Background and purpose
In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more ...improvement in patients receiving immune globulin (IGIV‐C) intravenously than in those receiving placebo.
Methods
We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP.
Results
A randomized double‐blind trial was undertaken in 117 CIDP patients who received IGIV‐C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut‐off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV‐C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV‐C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV‐C group (37.5%–50.9%) than in the placebo group (21.1%–25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1‐point deterioration) findings.
Conclusions
Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.
Click here to view the accompanying paper in this issue.
Background and purpose
Charcot‐Marie‐Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains ...fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT‐TRIAAL/CMT‐TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A.
Methods
Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot–Marie−Tooth Examination Score (CMTES).
Results
NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES.
Conclusions
This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length‐dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.
Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been ...published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).
Dynamic causal modelling (DCM) of functional magnetic resonance imaging (fMRI) data offers new insights into the pathophysiology of neurological disease and mechanisms of effective therapies. Current ...applications can be used both to identify the most likely functional brain network underlying observed data and estimate the networks' connectivity parameters. We examined the reproducibility of DCM in healthy subjects (young 18–48 years, n=27; old 50–80 years, n=15) in the context of action selection. We then examined the effects of Parkinson's disease (50–78 years, Hoehn and Yahr stage 1–2.5, n=16) and dopaminergic therapy. Forty-eight models were compared, for each of 90 sessions from 58 subjects. Model-evidences clustered according to sets of structurally similar models, with high correlations over two sessions in healthy older subjects. The same model was identified as most likely in healthy controls on both sessions and in medicated patients. In this most likely network model, the selection of action was associated with enhanced coupling between prefrontal cortex and the pre-supplementary motor area. However, the parameters for intrinsic connectivity and contextual modulation in this model were poorly correlated across sessions. A different model was identified in patients with Parkinson's disease after medication withdrawal. In “off” patients, action selection was associated with enhanced connectivity from prefrontal to lateral premotor cortex. This accords with independent evidence of a dopamine-dependent functional disconnection of the SMA in Parkinson's disease. Together, these results suggest that DCM model selection is robust and sensitive enough to study clinical populations and their pharmacological treatment. For critical inferences, model selection may be sufficient. However, caution is required when comparing groups or drug effects in terms of the connectivity parameter estimates, if there are significant posterior covariances among parameters.
Clostridial infection of the intestine can result in necrotic enteritis (NE), compromising production and health of poultry. Mucins play a major role in protecting the intestinal epithelium from ...infection. The relative roles of different mucins in gut pathology following bacterial challenge are unclear. This study was designed to quantify the expression of mucin and mucin-related genes, using intestinal samples from an NE challenge trial where birds were fed diets with or without in-feed antimicrobials. A method for quantifying mucin gene expression was established using a suite of reference genes to normalize expression data. This method was then used to quantify the expression of 11 candidate genes involved in mucin, inflammatory cytokine, or growth factor biosynthesis (IL-18, KGF, TLR4, TFF2, TNF-α, MUC2, MUC4, MUC5ac, MUC5b, MUC13, and MUC16). The only genes that were differentially expressed in the intestine among treatment groups were MUC2, MUC13, and MUC5ac. Expression of MUC2 and MUC13 was depressed by co-challenge with Eimeria spp. and Clostridium perfringens. Antimicrobial treatment prevented an NE-induced decrease in MUC2 expression but did not affect MUC13. The expression of MUC5ac was elevated in birds challenged with Eimeria spp./C. perfringens compared with unchallenged controls and antimicrobial treatment. Changes to MUC gene expression in challenged birds is most likely a consequence of severe necrosis of the jejunal mucosa.
We investigate the properties of the galaxies selected from the deepest 850-μm survey undertaken to date with (Submillimetre Common-User Bolometer Array 2) SCUBA-2 on the James Clerk Maxwell ...Telescope as part of the SCUBA-2 Cosmology Legacy Survey. A total of 106 sources (>5σ) were uncovered at 850 μm from an area of ≃150 arcmin2 in the centre of the COSMOS/UltraVISTA/Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) field, imaged to a typical depth of σ850 ≃ 0.25 mJy. We utilize the available multifrequency data to identify galaxy counterparts for 80 of these sources (75 per cent), and to establish the complete redshift distribution for this sample, yielding
$\bar{z} = 2.38\pm 0.09$
. We have also been able to determine the stellar masses of the majority of the galaxy identifications, enabling us to explore their location on the star formation rate:stellar mass (SFR:M*) plane. Crucially, our new deep 850-μm-selected sample reaches flux densities equivalent to SFR ≃ 100 M⊙ yr−1, enabling us to confirm that sub-mm galaxies form the high-mass end of the ‘main sequence’ (MS) of star-forming galaxies at z > 1.5 (with a mean specific SFR of sSFR = 2.25 ± 0.19 Gyr−1 at z ≃ 2.5). Our results are consistent with no significant flattening of the MS towards high masses at these redshifts. However, our results add to the growing evidence that average sSFR rises only slowly at high redshift, resulting in log10sSFR being an apparently simple linear function of the age of the Universe.
