Responsible research and innovation: A manifesto for empirical ethics?

In 2013 the Nuffield Council on Bioethics launched their report Novel Neurotechnologies: Intervening in the Brain. The report, which adopts the European Commission's notion of Responsible Research and Innovation, puts forward a set of priorities to guide ethical research into, and the development of, new therapeutic neurotechnologies. In this paper, we critically engage with these priorities. We argue that the Nuffield Council's priorities, and the Responsible Research and Innovation initiative as a whole, are laudable and should guide research and innovation in all areas of healthcare. However, we argue that operationalising Responsible Research and Innovation requires an in-depth understanding of the research and clinical contexts. Providing such an understanding is an important task for empirical ethics. Drawing on examples from sociology, science and technology studies, and related disciplines, we propose four avenues of social science research which can provide such an understanding. We suggest that these avenues can provide a manifesto for empirical ethics.The paper derives from a project that was funded by Wellcome Trust (Wellcome Trust Biomedical Strategic Award 086034)

Fronto-striatal cognitive deficits at different stages of Parkinson's disease

Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the 'Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and 'early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease

Cognitive performance in multiple system atrophy

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered

A Comprehensive Radio and Optical Study of Abell 2256: Activity from an Infalling Group

Abell 2256 is a nearby (z~0.06), rich cluster of galaxies with fascinating observed properties across a range of wavelengths. Long believed to represent a cluster merger, recent X-ray and optical results have suggested that in addition to the primary cluster and subcluster there is evidence for a third, poorer system. We present wide-field, high sensitivity 1.4 GHz VLA radio observations of Abell 2256 in conjunction with optical imaging and additional spectroscopy. Over 40 cluster radio galaxies are identified, with optical spectroscopy indicating the emission source (star formation or AGN) for most of them. While the overall fraction of galaxies exhibiting radio emission is consistent with a large sample of other nearby clusters, we find an increase in the activity level of galaxies belonging to the third system (hereafter, the ``Group''). Specifically, the Group has relatively more star formation than both the primary cluster and main subcluster. The position of the Group is also coincident with the observed cluster radio relic. We suggest that the Group recently (~0.3 Gyr) merged with the primary cluster and that this merger, not the ongoing merger of the primary and the main subcluster, might be responsible for many of the unusual radio properties of Abell 2256. Furthermore, the greater star formation activity of the Group suggests that the infall of groups is an important driver of galaxy evolution in clusters.Comment: 21 pages plus 13 JPEG figures; to appear in the Astronomical Journa

Technical Note: Field experiences using UV/VIS sensors for high-resolution monitoring of nitrate in groundwater

peer-reviewedTwo different in situ spectrophotometers are compared that were used in the field to determine nitrate-nitrogen (NO3-N) concentrations at two distinct spring discharge sites. One sensor was a double wavelength spectrophotometer (DWS) and the other a multiple wavelength spectrophotometer (MWS). The objective of the study was to review the hardware options, determine ease of calibration, accuracy, influence of additional substances and to assess positive and negative aspects of the two sensors as well as troubleshooting and trade-offs. Both sensors are sufficient to monitor highly time-resolved NO3-N concentrations in emergent groundwater. However, the chosen path length of the sensors had a significant influence on the sensitivity and the range of detectable NO3-N. The accuracy of the calculated NO3-N concentrations of the sensors can be affected if the content of additional substances such as turbidity, organic matter, nitrite or hydrogen carbonate significantly varies after the sensors have been calibrated to a particular water matrix. The MWS offers more possibilities for calibration and error detection but requires more expertise compared with the DWS.The authors would like to acknowledge the Teagasc Walsh Fellowship scheme for funding the study in Ireland, and the German federal Ministry of Education and Research (BMBF) for sponsoring the SMART-project (grant no. 02WM1079-1086, 02WM1211-1212) for the study in Jordan.Teagasc Walsh Fellowship Programm

