Curvature, singularities and projections of smooth maps

This work is an initial attempt to extend to many-parameter families of smooth functions on a smooth manifold, and projections of smooth maps into subspaces of higher dimension, the well-known inter relations, between the space of Morse function on a smooth manifold and the space of immersions of the manifold in a cartesian space, which are given by the Gauss-maps of the immersions, and the orthogonal projections of the immersions onto lines in the Cartesian spaces. Results, both local and global, are obtained

Representational gestures in Developmental Coordination Disorder and specific language impairment: Error-types and the reliability of ratings

Gesture production was studied in children with developmental coordination disorder (DCD) and specific language impairment (SLI) in comparison to normally developing age-matched and younger control children. The pattern of error production was investigated to characterize the praxis skills seen in these two developmental disorders as well as to inform understanding of the aetiology of both DCD and SLI. Given the subjective nature of the categorization of errors, a separate study was conducted to investigate inter-rater reliability. Independent adult raters consistently used four out of fourteen error-types and for these four, inter-rater reliability was found to be good. The type of errors made by children with DCD, SLI and the younger controls were very similar. The only difference between the groups was in the frequency with which errors were displayed, suggesting that the performance of the clinical children might be an indicator of immature praxis development. It is suggested that the inclusion of a younger control (similar to a ''motor match'') group is an important methodological device for investigating the underlying nature of disorders such as DCD and SL

The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease

Background and Aims: Recent data suggest that polymorphisms in the organic cation transporter (OCTN) genes OCTN1 (SLC22A4) and OCTN2 (SLC22A5) represent disease-causing mutations within the IBD5 locus (chromosome 5q31). We investigated associations with disease susceptibility, phenotype, and evidence for epistasis with CARD15 in 679 patients with Crohn’s disease (CD) or ulcerative colitis (UC). Methods: A total of 374 patients with CD, 305 patients with UC, and 294 healthy controls (HCs) were studied. Genotyping for single nucleotide polymorphisms IGR2096, IGR2198, and IGR2230, OCTN1 variant (SLC22A4 1672C→T), and OCTN2 variant (SLC22A5 −207G→C) was performed using the TaqMan system. Results: The IBD5 OCTN1 and OCTN2 polymorphisms were in strong linkage disequilibrium (D′, >0.959). IGR2198 variant allele frequency (49.1% vs 40.8%; P = .0046) and homozygosity (21% vs 14.8%; P = .044) were associated with CD versus HCs. Variant allelic frequency of OCTN1 (53.6% vs 43%; P = .0008) and OCTN2 (56.1% vs 48.4%; P = .0092) polymorphisms and homozygosity for the OCTN1/2-TC haplotype (28.4% vs 16%; P = .0042) were associated with CD versus HCs. IGR2198 homozygosity and TC homozygosity were associated with stricturing/penetrating disease at follow-up (P = .011 and P = .011, respectively) and disease progression (P = .038 and P = .049, respectively) on univariate analysis and with need for surgery on multivariate analysis (P = .016 and P = .004, respectively). In the absence of the IBD5 risk haplotype, no association of OCTN1/2 variants with CD was detected. No associations were seen with UC. Conclusions: The IBD5 locus influences susceptibility, progression, and need for surgery in CD. However, the contribution of OCTN1/2 variants is not independent of the IBD5 haplotype; a causative role for these genes remains plausible but is not yet proven. Further genetic, functional, and expression data are now required. </p

Representation of Instantaneous and Short-Term Loudness in the Human Cortex.

Acoustic signals pass through numerous transforms in the auditory system before perceptual attributes such as loudness and pitch are derived. However, relatively little is known as to exactly when these transformations happen, and where, cortically or sub-cortically, they occur. In an effort to examine this, we investigated the latencies and locations of cortical entrainment to two transforms predicted by a model of loudness perception for time-varying sounds: the transforms were instantaneous loudness and short-term loudness, where the latter is hypothesized to be derived from the former and therefore should occur later in time. Entrainment of cortical activity was estimated from electro- and magneto-encephalographic (EMEG) activity, recorded while healthy subjects listened to continuous speech. There was entrainment to instantaneous loudness bilaterally at 45, 100, and 165 ms, in Heschl's gyrus, dorsal lateral sulcus, and Heschl's gyrus, respectively. Entrainment to short-term loudness was found in both the dorsal lateral sulcus and superior temporal sulcus at 275 ms. These results suggest that short-term loudness is derived from instantaneous loudness, and that this derivation occurs after processing in sub-cortical structures.This work was supported by an ERC Advanced Grant (230570, ‘Neurolex’) to WMW, and by MRC Cognition and Brain Sciences Unit (CBU) funding to WMW (U.1055.04.002.00001.01). Computing resources were provided by the MRC-CBU.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fnins.2016.0018

Tracking cortical entrainment in neural activity: auditory processes in human temporal cortex.