Anthropogenically induced global climate change has profound implications for marine ecosystems and the economic and social systems that depend upon them. The relationship between temperature and ...individual performance is reasonably well understood, and much climate-related research has focused on potential shifts in distribution and abundance driven directly by temperature. However, recent work has revealed that both abiotic changes and biological responses in the ocean will be substantially more complex. For example, changes in ocean chemistry may be more important than changes in temperature for the performance and survival of many organisms. Ocean circulation, which drives larval transport, will also change, with important consequences for population dynamics. Furthermore, climatic impacts on one or a few 'leverage species' may result in sweeping community-level changes. Finally, synergistic effects between climate and other anthropogenic variables, particularly fishing pressure, will likely exacerbate climate-induced changes. Efforts to manage and conserve living marine systems in the face of climate change will require improvements to the existing predictive framework. Key directions for future research include identifying key demographic transitions that influence population dynamics, predicting changes in the community-level impacts of ecologically dominant species, incorporating populations' ability to evolve (adapt), and understanding the scales over which climate will change and living systems will respond.
Overview of the SPARC tokamak Creely, A. J.; Greenwald, M. J.; Ballinger, S. B. ...
Journal of plasma physics,
10/2020, Letnik:
86, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak ...with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
Objectives. The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but ...is commonly discontinued due to adverse effects. Adverse effects are thought to be mediated via folate antagonism. In this paper we summarize the current data on the use of folates as a supplement to MTX use in RA for the prevention of adverse effects and as a potential modulator of cardiovascular risk, and propose guidelines for standard practice. Methods. A Medline search was performed using the search terms ‘methotrexate’, ‘folic acid’, ‘folinic acid’, ‘folate’ and ‘homocysteine’. Literature relevant to the use of folates as a supplement to MTX in the treatment of RA was reviewed and other papers referred to as references were explored. Results. The use of supplemental folates, including folic and folinic acid, in RA patients treated with MTX has been shown to improve continuation rates by reducing the incidence of liver function test abnormalities and gastrointestinal intolerance. Folate supplements do not appear to significantly reduce the effectiveness of MTX in the treatment of RA. Furthermore, supplemental folic acid offsets the elevation in plasma homocysteine associated with the use of MTX. This may in turn reduce the risk of cardiovascular disease, which is over-represented amongst patients with RA, and for which hyperhomocysteinaemia is now recognized as an independent risk factor. Conclusions. We propose that folic acid supplements be prescribed routinely to all patients receiving MTX for the treatment of RA. We recommend a pragmatic dosing schedule of 5 mg of oral folic acid given on the morning following the day of MTX administration.
Background and purpose
Cost‐of‐illness studies and health‐related quality of life (HRQoL) measurements are needed to assess the effects of chronic inflammatory demyelinating polyradiculoneuropathy ...(CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN) on society.
Methods
This study was conducted in 2008 in a southeast England population of 3 557 352 people. Data on service use and treatment were collected with a client service receipt inventory and service costs were calculated by combining these data with national unit costs. The EuroQol was used to calculate utility scores, a measurement of HRQoL.
Results
The total annual cost‐of‐illness per patient was £22 085 for CIDP, £22 812 for MMN and £7566 for PDN. The annual total cost per patient was £49 430 for individuals on intravenous immunoglobulin (IVIg) and £9046 for those not on IVIg (P < 0.01). The mean (SD) utility scores were 0.62 (0.23) for CIDP, 0.63 (0.22) for PDN and 0.72 (0.14) for MMN (P = 0.52). The mean (SD) utility score for those on IVIg was 0.65 (0.16) and those not on IVIg 0.63 (0.23) (P = 0.77).
Conclusion
The use of IVIg was the most important determinant of cost in all three diseases and the higher frequency of its use in CIDP and MMN accounted for the much greater average cost per patient in these diseases. There was no significant difference in HRQoL amongst the three diseases or between those receiving or not receiving IVIg.
PDF
