In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis

OBJECTIVE: Hypokalaemic periodic paralysis (HypoPP) is caused by mutations of Cav1.1, and Na_{v}1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Nav1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo. METHODS: MVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP(n = 7), HypoPP (n = 10), and normal controls (n = 26). RESULTS: Muscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges. CONCLUSIONS: The in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita. SIGNIFICANCE: MVRCs provide important in vivo data that complements expression studies of ion channel mutations

Application of genomic and quantitative genetic tools to identify candidate resistance genes for brown rot resistance in peach.

The availability of a complete peach genome assembly and three different peach genome sequences created by our group provide new opportunities for application of genomic data and can improve the power of the classical Quantitative Trait Loci (QTL) approaches to identify candidate genes for peach disease resistance. Brown rot caused by Monilinia spp., is the most important fungal disease of stone fruits worldwide. Improved levels of peach fruit rot resistance have been identified in some cultivars and advanced selections developed in the UC Davis and USDA breeding programs. Whole genome sequencing of the Pop-DF parents lead to discovery of high-quality SNP markers for QTL genome scanning in this experimental population. Pop-DF created by crossing a brown rot moderately resistant cultivar 'Dr. Davis' and a brown rot resistant introgression line, 'F8,1-42', derived from an initial almond × peach interspecific hybrid, was evaluated for brown rot resistance in fruit of harvest maturity over three seasons. Using the SNP linkage map of Pop-DF and phenotypic data collected with inoculated fruit, a genome scan for QTL identified several SNP markers associated with brown rot resistance. Two of these QTLs were placed on linkage group 1, covering a large (physical) region on chromosome 1. The genome scan for QTL and SNP effects predicted several candidate genes associated with disease resistance responses in other host-pathogen systems. Two potential candidate genes, ppa011763m and ppa026453m, may be the genes primarily responsible for M. fructicola recognition in peach, activating both PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI) responses. Our results provide a foundation for further genetic dissection, marker assisted breeding for brown rot resistance, and development of peach cultivars resistant to brown rot

Array-conditioned deconvolution of multiple component teleseismic recordings

We investigate the applicability of an array-conditioned deconvolution technique, developed for analyzing borehole seismic exploration data, to teleseismic receiver functions and data preprocessing steps for scattered wavefield imaging. This multichannel deconvolution technique constructs an approximate inverse filter to the estimated source signature by solving an overdetermined set of deconvolution equations, using an array of receivers detecting a common source. We find that this technique improves the efficiency and automation of receiverfunction calculation and data preprocessing workflow. We apply this technique to synthetic experiments and to teleseismic data recorded in a dense array in northern Canada. Our results show that this optimal deconvolution automatically determines and subsequently attenuates the noise from data, enhancing P-to-S converted phases in seismograms with various noise levels. In this context, the array-conditioned deconvolution presents a new, effective and automatic means for processing large amounts of array data, as it does not require any ad-hoc regularization; the regularization is achieved naturally by using the noise present in the array itself

New Phases of Near-Extremal Branes on a Circle

We study the phases of near-extremal branes on a circle, by which we mean near-extremal branes of string theory and M-theory with a circle in their transverse space. We find a map that takes any static and neutral Kaluza-Klein black hole, i.e. any static and neutral black hole on Minkowski-space times a circle M^d x S^1, and map it to a corresponding solution for a near-extremal brane on a circle. The map is derived using first a combined boost and U-duality transformation on the Kaluza-Klein black hole, transforming it to a solution for a non-extremal brane on a circle. The resulting solution for a near-extremal brane on a circle is then obtained by taking a certain near-extremal limit. As a consequence of the map, we can transform the neutral non-uniform black string branch into a new non-uniform phase of near-extremal branes on a circle. Furthermore, we use recently obtained analytical results on small black holes in Minkowski-space times a circle to get new information about the localized phase of near-extremal branes on a circle. This gives in turn predictions for the thermal behavior of the non-gravitational theories dual to these near-extremal branes. In particular, we give predictions for the thermodynamics of supersymmetric Yang-Mills theories on a circle, and we find a new stable phase of (2,0) Little String Theory in the canonical ensemble for temperatures above its Hagedorn temperature.Comment: 72 pages, 5 figures. v2: Typos fixed, refs. added. v3: Sec. 3.2 fixe

Improving Empathy in Healthcare Consultations-a Secondary Analysis of Interventions.

