Size-tuneable nanometric MRI contrast agents for the imaging of molecular weight dependent transport processes

Purpose: To evaluate size-tuneable nanomeric glycol-chitosan-DTPA-Gd conjugates as MRI contrast agents for the imaging of molecular weight (MW) dependent transport processes. Material & Methods: Glycol chitosans (GC) – DTPA conjugates of precisely controlled MWs were synthesised and evaluated in mice against Gd-DTPA using times series of high-resolution MRI images of trunk, head, and xenograft flank tumours. All animal studies were approved by the local ethics committee and the UK authorities. Results: GC-DTPA modification ratio was one DTPA per 3.9 – 5.13 of GC monomers. GC-DTAPGd provided overall superior contrast compared to Gd-DTPA with the duration of the enhancement depending on MW (≥ 1h for 40kD). Kidneys showed early enhancement also in the renal pelvis suggesting renal elimination. Imaging of the head with GC-DTPA-Gd allowed detailed anatomical identification of specific blood vessels in particular with the high MW agent. Sequential high-resolution isotropic imaging of established A431 xenograft flank tumours with DTPA-Gd and GC-DTPA-Gd demonstrated that the initial delivery of the contrast agents was well correlated with blood supply. Subsequent tissue transport was primarily by diffusion and was limited by molecular weight. The data also highlight the role of heterogeneity in CA distribution that was again more prominent for the high MW agent. Conclusion: GC-DTPA-Gd with identical physical chemical properties but precisely controlled MW allow isotropic high-resolution three-dimensional imaging of molecular weight dependent transport processes which could potentially lead to clinical biomarkers for molecular weight dependent drug transport and support selection of suitable tumour models for pre-clinical development

Coupling of upper and lower limb pattern generators during human crawling at different arm/leg speed combinations

A crawling paradigm was performed by healthy adults to examine inter-limb coupling patterns and to understand how central pattern generators (CPGs) for the upper and lower limbs are coordinated. Ten participants performed hands-and-feet crawling on two separate treadmills, one for the upper limbs and another one for the lower limbs, the speed of each of them being changed independently. A 1:1 frequency relationship was often maintained even when the treadmill speed was not matched between the upper and lower limbs. However, relative stance durations in the upper limbs were only affected by changes of the upper limb treadmill speed, suggesting that although absolute times are adjusted, the relative proportions of stances and swing do not adapt to changes in lower limb treadmill speeds. With large differences between treadmill speeds, changes in upper and lower limb coupling ratio tended to occur when the upper limbs stepped at slower speeds than the lower limbs, but more rarely the other way around. These findings are in sharp contrast with those in the cat, where forelimbs always follow the rhythm of the faster moving hindlimbs. However, the fact that an integer frequency ratio is often maintained between the upper and lower limbs supports evidence of coupled CPG control. We speculate that the preference for the upper limb to decrease step frequency at lower speeds in humans may be due to weaker ascending propriospinal connections and/or a larger influence of cortical control on the upper limbs which allows for an overriding of spinal CPG control

Locomotor-like leg movements evoked by rhythmic arm movements in humans

Motion of the upper limbs is often coupled to that of the lower limbs in human bipedal locomotion. It is unclear, however, whether the functional coupling between upper and lower limbs is bi-directional, i.e. whether arm movements can affect the lumbosacral locomotor circuitry. Here we tested the effects of voluntary rhythmic arm movements on the lower limbs. Participants lay horizontally on their side with each leg suspended in an unloading exoskeleton. They moved their arms on an overhead treadmill as if they walked on their hands. Hand-walking in the antero-posterior direction resulted in significant locomotor-like movements of the legs in 58% of the participants. We further investigated quantitatively the responses in a subset of the responsive subjects. We found that the electromyographic (EMG) activity of proximal leg muscles was modulated over each cycle with a timing similar to that of normal locomotion. The frequency of kinematic and EMG oscillations in the legs typically differed from that of arm oscillations. The effect of hand-walking was direction specific since medio-lateral arm movements did not evoke appreciably leg air-stepping. Using externally imposed trunk movements and biomechanical modelling, we ruled out that the leg movements associated with hand-walking were mainly due to the mechanical transmission of trunk oscillations. EMG activity in hamstring muscles associated with hand-walking often continued when the leg movements were transiently blocked by the experimenter or following the termination of arm movements. The present results reinforce the idea that there exists a functional neural coupling between arm and legs

