Fatigue induced changes to kinematic and kinetic gait parameters following six minutes of walking in people with Multiple Sclerosis

This is an Accepted Manuscript of an article published by Taylor & Francis in Disability and Rehabilitation on 20 May 2015, available online: http://www.tandfonline.com/doi/abs/10.3109/09638288.2015.1047969Purpose: The aim of this study was to examine the effect of 6 min of walking on fatigue, exertion and spatiotemporal, kinematic and kinetic gait parameters in people with multiple sclerosis (MS). Methods: Thirty-four people with MS with moderate levels of disability completed measures of fatigue, exertion and instrumented gait analysis before and after 6-min trials of rest and walking (using a modified 6-min walk test, m6MWT). Ten age- and gender-matched healthy controls completed analysis before and after the m6MWT. Results: The MS group had a significant increase in self-reported fatigue following the m6MWT; however, there was no effect on spatiotemporal gait parameters. During stance on the more affected side ankle dorsiflexion at initial contact decreased, while knee and hip flexor moments and hip power absorption increased. On the less affected side ankle and knee power absorption, and hip extensor moment all increased. Healthy controls showed increases in joint kinetics likely due to increased walking speeds following m6MWT. Conclusion: For people with MS, ankle dorsiflexion angle reduces at initial contact following walking induced fatigue, while increased power absorption at the hip, knee and ankle indicate gait inefficiencies that may contribute to higher levels of fatigue and exertion. Implications for Rehabilitation The modified 6-min walk test (m6MWT) leads to significant increases in self-reported fatigue and exertion in people with MS. Following the m6MWT, there is significantly reduced ankle dorsiflexion angle at initial contact in the more affected leg in people with MS. This reveals an important walking-induced kinematic change that should be the target of future orthotic and strengthening interventions. In people with MS, increased power absorption primarily during the stance phase of gait following the m6MWT reveals important walking-induced muscle weakness that should also be monitored in future strengthening and gait retraining interventions

Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites

Autoantibodies to insulin are a harbinger of autoimmunity in type 1 diabetes in humans and in non-obese diabetic mice. To understand the genesis of these autoantibodies, we investigated the interactions of insulin-specific T and B lymphocytes using T cell and B cell receptor transgenic mice. We found spontaneous anti-insulin germinal center (GC) formation throughout lymphoid tissues with GC B cells binding insulin. Moreover, because of the nature of the insulin epitope recognized by the T cells, it was evident that GC B cells presented a broader repertoire of insulin epitopes. Such broader recognition was reproduced by activating naive B cells ex vivo with a combination of CD40 ligand and interleukin 4. Thus, insulin immunoreactivity extends beyond the pancreatic lymph node–islets of Langerhans axis and indicates that circulating insulin, despite its very low levels, can have an influence on diabetogenesis

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Does the small CMB quadrupole moment suggest new physics?

Motivated by WMAP's confirmation of an anomalously low value of the quadrupole moment of the CMB temperature fluctuations, we investigate the effects on the CMB of cutting off the primordial power spectrum P(k) at low wave numbers. This could arise, for example, from a break in the inflaton potential, a prior period of matter or radiation domination, or an oscillating scalar field which couples to the inflaton. We reanalyze the full WMAP parameter space supplemented by a low-k cutoff for P(k). The temperature correlations by themselves are better fit by a cutoff spectrum, but including the TE temperature-polarization spectrum reduces this preference to a 1.4 sigma effect. Inclusion of large scale structure data does not change the conclusion. If taken seriously, the low-k cutoff is correlated with optical depth so that reionization occurs even earlier than indicated by the WMAP analysis.Comment: 10 pages 6 figures; corrected eq. 4.1; clarified discussion explaining apparent discrepancy with WMAP's estimate of low quadrupole significanc

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.Koronis Pharmaceutical