Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques

BACKGROUND: Short-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear. OBJECTIVE: To compare T-SICI and its reliability with conventional A-SICI measurements. METHODS: In twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50-80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator. RESULTS: Across the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7-0.3x, R2 = 0.99), but there was considerable interindividual variability. At CS 60-80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81-0.92) and adequate-to-excellent interday (ICC 0.61-0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17-0.42 intraday, 0.37-0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies. CONCLUSION: The close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique

Conventional and threshold-tracking transcranial magnetic stimulation tests for single-handed operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short-and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short-and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single-and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single-and paired-pulse TMS protocols. This paper shows how to record a number of single-and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS

Short interval intracortical inhibition: Variability of amplitude and threshold-tracking measurements with 6 or 10 stimuli per point

Reduced short-interval intracortical inhibition (SICI) in motor neuron disease has been demonstrated by amplitude changes (A-SICI) and threshold-tracking (T-SICI) using 10 stimuli per inter-stimulus interval (ISI). To test whether fewer stimuli would suffice, A-SICI and T-SICI were recorded twice from 30 healthy subjects using 6 and 10 stimuli per ISI. Using fewer stimuli increased mean A-SICI variances by 23.8% but the 7.3% increase in T-SICI variance was not significant. We conclude that our new parallel threshold-tracking SICI protocol, with 6 stimuli per ISI, can reduce time and stimulus numbers by 40% without appreciable loss of accuracy

The Gregory-Laflamme instability for the D2-D0 bound state

The D2-D0 bound state exhibits a Gregory-Laflamme instability when it is sufficiently non-extremal. If there are no D0-branes, the requisite non-extremality is finite. When most of the extremal mass comes from D0-branes, the requisite non-extremality is very small. The location of the threshhold for the instability is determined using a local thermodynamic analysis which is then checked against a numerical analysis of the linearized equations of motion. The thermodynamic analysis reveals an instability of non-commutative field theory at finite temperature, which may occur only at very long wavelengths as the decoupling limit is approached.Comment: 19 pages, Latex2e. v2: two refs added. v3: clearer exposition in section

The flux and provenance of dust delivered to the SW Pacific during the last glacial maximum

The funding for the TAN1106 voyage was from the Coasts and Oceans Physical Resources program awarded to the National Institute of Water and Atmospheric Research, New Zealand. This work was funded by NERC studentship NE/L002531/1 to R.S. and NERC grant NE/J021075/1 to G.L.F. R.G. and A.B. were supported by NERC grant NE/M004619/1 awarded to A.B.Atmospheric dust is a primary source of iron (Fe) to the open ocean, and its flux is particularly important in the high nutrient, low chlorophyll (HNLC) Southern Ocean where Fe currently limits productivity. Alleviation of this Fe limitation in the Subantarctic Zone of the Atlantic by increased dust-borne Fe supply during glacial periods has been shown to increase primary productivity. However, previous work has found no such increase in productivity in the Pacific sector. In order to constrain the relative importance of Southern Ocean Fe fertilization on glacial-interglacial carbon cycles, records of dust fluxes outside of the Atlantic sector of the Southern Ocean at the Last Glacial Maximum (LGM) are required. Here we use grain size and U-series analyses to reconstruct lithogenic and CaCO3 fluxes, and Nd, Sr and Pb isotopes to ascertain the provenance of terrigenous material delivered to four deep-water cores in the SW Pacific Ocean over the last ~30kyr. We find evidence for an increase in the relative proportion of fine-grained (0.5-12 ?m) terrigenous sediment and higher detrital fluxes during the LGM compared to the Holocene. The provenance of the LGM dust varied spatially, with an older, more "continental" signature (low εNd, high 87Sr/86Sr) sourced from Australia in the northern cores, and a younger, more volcanogenic source in the southern cores (high εNd, low 87Sr/86Sr), likely sourced locally from New Zealand. Given this increase in lithogenic flux to the HNLC subantarctic Pacific Southern Ocean during the LGM, factors besides Fe-supply must have regulated the biological productivity here.Publisher PDFPeer reviewe

Conceptually driven and visually rich tasks in texts and teaching practice: the case of infinite series