Experienced tutors' deployment of thinking skills and what might be entailed in enhancing such skills

In the context of research that reports weaknesses in adults' critical thinking skills, the primary aim was to examine adults' use of critical thinking skills that are described in taxonomies and to identify areas for development. Position papers written by an opportunity sample of 32 experienced adult educators formed the data for a descriptive sample survey design intended to reveal participants' use of critical thinking skills. Each 6000-word paper was written during a development programme that supported such skills. A content analysis of the papers revealed that when participants drew on personal and published ideas about learning to derive their proposals for change, they accepted the ideas uncritically, thereby implying that they might find it difficult to help learners to examine ideas critically. The evidence supports research that implies that critical thinking skills are unlikely to develop unless overall course design privileges the development of epistemological understanding (King and Kitchener 1994, Kuhn 1999). A fundamental assumption underlying the study is that this understanding influences effective citizenship and personal development, as well as employability. A proposition that merits attention in future research is that the development of epistemological understanding is largely neglected in current curricula in formal post-16 education

Helping education undergraduates to use appropriate criteria for evaluating accounts of motivation

The aim of the study was to compare students in a control group with those in a treatment group with respect to evaluative comments on psychological accounts of motivation. The treatment group systematically scrutinized the nature and interpretation of evidence that supported different accounts, and the assumptions, logic, coherence and clarity of accounts. Content analysis of 74 scripts (using three categories) showed that the control group students made more assertions than either evidential or evaluative points, whereas the treatment group used evaluative statements as often as they used assertion. The findings provide support for privileging activities that develop understanding of how knowledge might be contested, and suggest a need for further research on pedagogies to serve this end. The idea is considered that such understanding has a pivotal role in the development of critical thinking

Representing addition and subtraction : learning the formal conventions

The study was designed to test the effects of a structured intervention in teaching children to represent addition and subtraction. In a post-test only control group design, 90 five-year-olds experienced the intervention entitled Bi-directional Translation whilst 90 control subjects experienced typical teaching. Post-intervention testing showed some significant differences between the two groups both in terms of being able to effect the addition and subtraction operations and in being able to determine which operation was appropriate. The results suggest that, contrary to historical practices, children's exploration of real world situations should precede practice in arithmetical symbol manipulation

The significance of motivation in student-centred learning : a reflective case study

The theoretical underpinnings of student-centred learning suggest motivation to be an integral component. However, lack of clarification of what is involved in motivation in education often results in unchallenged assumptions that fail to recognise that what motivates some students may alienate others. This case study, using socio-cognitive motivational theory to analyse previously collected data, derives three fuzzy propositions which, collectively, suggest that motivation interacts with the whole cycle of episodes in the teachinglearning process. It argues that the development of the higherlevel cognitive competencies that are implied by the term, student-centred learning, must integrate motivational constructs such as goal orientation, volition, interest and attributions into pedagogical practices

Measurement of the angle, temperature and flux of fast electrons emitted from intense laser-solid interactions

High-intensity laser-solid interactions generate relativistic electrons, as well as high-energy (multi-MeV) ions and X-rays. The directionality, spectra and total number of electrons that escape atarget-foil is dependent on the absorption, transport and rear-side sheath conditions. Measuring the electrons escaping the target will aid in improving our understanding of these absorption processes and the rear-surface sheath fields that retard the escaping electrons and accelerate ions via the target normal sheath acceleration (TNSA) mechanism. A comprehensive Geant4 study was performed to help analyse measurements made with a wrap-around diagnostic that surrounds the target and uses differential filtering with a FUJI-film image plate detector. The contribution of secondary sources such as X-rays and protons to the measured signal have been taken into account to aid in the retrieval of the electron signal. Angular and spectral data from a high-intensity laser-solid interaction are presented and accompanied by simulations. The total number of emitted electrons has been measured as 2.6 × 1013 with an estimated total energy of 12 ± 1 J from a 100 mu;m Cu target with140 J of incident laser energy during a 4 × 1020 W cm-2 interaction