Addressing unpredictability may be the key to improving performance with current clinically prescribed myoelectric prostheses.

The efferent control chain for an upper-limb myoelectric prosthesis can be separated into 3 key areas: signal generation, signal acquisition, and device response. Data were collected from twenty trans-radial myoelectric prosthesis users using their own clinically prescribed devices, to establish the relative impact of these potential control factors on user performance (user functionality and everyday prosthesis usage). By identifying the key factor(s), we can guide future developments to ensure clinical impact. Skill in generating muscle signals was assessed via reaction times and signal tracking. To assess the predictability of signal acquisition, we inspected reaction time spread and undesired hand activations. As a measure of device response, we recorded the electromechanical delay between electrode stimulation and the onset of hand movement. Results suggest abstract measures of skill in controlling muscle signals are poorly correlated with performance. Undesired activations of the hand or incorrect responses were correlated with almost all kinematics and gaze measures suggesting unpredictability is a key factor. Significant correlations were also found between several measures of performance and the electromechanical delay; however, unexpectedly, longer electromechanical delays correlated with better performance. Future research should focus on exploring causes of unpredictability, their relative impacts on performance and interventions to address this.

A cognitive style dataset including functional near-infrared spectroscopy, eye-tracking, psychometric and behavioral measures.

The dataset includes data from the triangulated investigation reported in our paper: 'Psychophysiological indices of cognitive style: A triangulated study incorporating neuroimaging, eye-tracking, psychometric and behavioral measures' [1,2]. The data was collected at the Directorate of Psychology & Public Health laboratories at the University of Salford, UK, in 2015 among an English-speaking sample. The dataset includes measures described in the paper including information-processing/cognitive style recorded as Cognitive Style Index [CSI; 3] scores, comparative visual search (CVS) task behavioral measures (reaction time and accuracy), eye-movement data (fixation duration, number of saccades, number of comparative saccades and distance moved) and prefrontal cortex (PFC) oxygenated hemoglobin (oxy-Hb) recorded using functional near-infrared spectroscopy (fNIRS).

Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance.

Studies of the effectiveness of prosthetic hands involve assessing user performance on functional tasks, typically collected in the lab, sometimes combined with self-report of real-world use. In this paper we compare real-world upper limb activity between a group of 20 myoelectric prosthesis users and 20 anatomically intact adults. Activity was measured from wrist-worn accelerometers over a 7-day period. The temporal patterns in upper limb activity are presented and the balance of activity between the two limbs quantified. We also evaluated the prosthesis users' performance on a goal-directed task, characterised using measures including task success rate, completion time, gaze behaviour patterns, and kinematics (e.g. variability and patterns in hand aperture). Prosthesis users were heavily reliant on their intact limb during everyday life, in contrast to anatomically intact adults who demonstrated similar reliance on both upper limbs. There was no significant correlation between the amount of time a prosthesis was worn and reliance on the intact limb, and there was no significant correlation between either of these measures and any of the assessed kinematic and gaze-related measures of performance. We found participants who had been prescribed a prosthesis for longer to demonstrate more symmetry in their overall upper limb activity, although this was not reflected in the symmetry of unilateral limb use. With the exception of previously published case studies, this is the first report of real world upper limb activity in myoelectric prosthesis users and confirms the widely held belief that users are heavily reliant on their intact limb.

Effects of Varied Versus Constant Loading Zones on Muscular Adaptations in Trained Men.

The purpose of this study was to compare the effects of a protocol employing a combination of loading zones vs. one employing a constant medium-repetition loading zone on muscular adaptations in resistance-trained men. 19 trained men (height=176.9±7.0 cm; body mass=83.1±11.8 kg; age=23.3±2.9 years) were randomly assigned to 1 of 2 experimental groups: a constant-rep resistance training (RT) routine (CONSTANT) that trained using 8-12 RM per set, or a varied-rep RT routine (VARIED) that trained with 2-4 RM per set on Day 1, 8-12 RM per set on Day 2, and 20-30 RM on Day 3 for 8 weeks. Results showed that both groups significantly increased markers of muscle strength, muscle thickness, and local muscular endurance, with no differences noted between groups. Effect sizes favored VARIED over CONSTANT condition for elbow flexor thickness (0.72 vs. 0.57), elbow extensor thickness (0.77 vs. 0.48), maximal bench press strength (0.80 vs. 0.57), and upper body muscle endurance (1.91 vs. 1.28). In conclusion, findings indicate that both varied and constant loading approaches can promote significant improvements in muscular adaptations in trained young men.

Exploring visuomotor priming following biological and non-biological stimuli.

Observation of human actions influences the observer's own motor system, termed visuomotor priming, and is believed to be caused by automatic activation of mirror neurons. Evidence suggests that priming effects are larger for biological (human) as opposed to non-biological (object) stimuli and enhanced when viewing stimuli in mirror compared to anatomical orientation. However, there is conflicting evidence concerning the extent of differences between biological and non-biological stimuli, which may be due to stimulus related confounds. Over three experiments, we compared how visuomotor priming for biological and non-biological stimuli was affected over views, over time and when attention to the moving stimulus was manipulated. The results indicated that the strength of priming for the two stimulus types was dependent on attentional location and load. This highlights that visuomotor priming is not an automatic process and provides a possible explanation for conflicting evidence regarding the differential effects of biological and non-biological stimuli.

