Disruption of sitting balance after stroke: influence of spoken output

Objectives: To identify the extent of dual task interference between cognitive and motor tasks, (cognitive motor interference (CMI)) in sitting balance during recovery from stroke; to compare CMI in sitting balance between stroke and non-stroke groups; and to record any changes to CMI during sitting that correlate with functional recovery. Method: 36 patients from stroke rehabilitation settings in three NHS trusts. Healthy control group: 21 older volunteers. Measures of seated postural sway were taken in unsupported sitting positions, alone, or concurrently with either a repetitive utterance task or an oral word category generation task. Outcome measures were variability of sway area, path length of sway, and the number of valid words generated. Results: Stroke patients were generally less stable than controls during unsupported sitting tasks. They showed greater sway during repetitive speech compared with quiet sitting, but did not show increased instability to posture between repetitive speech and word category generation. When compared with controls, stroke patients experienced greater dual task interferences during repetitive utterance but not during word generation. Sway during repetitive speech was negatively correlated with concurrent function on the Barthel ADL index. Conclusions: The stroke patients showed postural instability and poor word generation skills. The results of this study show that the effort of verbal utterances alone was sufficient to disturb postural control early after stroke, and the extent of this instability correlated with concomitant Barthel ADL function.

The effect of the GENTLE/s robot-mediated therapy system on arm function after stroke

Objective: To evaluate the effect of robot-mediated therapy on arm dysfunction post stroke. Design: A series of single-case studies using a randomized multiple baseline design with ABC or ACB order. Subjects (n = 20) had a baseline length of 8, 9 or 10 data points. They continued measurement during the B - robot-mediated therapy and C - sling suspension phases. Setting: Physiotherapy department, teaching hospital. Subjects: Twenty subjects with varying degrees of motor and sensory deficit completed the study. Subjects attended three times a week, with each phase lasting three weeks. Interventions: In the robot-mediated therapy phase they practised three functional exercises with haptic and visual feedback from the system. In the sling suspension phase they practised three single-plane exercises. Each treatment phase was three weeks long. Main measures: The range of active shoulder flexion, the Fugl-Meyer motor assessment and the Motor Assessment Scale were measured at each visit. Results: Each subject had a varied response to the measurement and intervention phases. The rate of recovery was greater during the robot-mediated therapy phase than in the baseline phase for the majority of subjects. The rate of recovery during the robot-mediated therapy phase was also greater than that during the sling suspension phase for most subjects. Conclusion: The positive treatment effect for both groups suggests that robot-mediated therapy can have a treatment effect greater than the same duration of non-functional exercises. Further studies investigating the optimal duration of treatment in the form of a randomized controlled trial are warranted.

Speech therapy after stroke: trial shows only that practice varies

Bowen and colleagues’ methods and conclusions raise concerns.1 At best, the trial evaluates the variability in current practice. In no way is it a robust test of treatment. Two communication impairments (aphasia and dysarthria) were included. In the post-acute stage spontaneous recovery is highly unpredictable, and changes in the profile of impairment during this time are common.2 Both impairments manifest in different forms,3 which may be more or less responsive to treatment. A third kind of impairment, apraxia of speech, was not excluded but was not targeted in therapy. All three impairments can and do co-occur. Whether randomised controlled trial designs can effectively cope with such complex disorders has been discussed elsewhere.4 Treatment was defined within terms of current practice but was unconstrained. Therefore, the treatment group would have received a variety of therapeutic approaches and protocols, some of which may indeed be ineffective. Only 53% of the contact time with a speech and language therapist was direct (one to one), the rest was impairment based therapy. In contrast, all of the visitors’ time was direct contact, usually in conversation. In both groups, the frequency and length of contact time varied. We already know that the transfer from impairment based therapy to functional communication can be limited and varies across individuals.5 However, it is not possible to conclude from this trial that one to one impairment based therapy should be replaced. For that, a well defined impairment therapy protocol must be directly compared with a similarly well defined functional communication therapy, with an attention control.

