The Lesioned Spinal Cord Is a "New" Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury

Validity and repeatability of three in-shoe pressure measurement systems

In-shoe pressure measurement devices are used in research and clinic to quantify plantar foot pressures. Various devices are available, differing in size, sensor number and type; therefore accuracy and repeatability. Three devices (Medilogic, Tekscan and Pedar) were examined in a 2 day×3 trial design, quantifying insole response to regional and whole insole loading. The whole insole protocol applied an even pressure (50-600kPa) to the insole surface for 0-30s in the Novel TruBlue™ device. The regional protocol utilised cylinders with contact surfaces of 3.14 and 15.9cm(2) to apply pressures of 50 and 200kPa. The validity (% difference and Root Mean Square Error: RMSE) and repeatability (Intra-Class Correlation Coefficient: ICC) of the applied pressures (whole insole) and contact area (regional) were outcome variables. Validity of the Pedar system was highest (RMSE 2.6kPa; difference 3.9%), with the Medilogic (RMSE 27.0kPa; difference 13.4%) and Tekscan (RMSE 27.0kPa; difference 5.9%) systems displaying reduced validity. The average and peak pressures demonstrated high between-day repeatability for all three systems and each insole size (ICC≥0.859). The regional contact area % difference ranged from -97 to +249%, but the ICC demonstrated medium to high between-day repeatability (ICC≥0.797). Due to the varying responses of the systems, the choice of an appropriate pressure measurement device must be based on the loading characteristics and the outcome variables sought. Medilogic and Tekscan were most effective between 200 and 300kPa; Pedar performed well across all pressures. Contact area was less precise, but relatively repeatable for all systems

An exploratory qualitative study of health professional perspectives on clinical outcomes in UK orthotic practice

Background: Despite potential savings to the National Health Service, the collection of data on outcomes of NHS orthotic services is patchy. Indeed, several reports into orthotic services in the UK have reported a lack of data relating to outcomes of care and highlighted the need to routinely measure outcomes to demonstrate efficacy of services. Whilst a previous study provided an overview of the use of outcome measures in orthotic practice and identified some barriers to their use, further questions emerged. Hence, this qualitative study aimed to explore orthotists’ opinions and personal experiences on the influences on outcomes, how appropriate and relevant outcomes can be measured and also how barriers to the use of outcome measures can be overcome. Methods: Following a review of the literature, an initial advisory group informed semi-structured questions. These were used to create dialogue in a focus group of 12 orthotists. Data from the focus group was transcribed verbatim and analysed using thematic analysis, creating themes and subthemes for discussion. Results: The setting of realistic and agreed goals through managing expectations, compromise and patient education/information were seen as factors that could inform and improve outcomes. Barriers to the collection of outcome measures were associated with inadequate technology to manage the data, lack of time to complete them, lack of training in them and difficulties selecting appropriate outcome measures for patients with complex problems managed by different health professionals. The participants discussed ways of addressing these barriers, such as the use of ‘snapshots’ and delegation of data collection. Conclusions: This study has revealed that measuring outcomes is considered to be an important activity. In order to achieve good outcomes, it is important to address patient expectations, discuss and establish joint goals for care at the outset and inform and include patients in the decision-making process. The identified barriers to measuring outcomes can be overcome with the solutions revealed by these participants. Hence, this study has contributed to current knowledge which has relevance for clinical practice and may provide the theoretical basis for future research

Cell cycle responses to Topoisomerase II inhibition: Molecular mechanisms and clinical implications.

DNA Topoisomerase IIA (Topo IIA) is an enzyme that alters the topological state of DNA and is essential for the separation of replicated sister chromatids and the integrity of cell division. Topo IIA dysfunction activates cell cycle checkpoints, resulting in arrest in either the G2-phase or metaphase of mitosis, ultimately triggering the abscission checkpoint if non-disjunction persists. These events, which directly or indirectly monitor the activity of Topo IIA, have become of major interest as many cancers have deficiencies in Topoisomerase checkpoints, leading to genome instability. Recent studies into how cells sense Topo IIA dysfunction and respond by regulating cell cycle progression demonstrate that the Topo IIA G2 checkpoint is distinct from the G2-DNA damage checkpoint. Likewise, in mitosis, the metaphase Topo IIA checkpoint is separate from the spindle assembly checkpoint. Here, we integrate mechanistic knowledge of Topo IIA checkpoints with the current understanding of how cells regulate progression through the cell cycle to accomplish faithful genome transmission and discuss the opportunities this offers for therapy

Improving the distances of post-AGB objects in the Milky Way

Conference Theme: Physics and Chemistry of the Late Stages of Stellar EvolutionPost-AGB (PAGB) stars are short-lived, low-intermediate mass objects transitioning from the asymptotic giant branch (AGB) to the white dwarf (WD) phase. These objects are characterised by a constant, core-mass dependent luminosity and a large infrared excess from the dusty envelope ejected at the top of the AGB. PAGB stars provide insights into the evolution of their direct descendants, planetary nebulae (PNe). Calculation of physical characteristics of PAGB are dependent on accurately determined distances scarcely available in the literature. Using the Torun catalogue for PAGB objects, supplemented with archival data, we have determined distances to the known population of Galactic PAGB stars. This is by modelling their spectral energy distributions (SED) with black bodies and numerically integrating over the entire wavelength range to determine the total integrated object flux. For most PAGB stars we assumed their luminosities are based on their positional characteristics and stellar evolution models. RV Tauri stars however are known to follow a period-luminosity relation (PLR) reminiscent of type-2 Cepheids. For these variable PAGB stars we determined their luminosities via the PLR and hence their distances. This allows us to overcome the biggest obstacle to characterising these poorly understood objects that play a vital part in Galactic chemical enrichment.postprin

headspace - Australia's innovation in youth mental health: who are the clients and why are they presenting?