Does Parkinson's disease affect judgement about another person's action?

The observer's motor system has been shown to be involved in observing the actions of another person. Recent findings suggest that people with Parkinson's disease do not show the same motor facilitatory effects when observing the actions of another person. We studied whether Parkinson's patients were able to make unspeeded judgements about another person's action. Participants were asked to watch video clips of an actor lifting a box containing different weights (100, 200, 300 or 400 g) and to guess the weight that was being lifted on a 9-point scale. We compared the performance of 16 patients with PD with 16 healthy age-matched controls. Both groups were able to do the task, showing a significant relationship between the real weight and the guessed weight, albeit with a tendency to overestimate the lowest weight and underestimate the heaviest weight. The PD patients, however, showed a reduced slope value. These results show that despite their own motor deficits, PD patients are still able to judge the weight being lifted by another person, albeit with a slight reduction in accuracy. Further research will be required to determine whether PD patients use a motor simulation or a visual compensatory strategy to achieve this.

Differences in folylpolyglutamate synthetase and dihydrofolate reductase expression in human B-lineage versus T-lineage leukemic lymphoblasts: mechanisms for lineage differences in methotrexate polyglutamylation and cytotoxicity.

Cellular accumulation of methotrexate polyglutamates (MTXPGs) is recognized as an important determinant of the cytotoxicity and selectivity of methotrexate in acute lymphoblastic leukemia (ALL). We identified a significantly lower cellular accumulation of MTXPGs in T-lineage versus B-lineage lymphoblasts in children with ALL, which is consistent with the worse prognosis of T-lineage ALL when treated with conventional antimetabolite-based therapy. Maximum MTXPG accumulation in leukemic blasts in vivo was 3-fold greater in lymphoblasts of children with B-lineage ALL (129 children) compared with those with T-lineage ALL (20 children) (p < 0.01) and was characterized by a saturable (Emax) model in both groups. The human leukemia cell lines NALM6 (B-lineage) and CCRF/CEM (T-lineage) were used to assess potential mechanisms for these lineage differences in MTX accumulation, revealing i) greater total and long-chain MTXPG accumulation in NALM6 over a wide range of methotrexate concentrations (0.2-100 microM), ii) saturation of MTXPG accumulation in both cell lines, with a higher maximum (Emax in NALM6, iii) 3-fold higher constitutive FPGS mRNA expression and enzyme activity in NALM6 cells, iv) 2-fold lower levels of DHFR mRNA and protein in NALM6 cells, and v) 4-6 fold lower extracellular MTX concentration and 2-fold lower intracellular MTXPG concentration to produce equivalent cytotoxicity (LC50) in NALM6 versus CEM. There was a significant relationship between FPGS mRNA and enzyme activity in lymphoblasts from children with newly diagnosed ALL, and blast FPGS mRNA and activity increased after methotrexate treatment. These data indicate higher FPGS and lower DHFR levels as potential mechanisms contributing to greater MTXPG accumulation and cytotoxicity in B-lineage lymphoblasts.

A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase.

Thiopurine S-methyltransferase (TPMT; S-adenosyl-L-methionine:thiopurine S-methyltransferase, EC 2.1.1.67) activity exhibits genetic polymorphism, with approximately 0.33% of Caucasians and African-Americans inheriting TPMT deficiency as an autosomal recessive trait. To determine the molecular genetic basis for this polymorphism, we cloned the TPMT cDNA from a TPMT-deficient patient who had developed severe hematopoietic toxicity during mercaptopurine therapy. Northern blot analysis of RNA isolated from leukocytes of the deficient patient demonstrated the presence of TPMT mRNAs of comparable size to that in subjects with high TPMT activity. Sequencing of the mutant TPMT cDNA revealed a single point mutation (G238-->C), leading to an amino acid substitution at codon 80 (Ala80-->Pro). When assessed in a yeast heterologous expression system, this mutation led to a 100-fold reduction in TPMT catalytic activity relative to the wild-type cDNA, despite a comparable level of mRNA expression. A mutation-specific PCR amplification method was developed and used to detect the G238-->C mutation in genomic DNA of the propositus and her mother. This inactivating mutation in the human TPMT gene provides insights into the genetic basis for this inherited polymorphism in drug metabolism.

Therapeutic drug monitoring in cancer management.

Several anticancer drugs display characteristics that make them suitable candidates for therapeutic drug monitoring (TDM), including substantial pharmacokinetic variability and a narrow therapeutic index. However, concentration-effect relationships (pharmacodynamics) of most antineoplastic agents have not been well defined, thus limiting the widespread clinical application of TDM for cancer chemotherapy. Strategic incorporation of pharmacokinetic studies during phase I-III clinical trials should facilitate the identification of concentration-effect relationships and the definition of clinically useful levels of treatment intensity. We review representative clinical studies that have defined pharmacodynamic relationships for methotrexate, teniposide, etoposide, carboplatin, and mercaptopurine. Given that TDM has impacted positively on the clinical use of many drugs belonging to other therapeutic classes, and that pharmacodynamic correlations have been identified in several recent studies of anticancer drugs, we consider implementation of TDM a rational strategy for optimizing the use of selected antineoplastics.