicial appointment was further explored in focus groups and interviews. Finally the chapter looks ahead at the challenges around judicial appointment that remain and suggests that notion of ‘merit’ has not provided the robust foundation which its proponents imagined it would.

A multi-proxy chronological reconstruction of palaeosalinity in the eastern Limfjord, Denmark

The Jutland peninsula in northern Denmark is home to the Limfjord, one of the largest estuarine bodies of water in the region. Human inhabitance of the Limfjord’s surrounding coastlines stretches back further than 7,800 cal BP, with anthropogenic influence on the landscape beginning approximately 6,000 cal BP. Understanding how the Limfjord as a system has changed throughout time is useful in comprehending subsistence patterns and anthropogenic influence. This research is part of a larger project aimed at discerning subsistence patterns and environmental change in the region. Following the Younger Dryas, as the Fennoscandian ice sheet began to melt, Denmark experienced isostatic rebound, which contributed to the complex sea level history in the region. Between ice melt and isostatic rebound, the Jutland peninsula experienced many transgression and regression events. Connections to surrounding seas have shifted throughout time, with most attention focused on the western connection of the Limfjord with the North Sea, which has experienced numerous closures and subsequent re-openings throughout the Holocene. Furthermore, the Limfjord-North Sea connection has been the focal point of research because of the west to east water flow in the system, and the present day higher salinity in the west compared to the east. Little to no consideration has been paid to the influence of the Kattegat and Baltic on the Limfjord until now. A 10m sediment core was taken from Sebbersund (near Nibe, Limfjord), along the connection between the Limfjord and the Kattegat in the east to understand how the eastern part of the system has changed and differed from changes observed in the west. The Sebbersund sequence spans a majority of the Holocene, from 9600 cal BP to 1030 cal BP, determined via radiocarbon dating of terrestrial macrofossils and bulk sediment. Over this time period palaeoenvironmental conditions were reconstructed through the use of geochemical analyses (13C, 15N, C:N), physical sediment analyses, dinoflagellate cyst abundances and molluscan analyses. apart from two instances of low salinity, one at the top and one at the bottom of the core, the sequence has a strong marine signal for a majority of the Holocene. Radiocarbon dating of bulk sediment samples showed the presence of old carbon in the system, creating an age offset between 1,300 ± 200 and 2,800 ± 200 calibrated 14C years compared to the age-depth curve based on the terrestrial macrofossils. This finding, along with the strong marine influence in the system, discerned through geochemical data, dinoflagellate cyst and mollusc counts, is important for obtaining accurate radiocarbon ages in the region and stresses the importance of understanding both the marine and freshwater reservoir effects. The marine dominance in the eastern Limfjord differs from the west, which is characterized by a number of freshwater events when the North Sea connection was closed off during the Holocene. The eastern connection was open to the Kattegat throughout a large portion of the Holocene, with influx of open ocean water entering the system during periods of higher sea level.

The progress in understanding and treatment of diabetic retinopathy

In most countries, diabetic retinopathy is the most frequently occurring complication of diabetes mellitus and remains a leading cause of vision loss globally. Its etiology and pathology have been extensively studied for half a century, yet there are disappointingly few therapeutic options. Although some new treatments have been introduced for diabetic macular edema (DME) (e.g. intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') and new steroids), up to 50% of patients fail to respond. Furthermore, for people with proliferative diabetic retinopathy (PDR), laser photocoagulation remains a mainstay therapy, even though it is inherently a destructive procedure. This review summarizes the clinical features of diabetic retinopathy and its risk factors. It describes details of retinal pathology and the cell culture approaches and animal models that are used to mimic its key components, advance understanding of its pathogenesis, and enable identification of new therapeutic targets. We emphasise that although there have been significant advances, there is still a pressing need for a better understanding basic mechanisms to enable development of reliable and robust means to identify patients at highest risk, and to intervene effectively before vision loss occurs.

Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment

BACKGROUND: Pancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU) is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU.

RESULTS: 5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than β-catenin.

CONCLUSION: Our findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells.

Biocontrol agents promote growth of potato pathogens, depending on environmental conditions

There is a pressing need to understand and optimize biological control so as to avoid over-reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol-strain, Bacillus sp. JC12GB43, and potato-pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near-complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out-perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth-rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2-M glycerol) by up to 570%. Culture-based assays involving macromolecule-stabilizing (kosmotropic) compatible solutes provided proof-of-principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field-relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode-of-behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain.

Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.