OBJECTIVES: To provide the first national profile of the characteristics of young people (aged 12-25 years) accessing headspace centre services - the Australian Government's innovation in youth mental health service delivery - and investigate whether headspace is providing early service access for adolescents and young adults with emerging mental health problems. DESIGN AND PARTICIPANTS: Census of all young people accessing a headspace centre across the national network of 55 centres comprising a total of 21 274 headspace clients between 1 January and 30 June 2013. MAIN OUTCOME MEASURES: Reason for presentation, Kessler Psychological Distress Scale, stage of illness, diagnosis, functioning. RESULTS: Young people were most likely to present with mood and anxiety symptoms and disorders, self-reporting their reason for attendance as problems with how they felt. Client demographic characteristics tended to reflect population-level distributions, although clients from regional areas and of Aboriginal and Torres Strait Islander background were particularly well represented, whereas those who were born outside Australia were underrepresented. CONCLUSION: headspace centres are providing a point of service access for young Australians with high levels of psychological distress and need for care in the early stages of the development of mental disorder

Statistical comparison of InSAR tropospheric correction techniques

Correcting for tropospheric delays is one of the largest challenges facing the interferometric synthetic aperture radar (InSAR) community. Spatial and temporal variations in temperature, pressure, and relative humidity create tropospheric signals in InSAR data, masking smaller surface displacements due to tectonic or volcanic deformation. Correction methods using weather model data, GNSS and/or spectrometer data have been applied in the past, but are often limited by the spatial and temporal resolution of the auxiliary data. Alternatively a correction can be estimated from the interferometric phase by assuming a linear or a power-law relationship between the phase and topography. Typically the challenge lies in separating deformation from tropospheric phase signals. In this study we performed a statistical comparison of the state-of-the-art tropospheric corrections estimated from the MERIS and MODIS spectrometers, a low and high spatial-resolution weather model (ERA-I and WRF), and both the conventional linear and new power-law empirical methods. Our test-regions include Southern Mexico, Italy, and El Hierro. We find spectrometers give the largest reduction in tropospheric signal, but are limited to cloud-free and daylight acquisitions. We find a ~ 10–20% RMSE increase with increasing cloud cover consistent across methods. None of the other tropospheric correction methods consistently reduced tropospheric signals over different regions and times. We have released a new software package called TRAIN (Toolbox for Reducing Atmospheric InSAR Noise), which includes all these state-of-the-art correction methods. We recommend future developments should aim towards combining the different correction methods in an optimal manner

Estimating the material properties of heel pad sub-layers using inverse finite element analysis

Detailed information about the biomechanical behaviour of plantar heel pad tissue contributes to our understanding of load transfer when the foot impacts the ground. The objective of this work was to obtain the hyperelastic and viscoelastic material properties of heel pad sub-layers (skin, micro-chamber and macro-chamber layers) in-vivo. An anatomically detailed 3D Finite Element model of the human heel was used to derive the sub-layer material properties. A combined ultrasound imaging and motorised platform system was used to compress heel pad and to create input data for the Finite Element model. The force-strain responses of the heel pad and its sub-layers under slow compression (5mm/s) and rapid loading-hold-unloading cycles (225mm/s), were measured and hyperelastic and viscoelastic properties of the three heel pad sub-layers were estimated by the model. The loaded (under ~315N) thickness of the heel pad was measured from MR images and used for hyperelastic model validation. The capability of the model to predict peak plantar pressure was used for further validation. Experimental responses of the heel pad under different dynamic loading scenarios (loading-hold-unloading cycles at 141mm/s and sinusoidal loading with maximum velocity of 300mm/s) were used to validate the viscoelastic model. Good agreement was achieved between the predicted and experimental results for both hyperelastic (<6.4% unloaded thickness, 4.4% maximum peak plantar pressure) and viscoelastic (Root Mean Square errors for loading and unloading periods <14.7%, 5.8% maximum force) simulations. This paper provides the first definition of material properties for heel pad sub-layers by using in-vivo experimental force-strain data and an anatomically detailed 3D Finite Element model of the heel

Inverse modulation of motor neuron cellular and synaptic properties can maintain the same motor output

Although often examined in isolation, a single neuromodulator typically has multiple cellular and synaptic effects. Here, we have examined the interaction of the cellular and synaptic effects of 5-HT in the lamprey spinal cord. 5-HT reduces the amplitude of glutamatergic synaptic inputs and the slow post-spike afterhyperpolarization (sAHP) in motor neurons. We examined the interaction between these effects using ventral root activity evoked by stimulation of the spinal cord. While 5-HT reduced excitatory glutamatergic synaptic inputs in motor neurons to approximately 60% of control, ventral root activity was not significantly affected. The reduction of the sAHP by 5-HT increased motor neuron excitability by reducing spike frequency adaptation, an effect that could in principle have opposed the reduction of the excitatory synaptic input. Support for this was sought by reducing the amplitude of the sAHP by applying the toxin apamin before 5-HT application. In these experiments, 5-HT reduced the ventral root response, presumably because the reduction of the synaptic input now dominated. This was supported by computer simulations that showed that the motor output could be maintained over a wide range of synaptic input values if they were matched by changes in postsynaptic excitability. The effects of 5-HT on ventral root responses were altered by spinal cord lesions: 5-HT significantly increased ventral root responses in animals that recovered good locomotor function, consistent with a lesion-induced reduction in the synaptic effects of 5-HT, which thus biases its effects to the increase in motor neuron excitability.Non