Magnetic variation anomalies in northern England and southern Scotland

Single-station transfer functions linking the time variations of the vertical and horizontal components of the magnetic field at stations in northern England and southern Scotland have been compiled into a uniform data set. From hypothetical event analysis we show here that there are two distinct anomalies in the Borders region. One runs south-west to north-east, immediately to the south-east of the Southern Uplands Fault; the second follows the Northumberland Basin, and seems to exist because the conductive sedimentary rocks filling the basin create a link between the Irish and North Seas. If the Iapetus suture is marked by a conductivity anomaly, as has been suggested, these results place it beneath the Southern Uplands, unless it is masked by the surface conductor in the Northumberland Basin

Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects

Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics; however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered

Sustainable deltas in a changing world

Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise due to multiple climatic, environmental and socio-economic drivers, with the potential for mass environmental change and displacement of exposed populations. Populations in deltas are however already highly mobile, with significant urbanization trends driven primarily by economic opportunity. Yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on understanding what sustainability means within such a dynamic context and how this informs regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to assess sustainability in delta regions. It is based on a new integrated methodology to assess deltas, and most particularly migration in those deltas. It uses the Volta delta (Ghana), Mahanadi delta (India) and Ganges-Brahmaputra-Meghna delta (India and Bangladesh) as case studies. Our integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and/or enable adaptation. Initial results suggest that migration decision-making strongly interacts with diverse measures for adaptation of land, water and agricultural management. Any notion of sustainability in such dynamic environments cannot be static and must consider and steer these large-scale trends towards more desirable goals

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

Structure-Based Design of Potent and Selective Leishmania N-Myristoyltransferase Inhibitors

Inhibitors of Leishmania N-myristoyltransferase (NMT), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. Crystal structures bound to Leishmania major NMT were obtained, and the active diastereoisomer of one of the inhibitors was identified. On the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent Leishmania donovani NMT inhibitors with good selectivity over the human enzyme

Inflammatory complications of CGRP monoclonal antibodies: a case series

BACKGROUND: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. CASES: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. CONCLUSION: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward

Choices: Future Trade-Offs and Plausible Pathways

Policy development and management of deltas in the Anthropocene involves the consideration of trade-offs and the balancing of positive and negative consequences for delta functions and the societies that rely on them. This assessment outlines policy-driven and spatial trade-offs that dominate the landscape of choice. It highlights examples of such trade-offs using plausible delta futures and the governance choices associated with them. The analysis is based on modelling broad-scale processes and individual adaptive actions. It highlights how policy choices to maximise economic growth can, for example, have unforeseen consequences such as diminished well-being for some populations. Hence the chapter concludes that trade-offs are a crucial governance challenge for future sustainability of deltas