Mobilisation or dilution? Nitrate response of karst springs to high rainfall events

peer-reviewedNitrate (NO3−) contamination of groundwater associated with agronomic activity is of major concern in many countries. Where agriculture, thin free draining soils and karst aquifers coincide, groundwater is highly vulnerable to nitrate contamination. As residence times and denitrification potential in such systems are typically low, nitrate can discharge to surface waters unabated. However, such systems also react quickest to agricultural management changes that aim to improve water quality. In response to storm events, nitrate concentrations can alter significantly, i.e. rapidly decreasing or increasing concentrations. The current study examines the response of a specific karst spring situated on a grassland farm in South Ireland to rainfall events utilising high-resolution nitrate and discharge data together with on-farm borehole groundwater fluctuation data. Specifically, the objectives of the study are to formulate a scientific hypothesis of possible scenarios relating to nitrate responses during storm events, and to verify this hypothesis using additional case studies from the literature. This elucidates the controlling key factors that lead to mobilisation and/or dilution of nitrate concentrations during storm events. These were land use, hydrological condition and karstification, which in combination can lead to differential responses of mobilised and/or diluted nitrate concentrations. Furthermore, the results indicate that nitrate response in karst is strongly dependent on nutrient source, whether mobilisation and/or dilution occur and on the pathway taken. This will have consequences for the delivery of nitrate to a surface water receptor. The current study improves our understanding of nitrate responses in karst systems and therefore can guide environmental modellers, policy makers and drinking water managers with respect to the regulations of the European Union (EU) Water Framework Directive (WFD). In future, more research should focus on the high-resolution monitoring of karst aquifers to capture the high variability of hydrochemical processes, which occur at time intervals of hours to days.Teagasc Walsh Fellowship Programm

Isolation of Unknown Genes from Human Bone Marrow by Differental Screening and Single-Pass cDNA Sequences Determination

A cDNA sequencing project was initiated to characterize gene expression in human bone marrow and develop strategies to isolate novel genes. Forty-eight random cDNAs from total human bone marrow were subjected to single-pass DNA sequence analysis to determine a limited complexity of mRNAs expressed in the bone marrow. Overall, 8 cDNAs (17%) showed no similarity to known sequences. Information from DNA sequence analysis was used to develop a differential prescreen to subtract unwanted cDNAs and to enrich for unknown cDNAs. Forty-eight cDNAs that were negative with a complex probe were subject to single-pass DNA sequence determination. Of these prescreened cDNAs, the number of unknown sequences increased to 23 (48%). Unknown cDNAs were also characterized by RNA expression analysis using 25 different human leukemic cell lines. Of 13 unknown cDNAs tested, 10 were expressed in all cell types tested and 3 revealed a hematopoietic lineage-restricted expression pattern. Interestingly, while a total of only 96 bone marrow cDNAs were sequenced, 31 of these cDNAs represent sequences from unknown genes and 12 showed significant similarities to sequences in the data bases. One cDNA revealed a significant similarity to a serine/threonine-protein kinase at the amino acid level (56% identity for 123 amino acids) and may represent a previously unknown kinase. Differential screening techniques coupled with single-pass cDNA sequence analysis may prove to be a powerful and simple technique to examine developmental gene expression

The Complex Core of Abell 2199: The X-ray and Radio Interaction

The cluster Abell 2199 is one of the prototypical ``cooling flow'' clusters. Its central cD galaxy is host to a steep-spectrum radio source, of the type associated with cooling cores. In this paper we combine radio data with new ROSAT HRI data to show that conditions in its inner core, less than 50 kpc, are complex and interesting. Energy and momentum flux from the radio jet have been significant in the dynamics of the gas in the core. In addition, the Faraday data detects a dynamically important magnetic field there. The core of the X-ray luminous gas is not a simple, spherically symmetric cooling inflow. In addition, we believe the X-ray gas has had strong effects on the radio source. It seems to have disrupted the jet flow, which has led to dynamical history very different from the usual radio galaxy. This particular source is much younger than the galaxy, which suggests the disruptive effects lead to an on-off duty cycle for such sources.Comment: 16 pages, 8 figures, Latex, to appear in the Astrophysical Journna

Animal movement modelling: Independent or dependent models?

Hidden Markov models have become a popular time series method for the analysis of GPS tracked animals. Their advantage for identifying latent behavioural states compared with Independent Mixture models is that they take into account the time series dependency of successive displacement distances by the tracked animals. However, little is known about how the analysis results may differ depending on which of these approaches is used. We compared the results and interpretations obtained from fitting Hidden Markov and Independent Mixture models to simulated movement data as well as to field data recording the hourly movements of sable antelope and buffalo within the Kruger National Park, South Africa. Hidden Markov models consistently yielded narrower confidence intervals around parameters and smaller standard errors than simpler time independent mixture models, but for some data the improvement was marginal and the Independent Mixture model provided an adequate alternative for identifying the latent behavioural states of the animal. In general, it is expected Hidden Markov models will provide the better balance between model complexity and extensibility for animal movement modelling from a statistical perspective. However, in some cases, Independent Mixture models could provide an adequate alternative method and might be more faithful biologically