The study we report here examines parts of what Chevallard calls the institutional dimension of the students’ learning experience of a relatively under-researched, yet crucial, concept in Analysis, the concept of infinite series. In particular, we examine how the concept is introduced to students in texts and in teaching practice. To this purpose, we employ Duval's Theory of Registers of Semiotic Representation towards the analysis of 22 texts used in Canada and UK post-compulsory courses. We also draw on interviews with in-service teachers and university lecturers in order to discuss briefly teaching practice and some of their teaching suggestions. Our analysis of the texts highlights that the presentation of the concept is largely a-historical, with few graphical representations, few opportunities to work across different registers (algebraic, graphical, verbal), few applications or intra-mathematical references to the concept's significance and few conceptually driven tasks that go beyond practising with the application of convergence tests and prepare students for the complex topics in which the concept of series is implicated. Our preliminary analysis of the teacher interviews suggests that pedagogical practice often reflects the tendencies in the texts. Furthermore, the interviews with the university lecturers point at the pedagogical potential of: illustrative examples and evocative visual representations in teaching; and, student engagement with systematic guesswork and writing explanatory accounts of their choices and applications of convergence tests

Comparison of figure-of-8 and circular coils for threshold tracking transcranial magnetic stimulation measurements

OBJECTIVES: The transcranial magnetic stimulation (TMS) technique of threshold-tracking short-interval intracortical inhibition (T-SICI) has been proposed as a diagnostic tool for amyotrophic lateral sclerosis (ALS). Most of these studies have used a circular coil, whereas a figure-of-8 coil is usually recommended for paired-pulse TMS measurements. The aim of this study was to compare figure-of-8 and circular coils for T-SICI in the upper limb, with special attention to reproducibility, and the pain or discomfort experienced by the subjects. METHODS: Twenty healthy subjects (aged: 45.5 ± 6.7, mean ± SD, 9 females, 11 males) underwent two examinations with each coil, in morning and afternoon sessions on the same day, with T-SICI measured at interstimulus intervals (ISIs) from 1-7 ms. After each examination the subjects rated degree of pain/discomfort from 0 to 10 using a numerical rating scale (NRS). RESULTS: Mean T-SICI was higher for the figure-of-8 than for the circular coil at ISI of 2 ms (p < 0.05) but did not differ at other ISIs. Intra-subject variability did not differ between coils, but mean inhibition from 1-3.5 ms was less variable between subjects with the figure-of-8 coil (SD 7.2% vs. 11.2% RMT, p < 0.05), and no such recordings were without inhibition (vs. 6 with the circular coil). The subjects experienced less pain/discomfort with the figure-of-8 coil (mean NRS: 1.9 ± 1.28 vs 2.8 ± 1.60, p < 0.005). DISCUSSION: The figure-of-8 coil may have better applicability in patients, due to the lower incidence of lack of inhibition in healthy subjects, and the lower experience of pain or discomfort

GiViP: A Visual Profiler for Distributed Graph Processing Systems

Analyzing large-scale graphs provides valuable insights in different application scenarios. While many graph processing systems working on top of distributed infrastructures have been proposed to deal with big graphs, the tasks of profiling and debugging their massive computations remain time consuming and error-prone. This paper presents GiViP, a visual profiler for distributed graph processing systems based on a Pregel-like computation model. GiViP captures the huge amount of messages exchanged throughout a computation and provides an interactive user interface for the visual analysis of the collected data. We show how to take advantage of GiViP to detect anomalies related to the computation and to the infrastructure, such as slow computing units and anomalous message patterns.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Top research priorities in healthcare-associated infection in the UK

Background: There is a mismatch between research questions which are considered to be important by patients, carers and healthcare professionals and the research performed in many fields of medicine. No relevant studies which have assessed research priorities in healthcare-associated infection (HCAI) that have involved patients' and carers' opinions were identified in the literature. / Aim: The Healthcare-Associated Infections Priority Setting Partnership was established to identify the top research priorities in the prevention, diagnosis and treatment of HCAI in the UK, considering the opinions of all these groups. / Methods: The methods broadly followed the principles of the James Lind Alliance (JLA) priority setting activity. / Findings: In total, 259 unique valid research questions were identified from 221 valid responses to a consultation of patients, carers and healthcare professionals after seeking their opinions for research priorities. The steering committee of the priority setting partnership rationalized these to 50 unique questions. A literature review established that for these questions there were no recent high-quality systematic reviews, high-quality systematic reviews which concluded that further studies were necessary, or the steering committee considered that further research was required despite the conclusions of recent systematic reviews. An interim survey ranked the 50 questions, and the 10 main research priorities were identified from the top 32 questions by consensus at a final priority setting workshop of patients, carers and healthcare professionals using group discussions. / Conclusions: A priority setting process using JLA methods and principles involving patients, carers and healthcare professionals was used to identify the top 10 priority areas for research related to HCAI. Basic, translational, clinical and public health research would be required to address these uncertainties