Effect of acyl chain length on transfection efficiency and toxicity of polyethylenimine

Polyethylenimine (PEI) is an efficient nonviral gene delivery vector because of its high buffering capacity and DNA condensation ability. In our study, the amino groups on the polymeric backbone were acylated using acetic or propionic anhydride to alter the protonation behaviour and the hydrophilic/hydrophobic balance of the polymer. The concentration of acylated primary amines was determined using trinitrobenzene sulphonic acid assay. Results showed that our modified polymers had lower buffering capacities in solutions compared to PEI. The polymers were complexed with plasmid encoding enhanced green fluorescent protein at three different ratios (1:1, 1:2 and 1:10 w/w DNA to polymer) to form polyplexes and their toxicities and transfection efficiencies were evaluated in HEK 293 cells. Acylation reduced the number of primary amines on the polymer and the surface charge, improving haemocompatibility and reducing cytotoxicity. The reduction in the concentration of amino groups helped to optimise DNA compaction and facilitated polyplex dissociation in the cell, which increased transfection efficiency of the modified polymers compared to the parent polymer. Polymers with buffering capacities greater than 50% and less than 80% relative to PEI, showed higher transfection efficiencies than PEI. The propionic anhydride modified polymers had appropriate interactions with DNA which provided both DNA compaction and polyplex dissociation. These systems interacted better with the cell membrane because of their slightly higher lipophilicity and formed polyplexes which were less cytotoxic than polyplexes of acetic anhydride modified polymers. Among the vectors tested, 1:0.3 mol/mol PEI:propionic anhydride in a 1:2 w/w DNA:polymer composition provided the best transfection system with improved transfection efficiency and reduced cytotoxicity.

The relationships of age and length of service with job satisfaction: an examination of hotel employees in Thailand

Earlier studies suggest age is positively associated with job satisfaction, while others use length of service, or tenure, as a predictor of job satisfaction levels. This article examines whether age and tenure are individual determinants of satisfaction, or whether there is an interaction between the two. The results indicate that employee age is not significantly associated with overall job satisfaction level, but that tenure is. There is also significant relationship between tenure and facets of satisfaction (job, pay and fringe benefits), but the effect of tenure on satisfaction is significantly modified by age.

How a sequential design would have affected the GAIN international study of Gavestinel in stroke

While planning the GAIN International Study of gavestinel in acute stroke, a sequential triangular test was proposed but not implemented. Before the trial commenced it was agreed to evaluate the sequential design retrospectively to evaluate the differences in the resulting analyses, trial durations and sample sizes in order to assess the potential of sequential procedures for future stroke trials. This paper presents four sequential reconstructions of the GAIN study made under various scenarios. For the data as observed, the sequential design would have reduced the trial sample size by 234 patients and shortened its duration by 3 or 4 months. Had the study not achieved a recruitment rate that far exceeded expectation, the advantages of the sequential design would have been much greater. Sequential designs appear to be an attractive option for trials in stroke. Copyright 2004 S. Karger AG, Basel

Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline

The International Citicoline Trial in acUte Stroke is a sequential phase III study of the use of the drug citicoline in the treatment of acute ischaemic stroke, which was initiated in 2006 in 56 treatment centres. The primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow-up. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well-established scales: the Barthel Index, the modified Rankin scale and the National Institutes of Health Stroke Scale. This approach was previously used in the analysis of the influential National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator in stroke. The purpose of this paper is to describe how this trial was designed, and in particular how the simultaneous objectives of taking into account three assessment scales, performing a series of interim analyses and conducting treatment allocation and adjusting the analyses to account for prognostic factors, including more than 50 treatment centres, were addressed. Copyright (C) 2008 John Wiley & Sons, Ltd.

