Mechanisms to improve integrative research at the science-policy interface for sustainable catchment management

Greater integration between researchers and policy makers is required to provide an evidence base that is transparent, integrated, and adaptive to support the complexities of sustainable catchment management. Opening-up and closing-down mechanisms are equally important in creating and establishing such an evidence base. We provide examples of both types based on our recent research and knowledge-transfer activities at the science-policy interface. Through our coordination role for the United Kingdom government we provide opening up physical and virtual forums for researchers and government science and policy staff to learn about and assess the gaps and uncertainties of the evidence base. Closing-down mechanisms are vital to policy cycles, in that they distil what is known and what is unknown. The Diffuse Pollution User Manual provides a valuable tool for policy and catchment management staff to assess the potential effectiveness of different combinations of remedial diffuse-pollution mitigation methods. It is vital that that opening-up and closing-down mechanisms are iteratively linked given the complexity and uncertainty of the science and policy cycles. Advances in integrative research at the science-policy interface are vital if there is to be a move to more deliberative policy making

SYSTEMS-2: a randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM). Standard palliative (20Gy/5#) or dose escalated treatment (36Gy/6#) will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM

Cost-benefit analysis for commissioning decisions in GEO600

Gravitational wave interferometers are complex instruments, requiring years of commissioning to achieve the required sensitivities for the detection of gravitational waves, of order 10^-21 in dimensionless detector strain, in the tens of Hz to several kHz frequency band. Investigations carried out by the GEO600 detector characterisation group have shown that detector characterisation techniques are useful when planning for commissioning work. At the time of writing, GEO600 is the only large scale laser interferometer currently in operation running with a high duty factor, 70%, limited chiefly by the time spent commissioning the detector. The number of observable gravitational wave sources scales as the product of the volume of space to which the detector is sensitive and the observation time, so the goal of commissioning is to improve the detector sensitivity with the least possible detector down time. We demonstrate a method for increasing the number of sources observable by such a detector, by assessing the severity of non-astrophysical noise contaminations to efficiently guide commissioning. This method will be particularly useful in the early stages and during the initial science runs of the aLIGO and adVirgo detectors, as they are brought up to design performance.Comment: 17 pages, 17 figures, 2 table

Methanol Masers as Tracers of Circumstellar Disks

We show that in many methanol maser sources the masers are located in lines, with a velocity gradient along them which suggests that the masers are situated in edge-on circumstellar, or protoplanetary, disks. We present VLBI observations of the methanol maser source G309.92+0.48, in the 12.2 GHz transition, which confirm previous observations that the masers in this source lie along a line. We show that such sources are not only linear in space but, in many cases, also have a linear velocity gradient. We then model these and other data in both the 6.7 GHz and the 12.2 GHz transition from a number of star formation regions, and show that the observed spatial and velocity distribution of methanol masers, and the derived Keplerian masses, are consistent with a circumstellar disk rotating around an OB star. We consider this and other hypotheses, and conclude that about half of these methanol masers are probably located in edge-on circumstellar disks around young stars. This is of particular significance for studies of circumstellar disks because of the detailed velocity information available from the masers.Comment: 38 pages, 13 figures accepted by Ap

Are better communicators better readers? : an exploration of the connections between narrative language and reading comprehension

The association between receptive language skills and reading comprehension has been established in the research literature. Even when the importance of receptive skills for reading comprehension has been strongly supported, in practice lower levels of skills tend to go unnoticed in typically developing children. A potentially more visible modality of language, expressive skills using speech samples, has been rarely examined despite the longitudinal links between speech and later reading development, and the connections between language and reading impairments. Even fewer reading studies have examined expressive skills using a subgroup of speech samples – narrative samples – which are closer to the kind of language practitioners can observe in their classrooms, and are also a rich source of linguistic and discourse-level data in school-aged children. This thesis presents a study examining the relationship between expressive language skills in narrative samples and reading comprehension after the first two years of formal reading instruction, with considerable attention given to methodological and developmental issues. In order to address the main methodological issues surrounding the identification of the optimal linguistic indices in terms of reliability and the existence of developmental patterns, two studies of language development in oral narratives were carried out. The first of the narrative language studies drew data from an existing corpus, while the other analysed primary data, collected specifically for this purpose. Having identified the optimal narrative indices in two different samples, the main study examined the relationships between these expressive narrative measures along with receptive standardised measures, and reading comprehension in a monolingual sample of eighty 7- and 8-year-old children attending Year 3 in the UK. Both receptive and expressive oral language skills were assessed at three different levels: vocabulary, grammar and discourse. Regression analyses indicated that, when considering expressive narrative variables on their own, expressive grammar and vocabulary, in that order, contributed to explain over a fifth of reading comprehension variance in typically developing children. When controlling for receptive language however, expressive skills were not able to account for significant unique variance in the outcome measure. Nonetheless, mediation analyses revealed that receptive vocabulary and grammar played a mediating role in the relationship between expressive skills from narratives and reading comprehension. Results and further research directions are discussed in the context of this study’s methodological considerations.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