A recent systematic review of randomised trials suggested that empathic communication improves patient health outcomes. However, the methods for training healthcare practitioners (medical professionals; HCPs) in empathy and the empathic behaviours demonstrated within the trials were heterogeneous, making the evidence difficult to implement in routine clinical practice. In this secondary analysis of seven trials in the review, we aimed to identify (1) the methods used to train HCPs, (2) the empathy behaviours they were trained to perform and (3) behaviour change techniques (BCTs) used to encourage the adoption of those behaviours. This detailed understanding of interventions is necessary to inform implementation in clinical practice. We conducted a content analysis of intervention descriptions, using an inductive approach to identify training methods and empathy behaviours and a deductive approach to describe the BCTs used. The most commonly used methods to train HCPs to enhance empathy were face-to-face training (n = 5), role-playing (n = 3) and videos (self or model; n = 3). Duration of training was varied, with both long and short training having high effect sizes. The most frequently targeted empathy behaviours were providing explanations of treatment (n = 5), providing non-specific empathic responses (e.g. expressing understanding) and displaying a friendly manner and using non-verbal behaviours (e.g. nodding, leaning forward, n = 4). The BCT most used to encourage HCPs to adopt empathy behaviours was "Instruction on how to perform behaviour" (e.g. a video demonstration, n = 5), followed by "Credible source" (e.g. delivered by a psychologist, n = 4) and "Behavioural practice" (n = 3 e.g. role-playing). We compared the effect sizes of studies but could not extrapolate meaningful conclusions due to high levels of variation in training methods, empathy skills and BCTs. Moreover, the methods used to train HCPs were often poorly described which limits study replication and clinical implementation. This analysis of empathy training can inform future research, intervention reporting standards and clinical practice

Cosmology of intersecting brane world models in Gauss-Bonnet gravity

We study the cosmological properties of a codimension two brane world that sits at the intersection between two four branes, in the framework of six dimensional Einstein-Gauss-Bonnet gravity. Due to contributions of the Gauss-Bonnet terms, the junction conditions require the presence of localized energy density on the codimension two defect. The induced metric on this surface assumes a FRW form, with a scale factor associated to the position of the brane in the background; we can embed on the codimension two defect the preferred form of energy density. We present the cosmological evolution equations for the three brane, showing that, for the case of pure AdS$_6$ backgrounds, they acquire the same form of the ones for the Randall-Sundrum II model. When the background is different from pure AdS$_6$, the cosmological behavior is potentially modified in respect to the typical one of codimension one brane worlds. We discuss, in a particular model embedded in an AdS$_6$ black hole, the conditions one should satisfy in order to obtain standard cosmology at late epochs.Comment: 19 pages, no figures, JHEP style. v2: Typos corrected and references adde

Excitability Properties of Mouse and Human Skeletal Muscle Fibres Compared by Muscle Velocity Recovery Cycles.

Mouse models of skeletal muscle channelopathies are not phenocopies of human disease. In some cases (e.g. Myotonia Congenita) the phenotype is much more severe, whilst in others (e.g. Hypokalaemic periodic paralysis) rodent physiology is protective. This suggests a species' difference in muscle excitability properties. In humans these can be measured indirectly by the post-impulse changes in conduction velocity, using Muscle Velocity Recovery Cycles (MVRCs). We performed MVRCs in mice and compared their muscle excitability properties with humans. Mouse Tibialis Anterior MVRCs (n = 70) have only one phase of supernormality (increased conduction velocity), which is smaller in magnitude (p = 9 × 10-21), and shorter in duration (p = 3 × 10-24) than human (n = 26). This abbreviated supernormality is followed by a period of late subnormality (reduced velocity) in mice, which overlaps in time with the late supernormality seen in human MVRCs. The period of late subnormality suggests increased t-tubule Na+/K+-pump activity. The subnormal phase in mice was converted to supernormality by blocking ClC-1 chloride channels, suggesting relatively higher chloride conductance in skeletal muscle. Our findings help explain discrepancies in phenotype between mice and humans with skeletal muscle channelopathies and potentially other neuromuscular disorders. MVRCs are a valuable new tool to compare in vivo muscle membrane properties between species and will allow further dissection of the molecular mechanisms regulating muscle excitability

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

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

Evaluating the utility of B/Ca ratios in planktic foraminifera as a proxy for the carbonate system: A case study of Globigerinoides ruber

B/Ca ratios in foraminifera have attracted considerable scientific attention as a proxy for past ocean carbonate system. However, the carbonate system controls on B/Ca ratios are not straightforward, with ?[ inline image] ([ inline image]in situ – [ inline image]at saturation) correlating best with B/Ca ratios in benthic foraminifera, rather than pH, inline image, or inline image (as a simple model of boron speciation in seawater and incorporation into CaCO3 would predict). Furthermore, culture experiments have shown that in planktic foraminifera properties such as salinity and [B]sw can have profound effects on B/Ca ratios beyond those predicted by simple partition coefficients. Here, we investigate the controls on B/Ca ratios in G. ruber via a combination of culture experiments and core-top measurements, and add to a growing body of evidence that suggests B/Ca ratios in symbiont-bearing foraminiferal carbonate are not a straightforward proxy for past seawater carbonate system conditions. We find that while B/Ca ratios in culture experiments covary with pH, in open ocean sediments this relationship is not seen. In fact, our B/Ca data correlate best with [ inline image] (a previously undocumented association) and in most regions, salinity. These findings might suggest a precipitation rate or crystallographic control on boron incorporation into foraminiferal calcite. Regardless, our results underscore the need for caution when attempting to interpret B/Ca records in terms of the ocean carbonate system, at the very least in the case of mixed-layer planktic foraminifera