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)

An approximate Bayesian computation approach to overcome biases that arise when using amplified fragment length polymorphism markers to study population structure

There is great interest in using amplified fragment length polymorphism (AFLP) markers because they are inexpensive and easy to produce. It is, therefore, possible to generate a large number of markers that have a wide coverage of species genotnes. Several statistical methods have been proposed to study the genetic structure using AFLP's but they assume Hardy-Weinberg equilibrium and do not estimate the inbreeding coefficient, F-IS. A Bayesian method has been proposed by Holsinger and colleagues that relaxes these simplifying assumptions but we have identified two sources of bias that can influence estimates based on these markers: (i) the use of a uniform prior on ancestral allele frequencies and (ii) the ascertainment bias of AFLP markers. We present a new Bayesian method that avoids these biases by using an implementation based on the approximate Bayesian computation (ABC) algorithm. This new method estimates population-specific F-IS and F-ST values and offers users the possibility of taking into account the criteria for selecting the markers that are used in the analyses. The software is available at our web site (http://www-leca.uif-grenoble.fi-/logiciels.htm). Finally, we provide advice on how to avoid the effects of ascertainment bias.

Amplified fragment length polymorphism genetic fingerprinting challenges the taxonomic status of the near-endemic species Chara curta Nolte ex Kutz. (Characeae)

Amplified fragment length polymorphism (AFLP) genetic fingerprinting of 14 accessions of Chara curta and Chara aspera Willd., sampled across a range of habitats and morphologies in Britain, suggests that these taxa are part of the variation within a single species complex. Two primer combinations generating 397 fragments (97% of which were polymorphic), analysed by Jaccard's similarity coefficient and principal co-ordinate analysis, did not recover groups which reflect the current taxonomy. By contrast with the genetic study, a Gower general similarity coefficient and principal co-ordinate analysis of 52 morphological characters recovered the currently recognized species groups. A Mantel test showed no significant correlation between the genetic data and the morphological data, supporting the hypothesis that phenotypic variability in Chara L. is either to some extent environmentally induced or represents developmental stages. Implications for the conservation status of C. curta in Britain are discussed. (c) 2007 The Linnean Society of London, Botanical Journal of the Linnean Society, 2007, 155, 467-476.

Analysis of the antigen combining site: Correlations between length and sequence composition of the hypervariable loops and the nature of the antigen

It has long been suggested that the overall shape of the antigen combining site (ACS) of antibodies is correlated with the nature of the antigen. For example, deep pockets are characteristic of antibodies that bind haptens, grooves indicate peptide binders, while antibodies that bind to proteins have relatively flat combining sites. In. 1996, MacCallum, Martin and Thornton used a fractal shape descriptor and showed a strong correlation of the shape of the binding region with the general nature of the antigen. However, the shape of the ACS is determined primarily by the lengths of the six complementarity-determining regions (CDRs). Here, we make a direct correlation between the lengths of the CDRs and the nature of the antigen. In addition, we show significant differences in the residue composition of the CDRs of antibodies that bind to different antigen classes. As well as helping us to understand the process of antigen recognition, autoimmune disease and cross-reactivity these results are of direct application in the design of antibody phage libraries and modification of affinity. (C) 2003 Elsevier Science Ltd. All rights reserved.

Acute stroke predisposes to oral gram-negative bacilli - a cause of aspiration pneumonia?

Objectives: To assess any change in the oral flora in the mouths of stroke patients during the acute and rehabilitation phases and to determine whether this is related to episodes of aspiration pneumonia and clinical outcome. Materials and Methods: This observational study was carried out in hospital wards in a University teaching hospital. The subjects were patients immediately post-stroke and during the rehabilitation period, acute admissions and a group of healthy volunteers. An assessment of dentition and swallow in the presence or absence of oral aerobic gram-negative bacilli (AGNB) was correlated. Results: Of the acute stroke patients 52% had an unsafe swallow. AGNB carriage was documented in 34% of the acute stroke group. Of the 11 patients who died 55% had AGNB, 73% had an unsafe swallow and 36% had a combination of both. Conclusion: AGNB is a common finding in acute stroke patients. It is not a consequence of age or acute hospitalisation and is associated with an unsafe swallow and a higher mortality. Copyright (C) 2003 S. Karger AG, Basel.