GEO 600 and the GEO-HF upgrade program: successes and challenges

The German-British laser-interferometric gravitational wave detector GEO 600 is in its 14th year of operation since its first lock in 2001. After GEO 600 participated in science runs with other first-generation detectors, a program known as GEO-HF began in 2009. The goal was to improve the detector sensitivity at high frequencies, around 1 kHz and above, with technologically advanced yet minimally invasive upgrades. Simultaneously, the detector would record science quality data in between commissioning activities. As of early 2014, all of the planned upgrades have been carried out and sensitivity improvements of up to a factor of four at the high-frequency end of the observation band have been achieved. Besides science data collection, an experimental program is ongoing with the goal to further improve the sensitivity and evaluate future detector technologies. We summarize the results of the GEO-HF program to date and discuss its successes and challenges

Regulating Access to Adult Content (with Privacy Preservation)

In the physical world we have well-established mechanisms for keeping children out of adult-only areas. In the virtual world this is generally replaced by self declaration. Some service providers resort to using heavy-weight identification mechanisms, judging adulthood as a side effect thereof. Collection of identification data arguably constitutes an unwarranted privacy invasion in this context, if carried out merely to perform adulthood estimation. This paper presents a mechanism that exploits the adult's more extensive exposure to public media, relying on the likelihood that they will be able to recall details if cued by a carefully chosen picture. We conducted an online study to gauge the viability of this scheme. With our prototype we were able to predict that the user was a child 99% of the time. Unfortunately the scheme also misclassified too many adults. We discuss our results and suggest directions for future research

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

OCT2013, an ischaemia-activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine

Background and Purpose Sudden cardiac death (SCD) caused by acute myocardial ischaemia and ventricular fibrillation (VF) is an unmet therapeutic need. Lidocaine suppresses ischaemia-induced VF, but its utility is limited by side effects and a narrow therapeutic index. Here, we characterise OCT2013, a putative ischaemia-activated prodrug of lidocaine. Experimental Approach The rat Langendorff-perfused isolated heart, anaesthetised rat and rat ventricular myocyte preparations were utilised in a series of blinded and randomised studies to investigate the antiarrhythmic effectiveness, adverse effects and mechanism of action of OCT2013, compared with lidocaine. Key Results In isolated hearts, OCT2013 and lidocaine prevented ischaemia-induced VF equi-effectively, but OCT2013 did not share lidocaine's adverse effects (PR widening, bradycardia and negative inotropy). In anaesthetised rats, i.v. OCT2013 and lidocaine suppressed VF and increased survival equi-effectively; OCT2013 had no effect on cardiac output even at 64 mg·kg⁻¹ i.v., whereas lidocaine reduced it even at 1 mg·kg⁻¹. In adult rat ventricular myocytes, OCT2013 had no effect on Ca²⁺ handling, whereas lidocaine impaired it. In paced isolated hearts, lidocaine caused rate-dependent conduction slowing and block, whereas OCT2013 was inactive. However, during regional ischaemia, OCT2013 and lidocaine equi-effectively hastened conduction block. Chromatography and MS analysis revealed that OCT2013, detectable in normoxic OCT2013-perfused hearts, became undetectable during global ischaemia, with lidocaine becoming detectable. Conclusions and Implications OCT2013 is inactive but is bio-reduced locally in ischaemic myocardium to lidocaine, acting as an ischaemia-activated and ischaemia-selective antiarrhythmic prodrug with a large therapeutic index, mimicking lidocaine's benefit without adversity