A primary objective for cognitive neuroscience is to identify how features of the sensory environment are encoded in neural activity. Current auditory models of loudness perception can be used to make detailed predictions about the neural activity of the cortex as an individual listens to speech. We used two such models (loudness-sones and loudness-phons), varying in their psychophysiological realism, to predict the instantaneous loudness contours produced by 480 isolated words. These two sets of 480 contours were used to search for electrophysiological evidence of loudness processing in whole-brain recordings of electro- and magneto-encephalographic (EMEG) activity, recorded while subjects listened to the words. The technique identified a bilateral sequence of loudness processes, predicted by the more realistic loudness-sones model, that begin in auditory cortex at ~80 ms and subsequently reappear, tracking progressively down the superior temporal sulcus (STS) at lags from 230 to 330 ms. The technique was then extended to search for regions sensitive to the fundamental frequency (F0) of the voiced parts of the speech. It identified a bilateral F0 process in auditory cortex at a lag of ~90 ms, which was not followed by activity in STS. The results suggest that loudness information is being used to guide the analysis of the speech stream as it proceeds beyond auditory cortex down STS toward the temporal pole.This work was supported by an EPSRC grant to William D. Marslen-Wilson and Paula Buttery (EP/F030061/1), an ERC Advanced Grant (Neurolex) to William D. Marslen-Wilson, and by MRC Cognition and Brain Sciences Unit (CBU) funding to William D. Marslen-Wilson (U.1055.04.002.00001.01). Computing resources were provided by the MRC-CBU and the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/). Andrew Liu and Phil Woodland helped with the HTK speech recogniser and Russell Thompson with the Matlab code. We thank Asaf Bachrach, Cai Wingfield, Isma Zulfiqar, Alex Woolgar, Jonathan Peelle, Li Su, Caroline Whiting, Olaf Hauk, Matt Davis, Niko Kriegeskorte, Paul Wright, Lorraine Tyler, Rhodri Cusack, Brian Moore, Brian Glasberg, Rik Henson, Howard Bowman, Hideki Kawahara, and Matti Stenroos for invaluable support and suggestions.This is the final published version. The article was originally published in Frontiers in Computational Neuroscience, 10 February 2015 | doi: 10.3389/fncom.2015.0000

Dipy, a library for the analysis of diffusion MRI data

Diffusion Imaging in Python (Dipy) is a free and open source software projectfor the analysis of data from diffusion magnetic resonance imaging (dMRI)experiments. dMRI is an application of MRI that can be used to measurestructural features of brain white matter. Many methods have been developed touse dMRI data to model the local configuration of white matter nerve fiberbundles and infer the trajectory of bundles connecting different parts of thebrain.Dipy gathers implementations of many different methods in dMRI, including:diffusion signal pre-processing; reconstruction of diffusion distributions inindividual voxels; fiber tractography and fiber track post-processing, analysisand visualization. Dipy aims to provide transparent implementations forall the different steps of dMRI analysis with a uniform programming interface.We have implemented classical signal reconstruction techniques, such as thediffusion tensor model and deterministic fiber tractography. In addition,cutting edge novel reconstruction techniques are implemented, such asconstrained spherical deconvolution and diffusion spectrum imaging withdeconvolution, as well as methods for probabilistic tracking and originalmethods for tractography clustering. Many additional utility functions areprovided to calculate various statistics, informative visualizations, as wellas file-handling routines to assist in the development and use of noveltechniques.In contrast to many other scientific software projects, Dipy is not beingdeveloped by a single research group. Rather, it is an open project thatencourages contributions from any scientist/developer through GitHub and opendiscussions on the project mailing list. Consequently, Dipy today has aninternational team of contributors, spanning seven different academic institutionsin five countries and three continents, which is still growing

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Effects of sprint interval training on ectopic lipids and tissue-specific insulin sensitivity in men with non-alcoholic fatty liver disease

Purpose: This study examined the feasibility of sprint interval exercise training (SIT) for men with non-alcoholic fatty liver disease (NAFLD) and its effects on intrahepatic triglyceride (IHTG), insulin sensitivity (hepatic and peripheral), visceral (VAT) and subcutaneous adipose tissue (ScAT). Methods: Nine men with NAFLD (age 41 ± 8 years; BMI 31.7 ± 3.1 kg m−2; IHTG 15.6 ± 8.3%) were assessed at: (1) baseline (2) after a control phase of no intervention (pre-training) and (3) after 6 weeks of SIT (4–6 maximal 30 s cycling intervals, three times per week). IHTG, VAT and ScAT were measured using magnetic resonance spectroscopy or imaging and insulin sensitivity was assessed via dual-step hyperinsulinaemic-euglycaemic clamp with [6,6-D2] glucose tracer. Results: Participants adhered to SIT, completing ≥ 96.7% of prescribed intervals. SIT increased peak oxygen uptake [ V O2peak: + 13.6% (95% CI 8.8–18.2%)] and elicited a relative reduction in IHTG [− 12.4% (− 31.6 to 6.7%)] and VAT [− 16.9% (− 24.4 to − 9.4%); n = 8], with no change in body weight or ScAT. Peripheral insulin sensitivity increased throughout the study (n = 8; significant main effect of phase) but changes from pre- to post-training were highly variable (range − 18.5 to + 58.7%) and not significant (P = 0.09), despite a moderate effect size (g* = 0.63). Hepatic insulin sensitivity was not influenced by SIT. Conclusions: SIT is feasible for men with NAFLD in a controlled laboratory setting and is able to reduce IHTG and VAT in the absence of weight loss