Exploring the relative efficacy of motion artefact correction techniques for EEG data acquired during simultaneous fMRI

Simultaneous EEG-fMRI allows multi-parametric characterisation of brain function, in principle enabling a more complete understanding of brain responses; unfortunately the hostile MRI environment severely reduces EEG data quality. Simply eliminating data segments containing gross motion artefacts [MAs] (generated by movement of the EEG system and head in the MRI scanner’s static magnetic field) was previously believed sufficient. However recently the importance of removal of all MAs has been highlighted and new methods developed.A systematic comparison of the ability to remove MAs and retain underlying neuronal activity using different methods of MA detection and post-processing algorithms is needed to guide the neuroscience community. Using a head phantom, we recorded MAs while simultaneously monitoring the motion using three different approaches: Reference Layer Artefact Subtraction (RLAS), Moire Phase Tracker (MPT) markers, and Wire Loop Motion Sensors (WLMS). These EEG recordings were combined with EEG responses to simple visual tasks acquired on a subject outside the MRI environment. MAs were then corrected using the motion information collected with each of the methods combined with different analysis pipelines.All tested methods retained the neuronal signal. However, often the MA was not removed sufficiently to allow accurate detection of the underlying neuronal signal. We show that the MA is best corrected using the RLAS combined with post-processing using a multi-channel, recursive least squares (M-RLS) algorithm. This method needs to be developed further to enable practical utility; thus, WLMS combined with M-RLS currently provides the best compromise between EEG data quality and practicalities of motion detection

Spermatogenesis and sertoli cell activity in mice lacking Sertoli cell receptors for follicle stimulating hormone and androgen

Spermatogenesis in the adult male depends on the action of FSH and androgen. Ablation of either hormone has deleterious effects on Sertoli cell function and the progression of germ cells through spermatogenesis. In this study we generated mice lacking both FSH receptors (FSHRKO) and androgen receptors on the Sertoli cell (SCARKO) to examine how FSH and androgen combine to regulate Sertoli cell function and spermatogenesis. Sertoli cell number in FSHRKO-SCARKO mice was reduced by about 50% but was not significantly different from FSHRKO mice. In contrast, total germ cell number in FSHRKO-SCARKO mice was reduced to 2% of control mice (and 20% of SCARKO mice) due to a failure to progress beyond early meiosis. Measurement of Sertoli cell-specific transcript levels showed that about a third were independent of hormonal action on the Sertoli cell, whereas others were predominantly androgen dependent or showed redundant control by FSH and androgen. Results show that FSH and androgen act through redundant, additive, and synergistic regulation of spermatogenesis and Sertoli cell activity. In addition, the Sertoli cell retains a significant capacity for activity, which is independent of direct hormonal regulation

Modeling the variability of shapes of a human placenta

While it is well-understood what a normal human placenta should look like, a deviation from the norm can take many possible shapes. In this paper we propose a mechanism for this variability based on the change in the structure of the vascular tree

Update on Standard Operating Procedures in Preclinical Research for DMD and SMA Report of TREAT-NMD Alliance Workshop, Schiphol Airport, 26 April 2015, The Netherlands

A workshop took place in 2015 to follow up TREAT-NMD activities dedicated to improving quality in the preclinical phase of drug development for neuromuscular diseases. In particular, this workshop adressed necessary future steps regarding common standard experimental protocols and the issue of improving the translatability of preclinical efficacy studies

Ruminant neurological disease: a retrospective cohort study

Between January 2006 and June 2016, 96 ruminants with neurological signs were donated to the Scottish Centre for Production Animal Health and Food Safety (SCPAHFS), University of Glasgow, by veterinarians in the field representing 5.4 per cent of all submissions. Forty-seven different neurological presenting signs were reported with 79 per cent of the donated patients presenting with abnormal gait. All cases presenting with abnormalities in more than 4 out of 10 neurological categories died or were euthanased on welfare grounds. Calves were significantly more likely to present with neurological disorders than adult cattle compared with the proportion of calves: cows in the Scottish cattle population and total case population donated to SCPAHFS. Lesions were most commonly localised to the spinal cord in sheep 47 per cent (16), the peripheral nervous system in cattle 45 per cent (28) and to the brain in the overall population 41 per cent (39). The most common aetiology of neurological pathologies observed was infectious or inflammatory 28 per cent (27). Definitive diagnoses could be reached in 84 per cent (81) of patients. When postmortem reports were available, they produced a diagnosis in 70 per cent (52) of cases and contradicted clinical diagnoses in 38 per cent (26) of cases. The most frequently diagnosed conditions in ruminants over the 10 years were spastic paresis, vertebral osteomyelitis and listeriosis

Global signal modulation of single-trial fMRI response variability: effect on positive vs negative BOLD response relationship

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses

Water security in times of climate change and intractability : Reconciling conflict by transforming security concerns into equity concerns

This paper considers how to achieve equitable water governance and the flow-on effects it has in terms of supporting sustainable development, drawing on case studies from the international climate change adaptation and governance project (CADWAGO). Water governance, like many other global issues, is becoming increasingly intractable (wicked) with climate change and is, by the international community, being linked to instances of threats to human security, thewar in the Sudanese Darfur and more recently the acts of terrorism perpetuated by ISIS. In this paper, we ask the question: how can situations characterized by water controversy (exacerbated by the uncertainties posed by climate change) be reconciled? The main argument is based on a critique of the way the water security discourse appropriates expert (normal) claims about human-biophysical relationships. When water challenges become increasingly securitized by the climate change discourse it becomes permissible to enact processes that legitimately transgress normative positions through post-normal actions. In contrast, the water equity discourse offers an alternative reading of wicked and post-normal water governance situations. We contend that by infusing norm critical considerations into the process of securitization, new sub-national constellations of agents will be empowered to enact changes; thereby bypassing vicious cycles of power brokering that characterize contemporary processes intended to address controversies

Using Administrative Data to Count Local Populations

There is growing evidence that official population statistics based on the decennial census are inaccurate at the local authority level—the fundamental administrative unit of the UK. This paper investigates the use of locally available administrative data sets for counting populations. The method uses truth tables for combining different data sources with different population coverage according to a defined and therefore replicable set of rules. The result is timelier and geographically more flexible data which is more cost-effective to produce than a survey-based census. Associated techniques for linking diverse data sources at individual and household level are briefly discussed. The methodology is then applied to administrative data from a London borough with about 170,000 people. The results are evaluated and compared with other population sources. The paper concludes by discussing potential improvements including scaling up the work to cover multiple local authorities. The practicalities of using alternative central government data sets are briefly considered. A sequel paper in this journal provides examples of key applications of this approach at local level

Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy