Corticospinal excitability changes following blood flow restriction training of the tibialis anterior: a preliminary study

© 2017 The Authors Aim To examine the neural excitability of projections to the tibialis anterior (TA) following blood flow restriction training (BFRT). This is the first study to examine the TA following BFRT. Methods Ten subjects performed each experiment. Experiment one consisted of BFRT at 130 mmHg (BFRT-low). Experiment two consisted of BFRT at 200 mmHg (BFRT-high), training (TR-only) and blood flow restriction at 200 mmHg (BFR-only) performed on separate days. Blood flow restriction was applied to the thigh and training consisted of rapid dorsiflexion contractions against gravity every 10 s for 15-min. The motor evoked potential (MEP) peak-to-peak amplitudes were recorded pre-intervention and 1-, 10-, 20- and 30-min post-intervention and expressed relative to the maximal peak-to-peak M-wave at each time-point. Results Experiment one revealed no difference in MEP amplitudes for BFRT-low over time (P = 0.09). Experiment two revealed a significant effect of time (P < 0.001), with 1-min post-intervention MEP amplitudes significantly facilitated compared to pre-intervention, but no effect of intervention (P = 0.79) or intervention*time interaction (P = 0.25). Post-hoc power calculations were performed for the intervention*time interaction. Discussion and conclusions Corticospinal excitability of projections to the TA did not change following BFRT-low and corticospinal excitability changes between BFRT-high, BFR-only and TR-only interventions were not different over time. In experiment two, there was a significant main effect of time 1-min post-intervention which was mainly due to the BFRT-high intervention. Post-hoc power calculations revealed that 15 subjects were required for a significant interaction effect 80% of the time however, as the changes in corticospinal excitability were not prolonged, a new dataset of ≥ 15 subjects was not acquired

Interaction of the CERN Large Hadron Collider (LHC) Beam with Carbon Collimators

The LHC will operate at an energy of 7 TeV with a luminosity of 1034cm-2s-1. This requires two beams, each with 2808 bunches. The energy stored in each beam of 362 MJ. In a previous paper the mechanisms causing equipment damage in case of a failure of the machine protection system was discussed, assuming that the entire beam is deflected into a copper target [1, 2]. Another failure scenario is the deflection of beam into carbon material. Carbon collimators and beam absorbers are installed in many locations around the LHC to diffuse or absorb beam losses. Since the collimator jaws are close to the beam, it is very likely that they are hit first when the beam is accidentally deflected. Here we present the results of two-dimensional hydrodynamic simulations of the heating of a solid carbon cylinder irradiated by the LHC beam with nominal parameters, carried out using the BIG-2 computer code [3] while the energy loss of the 7 TeV protons in carbon is calculated using the well known FLUKA code [4]. Our calculations suggest that the LHC beam may penetrate up to about 10 m to 15 m in solid carbon, resulting in a substantial damage of collimators and beam absorbers

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Physical, chemical and kinetic factors affecting prion infectivity

The mouse-adapted scrapie prion strain RML is one of the most widely used in prion research. The introduction of a cell culture-based assay of RML prions, the scrapie cell assay (SCA) allows more rapid and precise prion titration. A semi-automated version of this assay (ASCA) was applied to explore a range of conditions that might influence the infectivity and properties of RML prions. These include resistance to freeze-thaw procedures; stability to endogenous proteases in brain homogenate despite prolonged exposure to varying temperatures; distribution of infective material between pellet and supernatant after centrifugation, the effect of reducing agents and the influence of detergent additives on the efficiency of infection. Apparent infectivity is increased significantly by interaction with cationic detergents. Importantly, we have also elucidated the relationship between the duration of exposure of cells to RML prions and the transmission of infection. We established that the infection process following contact of cells with RML prions is rapid and followed an exponential time course, implying a single rate-limiting process

MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

Inverse analysis of critical current density in a bulk high-temperature superconducting undulator

In order to optimise the design of undulators using high-temperature superconductor (HTS) bulks we have developed a method to estimate the critical current density (Jc) of each bulk from the overall measured magnetic field of an undulator. The vertical magnetic field was measured along the electron-beam axis in a HTS bulk-based undulator consisting of twenty Gd-Ba-Cu-O (GdBCO) bulks inserted in a 12-T solenoid. The Jc values of the bulks were estimated by an inverse analysis approach in which the magnetic field was calculated by the forward simulation of the shielding currents in each HTS bulk with a given Jc. Subsequently the Jc values were iteratively updated using the pre-calculated response matrix of the undulator magnetic field to Jc. We demonstrate that it is possible to determine the Jc of each HTS bulk with sufficient accuracy for practical application within around 10 iterations. The pre-calculated response matrix, created in advance, enables the inverse analysis to be performed within a practically short time, on the order of several hours. The measurement error, which destroys the uniqueness of the solution, was investigated and the points to be noted for future magnetic field measurements were clarified. The results show that this inverse-analysis method allows the estimation of the Jc of each bulk comprising an HTS bulk undulator.CHART (Swiss Accelerator Research and Technology Collaboration); EPSRC Early Career Fellowship, EP/P020313/

Gap junctions regulate vessel diameter in chick chorioallantoic membrane vasculature by both tone‐dependent and structural mechanisms

Objective: In this study, we examined the impact of gap junction blockade on chick chorioallantoic membrane microvessels. Methods: Expression of Cx37, Cx40/42, and Cx43 in chick chorioallantoic membrane tissue was studied by PCR, Western blot, and confocal immunofluorescence microscopy. Vessel diameter changes occurring under gap junction blockade with carbenoxolone (175 µmol/L), palmitoleic acid (100 µmol/L), 43GAP27 (1 mmol/L) were analyzed by intravital microscopy. To analyze vascular tone, chick chorioallantoic membrane vessels were exposed to a vasodilator cocktail consisting of acetylcholine (10 μmol/L), adenosine (100 μmol/L), papaverine (200 μmol/L), and sodium nitroprusside (10 μmol/L). Results: In chick chorioallantoic membrane lysates, Western blot analysis revealed the expression of Cx40 and Cx43. Immunofluorescence in intact chick chorioallantoic membrane vasculature showed only Cx43, limited to arterial vessel walls. Upon gap junction blockade (3 hours) arterial and venous diameters decreased to 0.50 ± 0.03 and 0.36 ± 0.06 (carbenoxolone), 0.72 ± 0.08 and 0.63 ± 0.15 (palmitoleic acid) and 0.77 ± 0.004 and 0.58 ± 0.05 (GAP27), relative to initial values. Initially, diameter decrease was dominated by increasing vascular tone. After 6 hours, however, vessel tone was reduced, suggesting structural network remodeling. Conclusions: Our findings suggest a major role for connexins in mediating acute and chronic diameter changes in developing vascular networks

The Age of the Galactic Disk

I review different methods devised to derive the age of the Galactic Disk, namely the Radio-active Decay (RD), the Cool White Dwarf Luminosity Function (CWDLF), old opne clusters (OOC) and the Color Magnitude Diagram (CMD) of the stars in the solar vicinity. I argue that the disk is likely to be 8-10 Gyr old. Since the bulk of globulars has an age around 13 Gyr, the possibility emerges that the Galaxy experienced a minimum of Star Formation at the end of the halo/bulge formation. This minimum might reflect the time at which the Galaxy started to acquire material to form the disk inside-out.Comment: 10 pages, 4 figure, invited review, in "The chemical evolution of the Milky Way : Stars vs Clusters, Vulcano (Italy), 20-24 September 199

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations