Repeatability of the Oxford Foot Model: Comparison of a team of assessors with different backgrounds and no prior experience of the Oxford Foot Model.

RESEARCH QUESTION: What is the intra- and inter-assessor error of the Oxford Foot Model (OFM) during healthy adult walking when applied by three assessors with different professional backgrounds and lower limb marker placement experience, not native to the originators of the model and with no prior clinical experience of the model? BACKGROUND: No previous OFM studies have examined the repeatability of more than two assessors with different backgrounds, and many of the studies have been conducted by the model originators METHODS: The OFM was applied to ten healthy adults on three separate occasions by three different assessors with varied professional experience and no prior involvement with the OFM (other than local training). Participants walked at self-selected speeds and intra/inter assessor error was calculated using the SEM + 95% upper confidence limit. RESULTS: Inter-assessor errors ranged from 2.2° to 5.5° whereas intra-assessor errors fell between 1.8° and 5.5°. The error difference between assessors over the same joint angle varied from 0.4° (hindfoot/tibia dorsiflexion) to 1.5° (hindfoot/tibia inversion). The percentage of error to total range of motion varied from 11% (hindfoot/tibia dorsiflexion) to 126% (forefoot/hindfoot adduction). SIGNIFICANCE: Based on commonly used recommendations, the OFM is a largely repeatable tool for measuring foot kinematics during healthy adult walking when applied by assessors with no prior OFM experience, varied experience and not native to the model originators. Intra-assessor error was lower for assessors with prior anatomical knowledge and significant lower limb marker placement experience. The proportion of inter-assessor error to movement exceeded 50% of the total range of motion for four movements, notably forefoot/hindfoot adduction (126%). As such, this movement cannot be recommended as an outcome measure. Inter- and intra-assessor error, specific to each laboratory, should be considered, along with the proportion of error to range of motion when interpreting patient data.

The conventional gait model, an open-source implementation that reproduces the past but prepares for the future.

BACKGROUND: The Conventional Gait Model (CGM), known by a variety of different names, is widely used in clinical gait analysis. We present pyCGM2, an open-source implementation of the CGM with two versions. The first, CGM1.0, is a clone of Vicon Plug In Gait (PiG) with all its variants. CGM1.0 provides a platform to test the effect of modifications to the CGM on data collected and processed retrospectively or to provide backward compatibility. The second version, CGM1.1, offers some practical modifications and includes three well documented improvements. RESEARCH QUESTION: How do improvements of the conventional gait model affect joint kinematics and kinetics? METHOD: The practical modifications include the possibility to use a medial knee epicondyle marker, during static calibration only, to define the medio-lateral axis of the femur in place of the knee alignment device. The three improvements correspond to the change of pelvis angle decomposition sequence, the adoption of a single tibia coordinate system, and the default decomposition of the joint moments in the joint coordinate system. We validated the outputs of version CGM1.0 against Vicon-PiG, and estimated the effect of the modifications included in version CGM1.1 using gait data collected in 16 healthy participants. RESULTS: Kinematics and kinetics of CGM1.0 were superimposed with that of Vicon-PiG, with root mean square differences less than 0.04° for kinematics and less than 0.05 N.m.kg-1 for kinetics. SIGNIFICANCE: The differences between the CGM1.1 and CGM1.0 were minimal in the healthy participant cohort but we discussed the expected difference in participants with different gait pathologies. We hope that the pyCGM2 will facilitate the systematic testing and the use of improved processing methods for the conventional gait model.

The effect on conventional gait model kinematics and kinetics of hip joint centre equations in adult healthy gait.

The Conventional Gait Model (CGM) needs to benefit from large investigations on localization of the hip joint centre (HJC). Incorrect positions from the native equations were demonstrated (Sangeux et al., 2014; Harrington et al., 2007). More accurate equations were proposed but their impact on kinematics and kinetic CGM outputs was never evaluated. This short communication aims at examining if adoption of new HJC equations would alter standard CGM outputs. Sixteen able bodied participants underwent a full 3-D optoelectronic gait analysis followed by a 3-D ultrasound localization of their hips. Data were processed through the open source python package pyCGM2 replicating kinematic and kinetic processing of the native CGM. Compared with 3D ultrasound location, Hara equations improved the accuracy of sagittal plane kinematics (0.6°) and kinetics (0.02 N m kg-1) for the hip. The worst case participant exhibited Harrington's equations reached a deviation of 3° for the sagittal kinematics. In the coronal plane, Hara and Harrington equations presented similar differences (1°) for the hip whilst Davis equations had the largest deviation for hip abduction (2.7°) and hip abductor moment (0.10 N m kg-1). Both Harrington and Hara equations improved the CGM location of the HJC. Hara equations improved results in the sagittal plane, plus utilise a single anthropometrics measurement, leg length, that may be more robust. However, neither set of equations had significant effect on kinematics. We reported some effects on kinetics, particularly in the coronal plane, which warrant caution in interpreting outputs using different sets of equations.

The conventional gait model, an open-source implementation that reproduces the past but prepares for the future.

BACKGROUND: The Conventional Gait Model (CGM), known by a variety of different names, is widely used in clinical gait analysis. We present pyCGM2, an open-source implementation of the CGM with two versions. The first, CGM1.0, is a clone of Vicon Plug In Gait (PiG) with all its variants. CGM1.0 provides a platform to test the effect of modifications to the CGM on data collected and processed retrospectively or to provide backward compatibility. The second version, CGM1.1, offers some practical modifications and includes three well documented improvements. RESEARCH QUESTION: How do improvements of the conventional gait model affect joint kinematics and kinetics? METHOD: The practical modifications include the possibility to use a medial knee epicondyle marker, during static calibration only, to define the medio-lateral axis of the femur in place of the knee alignment device. The three improvements correspond to the change of pelvis angle decomposition sequence, the adoption of a single tibia coordinate system, and the default decomposition of the joint moments in the joint coordinate system. We validated the outputs of version CGM1.0 against Vicon-PiG, and estimated the effect of the modifications included in version CGM1.1 using gait data collected in 16 healthy participants. RESULTS: Kinematics and kinetics of CGM1.0 were superimposed with that of Vicon-PiG, with root mean square differences less than 0.04° for kinematics and less than 0.05 N.m.kg-1 for kinetics. SIGNIFICANCE: The differences between the CGM1.1 and CGM1.0 were minimal in the healthy participant cohort but we discussed the expected difference in participants with different gait pathologies. We hope that the pyCGM2 will facilitate the systematic testing and the use of improved processing methods for the conventional gait model.

Glucose and the wandering mind: not paying attention or simply out of fuel?

RATIONALE/OBJECTIVES: The impact of raising glycaemia by ingestion of a glucose drink has revealed cognitive facilitation, particularly for memory and attention. This study aimed to extend current knowledge by examining, for the first time, whether glucose load also moderates task-related (TRT) and task-unrelated thoughts (TUT) during activities that vary in their requirement for sustained attention. METHOD: A 2 (25 g glucose vs. placebo) × 2 (fast vs. slow version of the Sustained Attention to Response Task (SART)) repeated measures, counterbalanced design was used with 16 healthy adults. Self-report questionnaires probed participants' levels of TRT and TUT during SART performance. Prior to testing, the Short Imaginal Processes Inventory (SIPI) was also administered to help pinpoint the nature of thought processes during the task before and after treatment. RESULTS: Analysis of variance revealed no significant effect of treatment; however, we report a pattern of results that is consistent with glucose facilitation effects on task accuracy for more demanding attention tasks (d = 0.56). Additionally, glucose improved the monitoring and task reflection as measured by TRT (d = 0.33) in the more demanding task but no effect on TUT. Probing the nature of thought processes further, we also report two novel correlations (in the placebo) between fears of failure (indexed by the SIPI) and the number of TUT episodes and perceived poor attention control (indexed by the SIPI) and number of TUT and speculate that glucose may act to buffer against TUT episodes under externally demanding situations. CONCLUSIONS: These data extend previous research examining the glucose facilitation effect to the processing of internal thought processes.

B vitamins and cognitive performance in older adults: review.

A copious amount of scientific scrutiny has been dedicated to documenting typical and atypical human ageing, with a substantial body of work focusing upon the impact of lifestyle choices. One such lifestyle choice is that of diet and, in particular, micronutrient ingestion. Epidemiological studies have reported positive associations between B vitamin status and cognitive function, including negative associations between biological markers (i.e., homocysteine) of dysregulated one-carbon metabolism and cognitive function. This has led to a surge of randomised control trials (RCTs) investigations into B vitamin therapy. However, results have continuingly failed to show beneficial behavioural effects. Despite this, results reliably show treatment-related increases in B vitamin level and decreases in homocysteine level-both of which have been identified as risk factors for atypical ageing. In this paper we argue that it would be premature to conclude that B vitamin therapy has no potential and that more research is needed to systematically investigate the optimal dose, the therapeutic "window," and individual differences in therapy responders and nonresponders. We start with a brief look at one-carbon metabolism and then consider the evidence from epidemiological studies and RCTs in relation to three specific B vitamins: folic acid (B9), pyridoxine (B6), and cobamides (B12).

The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12.

Interleukin (IL)-23 is a member of the IL-12 family of heterodimeric cytokines, comprised of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. We have demonstrated previously that adenoviral-mediated, intratumoral delivery of IL-23 (Ad.IL-23) was able to induce systemic antitumor immunity. Here we demonstrate that Ad.IL-23 requires endogenous IL-12 for conferring an antitumor effect after adenoviral-mediated, intratumoral delivery. In contrast, Ad.IL-12 does not require IL-23 for its antitumor effects although endogenous IL-23 appears important for induction of systemic antitumor immunity by IL-12. However, despite the requirement for endogenous IL-12, co-delivery of IL-23 and IL-12 does not provide even an additive local or systemic antitumor effect, regardless of the dose. We further demonstrate that although the use of a single-chain IL-23 (scIL-23) results in higher level of expression and a more pronounced IL-23-mediated antitumor effect, there is still no synergy with IL-12. These results demonstrate that although significant antitumor effects are achieved by intratumoral injection of adenovirus expressing either scIL-23 or IL-12 alone and that IL-23 requires endogenous IL-12 for maximum antitumor benefit, the combined use of these cytokines provides no additive or synergistic effect.

Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response.

Interleukin 23 (IL-23) is a member of the IL-12 family of heterodimeric cytokines, composed of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. IL-23 has been shown to possess potent antitumor activities in several establishment models of cancer and a few therapeutic models, but the efficacy of local, adenoviral-mediated expression of IL-23 in established tumors has yet to be investigated. Here we have examined the antitumor activity of adenovirally delivered IL-23 in a day-7 MCA205 murine fibrosarcoma tumor model. Three intratumoral injections of adenovirus expressing IL-23 (Ad.IL-23) significantly increased animal survival and resulted in complete rejection of 40% of tumors, with subsequent generation of protective immunity and MCA205-specific cytotoxic T lymphocytes. In addition, we have shown that the antitumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but dependent on interferon-gamma, CD4(+) and CD8(+) T cells. These results demonstrate that direct intratumoral injection of adenovirus expressing IL-23 results in enhanced survival, tumor eradication and generation of protective immunity by generation of a Th1-type immune response.

Improved cognitive performance and mental fatigue following a multi-vitamin and mineral supplement with added guaraná (Paullinia cupana).

Guaraná (Paullinia cupana) extracts are most commonly used in Western markets as putatively psychoactive food and drink additives. This double-blind, randomised, placebo-controlled, parallel groups study assessed the acute effects of either a vitamin/mineral/guaraná supplement or placebo drink in 129 healthy young adults (18-24 years). Participants completed a 10min version of the Cognitive Demand Battery (comprising: Serial 3s and Serial 7s subtraction tasks, a Rapid Visual Information Processing (RVIP) task, 'mental fatigue' scale). Thirty minutes following their drink participants made six consecutive completions of the battery (i.e. 60 min). The vitamin/mineral/guaraná combination resulted in improved task performance, in comparison to placebo, in terms of both increased speed and accuracy of performing the RVIP task throughout the post-dose assessment. The increase in mental fatigue associated with extended task performance was also attenuated by the supplement. This research supports previous findings demonstrating guaraná's cognition enhancing properties and provides evidence that its addition to a multi-vitamin-mineral supplement can improve cognitive performance and reduce the mental fatigue associated with sustained mental effort.

The glycaemic effects of single doses of Panax ginseng in young healthy volunteers.

The results of two acute placebo-controlled, double-blind cross-over studies assessing the effect of Panax ginseng (G115) on blood glucose levels are reported. In study 1, thirty participants received three treatments: placebo; 200 mg G115; 400 mg G115. In study 2, twenty-seven participants received four treatments: placebo (0 mg ginseng and 30 mg saccharin); ginseng (200 mg ginseng and 30 mg saccharin); placebo-glucose (0 mg ginseng and 25 g oral glucose); ginseng-glucose (200 mg ginseng and 25 g oral glucose). Blood glucose levels were measured at baseline (at 09.00 hours after an overnight fast) and then 60, 90 (study 1 only) and 120 min post-dose. Both studies demonstrated that G115 alone significantly lowers fasting blood glucose levels. Conversely, in study 2 there was a significant drink x ginseng interaction suggesting opposing glycaemic effects of ginseng under fasting and raised blood glucose conditions. These data have implications for the use of ginseng in individuals with poor gluco-regulation.

MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.

In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on "prefrontal" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.

The influence of patient size on patient doses in cardiology.

In cardiology and interventional radiology, areas that contribute large components to medical radiation exposure, a major source of variation in patient dose is the variation in complexity between cases for nominally identical procedures. In patient dose surveys, this variation tends to mask that due to patient size. The effect of applying a previously defined size correction to cardiology patient dose-area product (DAP) records was investigated. The correction method uses the experimentally determined relationship between patient diameter and DAP to derive a factor to convert DAP to that which would be expected had the patient been similar in size to ICRP Reference Man. The size correction was found to greatly reduce the residual correlation of DAP with patient weight. An implication of this finding is that data collection for the setting of diagnostic reference levels in cardiology can be performed for all patients rather than just 'standard-sized' patients.

Is patient size important in dose determination and optimization in cardiology?

Patient dose determination and optimization have become more topical in recent years with the implementation of the Medical Exposures Directive into national legislation, the Ionising Radiation (Medical Exposure) Regulations. This legislation incorporates a requirement for new equipment to provide a means of displaying a measure of patient exposure and introduces the concept of diagnostic reference levels. It is normally assumed that patient dose is governed largely by patient size; however, in cardiology, where procedures are often very complex, the significance of patient size is less well understood. This study considers over 9000 cardiology procedures, undertaken throughout the north of England, and investigates the relationship between patient size and dose. It uses simple linear regression to calculate both correlation coefficients and significance levels for data sorted by both room and individual clinician for the four most common examinations, left ventrical and/or coronary angiography, single vessel stent insertion and single vessel angioplasty. This paper concludes that the correlation between patient size and dose is weak for the procedures considered. It also illustrates the use of an existing method for removing the effect of patient size from dose survey data. This allows typical doses and, therefore, reference levels to be defined for the purposes of dose optimization.